PMID- 23143976
TI - Regulation of tumor cell dormancy by tissue microenvironments and autophagy.
AB - The development of metastasis is the major cause of death in cancer patients. In
certain instances, this occurs shortly after primary tumor detection and
treatment, indicating these lesions were already expanding at the moment of
diagnosis or initiated exponential growth shortly after. However, in many types
of cancer, patients succumb to metastatic disease years and sometimes decades
after being treated for a primary tumor. This has led to the notion that in these
patients residual disease may remain in a dormant state. Tumor cell dormancy is a
poorly understood phase of cancer progression and only recently have its
underlying molecular mechanisms started to be revealed. Important questions that
remain to be elucidated include not only which mechanisms prevent residual
disease from proliferating but also which mechanisms critically maintain the long
term survival of these disseminated residual cells. Herein, we review recent
evidence in support of genetic and epigenetic mechanisms driving dormancy. We
also explore how therapy may cause the onset of dormancy in the surviving
fraction of cells after treatment and how autophagy may be a mechanism that
maintains the residual cells that are viable for prolonged periods.
PMID- 23143978
TI - Multifaceted kinetics of immuno-evasion from tumor dormancy.
AB - Tumor progression is subject to modulation by the immune system. The immune
system can eliminate tumors or keep them at a dormant equilibrium size, while
some tumors escape immunomodulation and advance to malignancy. Herein, we discuss
some aspects of immune evasion of dormant tumors from a theoretical biophysics
point of view that can be modeled mathematically. We go on to analyze the
mathematical system on multiple timescales. First, we consider a long timescale
where tumor evasion is likely due to adaptive (and somewhat deterministic) immuno
editing. Then, we consider the temporal mesoscale and hypothesize that extrinsic
noise could be a major factor in induction of immuno-evasion. Implications of
immuno-evasive mechanisms for the outcome of immunotherapies are also discussed.
In addition, we discuss the ideas that population level tumor dormancy may not be
a quiescence phenomenon and that dormant tumors can, at least if modulated by the
immune system, live a very active and noisy life!
PMID- 23143979
TI - Tumor dormancy and cancer stem cells: two sides of the same coin?
AB - Increasing evidence suggests that tumor dormancy represents an important
mechanism underlying the observed failure of existing therapeutic modalities to
fully eradicate cancers. In addition to its more established role in maintaining
minimal residual disease after treatment, dormancy might also critically
contribute to early stages of tumor development and the formation of clinically
undetectable micrometastatic foci. There are striking parallels between the
concept of tumor dormancy and the cancer stem cell (CSC) theory of tumor
propagation. For instance, the CSC hypothesis similarly predicts that a subset of
self-renewing cancer cells-that is CSCs-is responsible for tumor initiation,
bears the preferential ability to survive tumor therapy, and persists long term
to ultimately cause delayed cancer recurrence and metastatic progression.
Additionally, many of the biological mechanisms involved in controlling the
dormant state of a tumor can also govern CSC behavior, including cell cycle
modifications, alteration of angiogenic processes, and modulation of antitumor
immune responses. In fact, quiescence and immune escape are emerging hallmark
features of at least some CSCs, indicating significant overlap between dormant
cancer populations and CSCs. Herein, we crucially dissect whether CSCs occupy
specific roles in orchestrating the switch between dormancy and exuberant tumor
growth. We elucidate how recently uncovered CSC biological features could enable
these cells to evade immunologic clearance and regulate cancer expansion,
relapse, and progression. We propose that the study of CSC immunobiological
pathways holds the promise to critically advance our understanding of the
processes mediating tumor dormancy. Ultimately, such research endeavors could
unravel novel therapeutic avenues that efficiently target both proliferating and
dormant CSCs to minimize the risk of tumor recurrence in cancer patients.
PMID- 23143977
TI - Tumor dormancy, oncogene addiction, cellular senescence, and self-renewal
programs.
AB - Cancers are frequently addicted to initiating oncogenes that elicit aberrant
cellular proliferation, self-renewal, and apoptosis. Restoration of oncogenes to
normal physiologic regulation can elicit dramatic reversal of the neoplastic
phenotype, including reduced proliferation and increased apoptosis of tumor cells
(Science 297(5578):63-64, 2002). In some cases, oncogene inactivation is
associated with compete elimination of a tumor. However, in other cases, oncogene
inactivation induces a conversion of tumor cells to a dormant state that is
associated with cellular differentiation and/or loss of the ability to self
replicate. Importantly, this dormant state is reversible, with tumor cells
regaining the ability to self-renew upon oncogene reactivation. Thus,
understanding the mechanism of oncogene inactivation-induced dormancy may be
crucial for predicting therapeutic outcome of targeted therapy. One important
mechanistic insight into tumor dormancy is that oncogene addiction might involve
regulation of a decision between self-renewal and cellular senescence. Recent
evidence suggests that this decision is regulated by multiple mechanisms that
include tumor cell-intrinsic, cell-autonomous mechanisms and host-dependent,
tumor cell-non-autonomous programs (Mol Cell 4(2):199-207, 1999; Science
297(5578):102-104, 2002; Nature 431(7012):1112-1117, 2004; Proc Natl Acad Sci U S
A 104(32):13028-13033, 2007). In particular, the tumor microenvironment, which is
known to be critical during tumor initiation (Cancer Cell 7(5):411-423, 2005; J
Clin Invest 121(6):2436-2446, 2011), prevention (Nature 410(6832):1107-1111,
2001), and progression (Cytokine Growth Factor Rev 21(1):3-10, 2010), also
appears to dictate when oncogene inactivation elicits the permanent loss of self
renewal through induction of cellular senescence (Nat Rev Clin Oncol 8(3):151
160, 2011; Science 313(5795):1960-1964, 2006; N Engl J Med 351(21):2159-21569,
2004). Thus, oncogene addiction may be best modeled as a consequence of the
interplay amongst cell-autonomous and host-dependent programs that define when a
therapy will result in tumor dormancy.
PMID- 23143980
TI - Tumor dormancy: long-term survival in a hostile environment.
AB - Tumor dormancy occurs when cancer cells are present but the tumor does not grow.
Following treatment, patients may enter complete remission in which persistent
cells represent the minimal residual disease (MRD). Experimental models and
clinical data suggest that the absolute quantity of this MRD is extremely low.
Very few cancer cells can persist for years or decades under these hostile
conditions that include continuous exposure to maintenance treatment, autologous
anti-tumor immune response, and a nonpermissive microenvironment. Dormant tumor
cells may survive despite these destruction factors if they adapt and develop
strategies to escape from cell death. Escape may result in a state of equilibrium
between MRD and the patient. Equilibrium between the immune response and tumor
cells can result in long-term tumor dormancy; however, after variable lengths of
time, tumor dormancy ends, and the disease progresses. Experimental models have
shown that dormant tumor cells may over-express B7-H1 and B7.1 and inhibit
cytotoxic T-cell mediated lysis. This resistance could be therapeutically
targeted using drugs like MEK inhibitors that modulate pathways involved in B7-H1
expression. Dormant tumor cells may also develop nonspecific resistance
mechanisms to cell death, such as deregulation of JAK/STAT and mTORC2/AKT
pathways or autocrine and paracrine production of cytokines. This deregulation
leads to cross-resistance between the immune response and cytotoxic drugs,
indicating that the long-term selection that occurs in vivo during tumor dormancy
may ultimately result in resistant relapse. Long-term selection of cancer cells
in vitro using tyrosine kinase inhibitors selects cells that harbor the same
resistance mechanisms as dormant tumor cells. Elucidating the mechanisms
underlying the equilibrium that allows for the persistence of dormant tumor cells
presents a novel strategy for targeted drug treatment in the context of
maintenance therapy.
PMID- 23143981
TI - A review of mathematical models of cancer-immune interactions in the context of
tumor dormancy.
AB - The role of the immune system in tumor dormancy is now well established. In an
immune-induced dormant state, potentially lethal cancer cells persist in a state
where growth is restricted, to little or no increase, by the host's immune
response. To describe this state in the context of cancer progression and immune
response, basic temporal (spatially homogeneous) quantitative predator-prey
constructs are discussed, along with some current and proposed augmentations that
incorporate potentially significant biological phenomena such as the cancer cell
transition to a quiescent state or the time delay in T-cell activation. Advances
in cancer-immune modeling that describe complex interactions underlying the
ability of the immune system to both promote and inhibit tumor growth are
emphasized. Finally, the review concludes by discussing future mathematical
challenges and their biological significance.
PMID- 23143982
TI - Regulation of tumor dormancy and role of microenvironment: a mathematical model.
AB - Herein, a mathematical model of a molecular control system for the regulation of
secondary tumors is formulated and analyzed to explore how secondary tumors can
be controlled by a primary tumor with/without a surgery and the microenvironment.
This control system is composed of fibroblast growth factor-2 (FGF2), urokinase
type plasminogen activator (uPA), plasmin, transforming growth factor-beta
(TGFbeta), latent TGFbeta (LTGFbeta), and tumor density. The control of secondary
tumors by primary tumors was first modeled by Boushaba, Nilsen-Hamiton and Levine
in [46]. The model is based on the idea that the vascularization of a secondary
tumor can be suppressed by inhibitors from a larger primary tumor. The emergence
of tumors at secondary sites 5-7 cm from a primary site was observed after
surgical removal of the primary tumor in silico. The model supports the notion
that the fate of secondary tumors after surgery depends on the distance from the
primary tumor and the surrounding microenvironment. As such, the primary tumor
did not influence the growth of remote secondary tumors, but it could effectively
suppress the growth of the secondary tumors if they were too close to the primary
tumor, even after it was removed. Thus, the model predicts the emergence of
secondary tumors after the excision of the primary tumor when the distance
between these tumors is in the "distance window." It also predicts that the
growth behaviors of the secondary tumors depend on the local microenvironment.
Based on these findings, we propose several treatment options for better clinical
outcomes.
PMID- 23143983
TI - Seeing the invisible: how mathematical models uncover tumor dormancy, reconstruct
the natural history of cancer, and assess the effects of treatment.
AB - The hypothesis of early metastasis was debated for several decades. Dormant
cancer cells and surgery-induced acceleration of metastatic growth were first
observed in clinical studies and animal experiments conducted more than a century
ago; later, these findings were confirmed in numerous modern studies.In this
primarily methodological work, we discuss critically important, yet largely
unobservable, aspects of the natural history of cancer, such as (1) early
metastatic dissemination; (2) dormancy of secondary tumors; (3) treatment-related
interruption of metastatic dormancy, induction of angiogenesis, and acceleration
of the growth of vascular metastases; and (4) the existence of cancer stem cells.
The hypothesis of early metastasis was debated for several decades. Dormant
cancer cells and surgery-induced acceleration of metastatic growth were first
observed in clinical studies and animal experiments conducted more than a century
ago; later, these findings were confirmed in numerous modern studies.We focus on
the unique role played by very general mathematical models of the individual
natural history of cancer that are entirely mechanistic yet, somewhat
paradoxically, essentially free of assumptions about specific nature of the
underlying biological processes. These models make it possible to reconstruct in
considerable detail the individual natural history of cancer and retrospectively
assess the effects of treatment. Thus, the models can be used as a tool for
generation and validation of biomedical hypotheses related to carcinogenesis,
primary tumor growth, its metastatic dissemination, growth of metastases, and the
effects of various treatment modalities. We discuss in detail one such general
model and review the conclusions relevant to the aforementioned aspects of cancer
progression that were drawn from fitting a parametric version of the model to
data on the volumes of bone metastases in one breast cancer patient and 12
prostate cancer patients.
PMID- 23143984
TI - Construction of an all-carbon quaternary stereocenter by the peptide-catalyzed
asymmetric Michael addition of nitromethane to beta-disubstituted alpha,beta
unsaturated aldehydes.
PMID- 23143985
TI - Cumulative exposure to lead and cognition in persons with Parkinson's disease.
AB - Dementia is an important consequence of Parkinson's disease (PD), with few known
modifiable risk factors. Cumulative exposure to lead, at levels experienced in
the community, may exacerbate PD-related neural dysfunction, resulting in
impaired cognition. Among 101 persons with PD ("cases") and, separately, 50
persons without PD ("controls"), we evaluated cumulative lead exposure, gauged by
tibia and patella bone lead concentrations, in relation to cognitive function,
assessed using a telephone battery developed and validated in a separate sample
of PD patients. We also assessed the interaction between lead and case-control
status. After multivariable adjustment, higher tibia bone lead concentration
among PD cases was associated with worse performance on all of the individual
telephone tests. In particular, tibia lead levels corresponded to significantly
worse performance on a telephone analog of the Mini-Mental State Examination and
tests of working memory and attention. Moreover, higher tibia bone lead
concentration was associated with significantly worse global composite score
encompassing all the cognitive tests (P = 0.04). The magnitude of association per
standard deviation increment in tibia bone lead level was equivalent to the
difference in global scores among controls in our study, who were approximately 7
years apart in age. The tibia lead-cognition association was notably stronger
within cases than within controls (P(difference) = 0.06). Patella bone lead
concentration was not consistently associated with performance on the tests.
These data provide evidence suggesting that cumulative exposure to lead may
result in worsened cognition among persons with PD.
PMID- 23143986
TI - Prenatal maternal stress affects motor function in 51/2-year-old children:
project ice storm.
AB - Evidence suggests that prenatal maternal stress (PNMS) has long-term effects on
several outcomes, yet effects on neuromotor function are relatively unknown. We
aimed to determine whether disaster-related PNMS predicts motor functioning in
young children and whether timing of exposure and sex of the child moderate these
effects. Objective and subjective PNMS levels were assessed among pregnant women
exposed to a natural disaster. Their children's bilateral coordination, balance,
and visual motor integration (VMI) were assessed at 51/2 years. Girls performed
better than boys. Objective stress exposure and subjective distress interacted
such that when subjective distress was high, no added effect of objective
hardship was observed; when subjective distress was low, objective hardship
showed a negative effect. In girls, late pregnancy exposure was associated with
poorer outcomes. In conclusion, disaster-related PNMS is associated with
relatively lower motor functions in exposed offspring. Exposure timing, sex, and
type of stress influenced the effects.
PMID- 23143988
TI - Enhancement and modulation of enzymatic activity through higher-order structural
changes of giant DNA-protein multibranch conjugates.
PMID- 23143987
TI - MicroRNA-146a-mediated downregulation of IRAK1 protects mouse and human small
intestine against ischemia/reperfusion injury.
AB - Intestinal ischemia/reperfusion (I/R) injury causes inflammation and tissue
damage and is associated with high morbidity and mortality. Uncontrolled
activation of the innate immune system through toll-like receptors (Tlr) plays a
key role in I/R-mediated tissue damage but the underlying mechanisms have not
been fully resolved. Here, we identify post-transcriptional upregulation of the
essential Tlr signalling molecule interleukin 1 receptor-associated kinase (Irak)
1 as the causative mechanism for post-ischemic immune hyper-responsiveness of
intestinal epithelial cells. Increased Irak1 protein levels enhanced epithelial
ligand responsiveness, chemokine secretion, apoptosis and mucosal barrier
disruption in an experimental intestinal I/R model using wild-type, Irak1(-/-)
and Tlr4(-/-) mice and ischemic human intestinal tissue. Irak1 accumulation
under hypoxic conditions was associated with reduced K48 ubiquitination and
enhanced Senp1-mediated deSUMOylation of Irak1. Importantly, administration of
microRNA (miR)-146a or induction of miR-146a by the phytochemical
diindolylmethane controlled Irak1 upregulation and prevented immune hyper
responsiveness in mouse and human tissue. These findings indicate that Irak1
accumulation triggers I/R-induced epithelial immune hyper-responsiveness and
suggest that the induction of miR-146a offers a promising strategy to prevent I/R
tissue injury.
PMID- 23143989
TI - Heart rate, heart rate variability and behaviour of horses during air transport.
AB - Heart rate (HR), HR variability (HRV) and behaviour score (BS) of nine horses
were evaluated during an eight-hour air transport between The Netherlands and New
York. HR and HRV parameters were calculated every five minutes during the air
transport. Compared with transit (40+/-3), mean HRs were higher during loading
into the jet stall (67+/-21, P<0.001), loading into the aircraft (47+/-6,
P=0.011), taxiing (50+/-8, P=0.001), and during periods of in-flight turbulence
(46+/-7, P=0.017). During the flight, individual horses showed differences in
mean HR (P=0.005) and peak HR (P<0.001). By contrast with HR data, HRV data did
not differ between stages or horses. BS was highest during turbulence (3.2+/
0.4). However, behaviour did not always correspond with HR measurements: the
least responsive horse had the highest HR. Loading into the jet stall caused the
highest increase in HR and was considered the most stressful event. During
transit, HR was generally comparable with resting rates. Previous studies have
shown that loading and transporting by road caused more elevation in HR than
during loading and transporting by air. HRV data were not found to be useful, and
caution is needed when interpreting HRV data. Not every horse exhibited stress
through visible (evasive) behaviour, and HR measurements may provide an
additional tool to assess stress in horses.
PMID- 23143990
TI - Advancing our understanding of the pathophysiology of cardiac disease using in
vivo assessment of heart structure and function in rodent models.
PMID- 23143991
TI - Effect of acute hypoxia on blood flow in vertebral and internal carotid arteries.
AB - Hypoxia changes the regional distribution of cerebral blood flow and stimulates
the ventilatory chemoreflex, thereby reducing CO2 tension. We examined the
effects of both hypoxia and isocapnic hypoxia on acute changes in internal
carotid (ICA) and vertebral artery (VA) blood flow. Ten healthy male subjects
underwent the following two randomly assigned respiratory interventions after a
resting baseline period with room air: (i) hypoxia; and (ii) isocapnic hypoxia
with a controlled gas mixture (12% O2; inspiratory mmHg). In the isocapnic
hypoxia intervention, subjects were instructed to maintain the rate and depth of
breathing to maintain the level of end-tidal partial pressure of CO2 ( ) during
the resting baseline period. The ICA and VA blood flow (velocity * cross
sectional area) were measured using Doppler ultrasonography. The was decreased (
6.3 +/- 0.9%, P < 0.001) during hypoxia by hyperventilation (minute ventilation
+12.9 +/- 2.2%, P < 0.001), while was unchanged during isocapnic hypoxia. The ICA
blood flow was unchanged (P = 0.429), while VA blood flow increased (+10.3 +/-
3.1%, P = 0.010) during hypoxia. In contrast, isocapnic hypoxia increased both
ICA (+14.5 +/- 1.4%, P < 0.001) and VA blood flows (+10.9 +/- 2.4%, P < 0.001).
Thus, hypoxic vasodilatation outweighed hypocapnic vasoconstriction in the VA,
but not in the ICA. These findings suggest that acute hypoxia elicits an increase
in posterior cerebral blood flow, possibly to maintain essential homeostatic
functions of the brainstem.
PMID- 23143992
TI - Immobilization increases interleukin-6, but not tumour necrosis factor-alpha,
release from the leg during exercise in humans.
AB - Data on interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) release
during acute exercise are not conclusive, and information is lacking about the
impact of physical inactivity. Some studies have shown an increase, but others
report no changes in IL-6 and TNF-alpha release during exercise. We have now
studied the temporal relationship of leg IL-6 and TNF-alpha release before and
during isolated two-legged exercise after 14 days of one-leg immobilization (IM)
while the other leg served as the control (CON) leg. Fifteen healthy male
subjects (mean +/- SEM age, 23 +/- 1 years; body mass index, 23.6 +/- 0.7 kg m(
2); and maximal oxygen uptake, 46.8 +/- 1.4 ml kg(-1) min(-1)) performed 45 min
of two-legged dynamic knee-extensor exercise at 19.6 +/- 0.8 W. Arterial and
femoral venous blood samples from the CON and the IM leg were collected every 15
min during exercise, and leg blood flow was measured with Doppler ultrasound. The
arterial plasma IL-6 concentration increased (P < 0.05) with exercise (rest, 1.3
+/- 0.1 pg ml(-1); 15 min, 1.9 +/- 0.2 pg ml(-1); 30 min, 2.4 +/- 0.2 pg ml(-1);
and 45 min, 3.1 +/- 0.3 pg ml(-1)). Interleukin-6 release occurred after 15 min
of exercise, and the release from the IM leg was significantly greater compared
with the CON leg after 45 min (1114 +/- 152 versus 606 +/- 14 pg min(-1),
respectively, P < 0.05). Tumour necrosis factor-alpha release did not differ
between the CON and the IM leg, and arterial concentrations remained unchanged
during exercise (P > 0.05). In conclusion, prior immobilization enhances release
of IL-6 from the leg during exercise at a moderate workload, and the release is
already present in the early phase of exercise. Neither immobilization nor
exercise had an effect on TNF-alpha release in the working legs.
PMID- 23143993
TI - Effects of glutamine supplementation on muscle function and stress responses in a
mouse model of spinal cord injury.
AB - Spinal cord injury (SCI) results in loss of muscle function due to rapid
breakdown of contractile proteins. Glutamine supplementation improves clinical
outcomes, but its effects on muscle function after SCI are unknown. The benefits
of glutamine in non-skeletal muscle tissues involve elevated heat shock protein
(Hsp)70 and Hsp25, but the muscle response may differ because it is the largest
contributor to plasma glutamine. We tested the hypothesis that glutamine
preserves muscle function after SCI and that this is associated with increased
heat shock protein and reduced inflammatory factors, interleukin-6 (IL-6) and
tumour necrosis factor-alpha (TNFalpha). Changes in plantarflexor force,
fatigability and total myofibrillar, Hsp70, Hsp25, IL-6 and TNFalpha muscle
protein levels were measured 7 days after sham or spinal cord transection surgery
in mice receiving daily placebo or glutamine. Compared with placebo, after SCI
glutamine significantly attenuated the reductions in maximal isometric force
(0.22 +/- 0.01 versus 0.31 +/- 0.03 N, respectively) and fatigue resistance (34
+/- 4 versus 59 +/- 4% of initial force, respectively). Glutamine significantly
ameliorated the loss of myofibrillar protein with spinal cord transection. Spinal
cord transection was associated with decreased Hsp70 and Hsp25 with glutamine
only (45 +/- 3 and 44 +/- 5% of placebo, respectively). Glutamine significantly
reduced spinal cord transection-associated increases in IL-6 and TNFalpha
compared with placebo (38 +/- 6 and 37 +/- 8% of placebo, respectively).
Functionally, early reductions in contractile protein, force and fatigue
resistance after SCI were reversed with glutamine. Spinal cord transection
associated reductions in Hsp70, Hsp25, IL-6 and TNFalpha with glutamine versus
placebo suggest lower stress in the muscle, possibly related to a reduced need to
produce glutamine. These findings support glutamine as a therapeutic intervention
to accelerate recovery of muscle function after SCI.
PMID- 23143994
TI - Deficiency in pulmonary surfactant proteins in mice with fatty acid binding
protein 4-Cre-mediated knockout of the tuberous sclerosis complex 1 gene.
AB - Tuberous sclerosis complex 1 (TSC1) forms a heterodimmer with tuberous sclerosis
complex 2, to inhibit signalling by the mammalian target of rapamycin (mTOR)
complex 1 (mTORC1). The mTORC1 stimulates cell growth by promoting anabolic
cellular processes, such as gene transcription and protein translation, in
response to growth factors and nutrient signals. Originally designed to test the
role of TSC1 in adipocyte function, mice in which the gene for TSC1 was
specifically deleted by the fatty acid binding protein 4 (FABP4)-Cre (Fabp4
Tsc1cKO mice) died prematurely within 48 h after birth. The Fabp4-Tsc1cKO mouse
revealed a much smaller phenotype relative to the wild-type littermates. Maternal
administration of rapamycin, a classical mTOR inhibitor, significantly increased
the survival time of Fabp4-Tsc1cKO mice for up to 23 days. Both macroscopic and
microscopic haemorrhages were observed in the lungs of Fabp4-Tsc1cKO mice, while
other tissues showed no significant changes. Levels of surfactant proteins A and
B demonstrated a significant decrease in the Fabp4-Tsc1cKO mice, which was
rescued by maternal injection of rapamycin. Co-localization of FABP4 or TSC1 with
surfactant protein B was also detected in neonatal pulmonary tissues. Our study
suggests that TSC1-mTORC1 may be critical for the synthesis of surfactant
proteins A and B.
PMID- 23143996
TI - Molybdenum boride and carbide catalyze hydrogen evolution in both acidic and
basic solutions.
PMID- 23143995
TI - Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and
survival.
AB - In amyotrophic lateral sclerosis (ALS) mice, regulatory T-lymphocytes (Tregs) are
neuroprotective, slowing disease progression. To address whether Tregs and FoxP3,
a transcription factor required for Treg function, similarly influence
progression rates of ALS patients, T-lymphocytes from patients were assessed by
flow cytometry. Both numbers of Tregs and their FoxP3 protein expressions were
reduced in rapidly progressing ALS patients and inversely correlated with
progression rates. The mRNA levels of FoxP3, TGF-beta, IL4 and Gata3, a Th2
transcription factor, were reduced in rapidly progressing patients and inversely
correlated with progression rates. Both FoxP3 and Gata3 were accurate indicators
of progression rates. No differences in IL10, Tbx21, a Th1 transcription factor
or IFN-gamma expression were found between slow and rapidly progressing patients.
A 3.5-year prospective study with a second larger cohort revealed that early
reduced FoxP3 levels were indicative of progression rates at collection and
predictive of future rapid progression and attenuated survival. Collectively,
these data suggest that Tregs and Th2 lymphocytes influence disease progression
rates. Importantly, early reduced FoxP3 levels could be used to identify rapidly
progressing patients.
PMID- 23143997
TI - What's wrong with enhancements?
PMID- 23143998
TI - Commentary on Singh: Not robots: children's perspectives on authenticity, moral
agency and stimulant drug treatments.
PMID- 23143999
TI - Experimental reappraisal of continuous dopaminergic stimulation against L-dopa
induced dyskinesia.
PMID- 23144000
TI - Tribenzotriquinacene: a versatile synthesis and C3-chiral platforms.
PMID- 23144001
TI - Real-time fluorescence turn-on detection of alkaline phosphatase activity with a
novel perylene probe.
AB - A tetracationic perylene probe (probe 1) was designed and synthesized. Probe 1
was used for the real-time fluorescence turn-on assay of alkaline phosphatase
(ALP) activity and inhibitor screening. Probe 1 monomer fluorescence could be
very efficiently quenched by ATP through the formation of an ATP/probe 1 complex.
ALP triggered the degradation of ATP, the breakdown of the ATP/probe 1 complex,
and the recovery of the probe 1 monomer fluorescence. In the presence of an ALP
inhibitor, a decrease in fluorescence recovery was observed.
PMID- 23144002
TI - Parkinson's disease patients show reduced cortical-subcortical sensorimotor
connectivity.
AB - Reduced dopamine input to cortical and subcortical brain structures, particularly
those in the sensorimotor network, is a hallmark of Parkinson's disease (PD). The
extent to which dopamine dysfunction affects connectivity within this and other
brain networks remains to be investigated. The purpose of this study was to
measure anatomical and functional connectivity in groups of PD patients and
controls to determine whether connectivity deficits within the cortico-basal
ganglia thalamocortical system could be attributed to PD, particularly in
sensorimotor connections. A neuroimaging paradigm involving diffusion-weighted
magnetic resonance imaging (MRI) and resting-state functional MRI was implemented
in a large cohort of PD patients and control subjects. Probabilistic tractography
and functional correlation analyses were performed to map connections between
brain structures and to derive indices of connectivity that were then used to
compare groups. Anatomical connectivity deficits were demonstrated in PD
patients, specifically for sensorimotor connections. Functional deficits were
also found in some of the same connections. In addition, functional connectivity
was found to increase in associative and limbic connections in PD patients
compared with controls. This study lends support to findings regarding the
dysfunction of the sensorimotor circuit in PD. As deficits in anatomical and
functional connectivity within this circuit were in some cases concordant in PD
patients, a possible link between brain structure and function is suggested.
Increases in functional connectivity in other cortico-basal ganglia
thalamocortical circuits may be indicative of compensatory effects in response to
system deficits elsewhere.
PMID- 23144003
TI - Low pathogenic avian influenza H7N7 in domestic poultry in Germany in 2011.
PMID- 23144004
TI - Enhancing the photocatalytic activity of anatase TiO2 by improving the specific
facet-induced spontaneous separation of photogenerated electrons and holes.
AB - Recently, it has been proven that directional flow of photogenerated charge
carriers occurs on specific facets of TiO(2) nanocrystals. Herein, we
demonstrate that the photocatalytic activity of anatase TiO(2) nanocrystals in
both photoreduction and photooxidation processes can be enhanced by selectively
depositing Pt nanoparticles on the {101} facets, which strengthens spontaneously
surface-induced separation between photogenerated electrons and holes in the
photocatalysis process. An optimal ratio of the oxidative {001} facets to the
reductive {101} facets exists with regard to the photocatalysis of the faceted
TiO(2) nanocrystals, and this is crucial for balancing the recombination and
redox reaction rates of photogenerated electrons and holes. The present work
might help us gain deeper insight into the relation between the specific surface
of semiconductor photocatalysts and their photocatalytic activities and provides
us with a new route to design photocatalysts with high photocatalytic activity.
PMID- 23144005
TI - Quantifying analytes in paper-based microfluidic devices without using external
electronic readers.
PMID- 23144006
TI - 1-Hz repetitive transcranial magnetic stimulation and diphasic dyskinesia in
Parkinson's disease.
PMID- 23144007
TI - A novel approach to standardised recording of bleeding in a high risk neonatal
population.
AB - BACKGROUND: Bleeding assessment tools have been developed in other specialties to
standardise the recording of bleeding for clinical haemostatic outcomes in
transfusion trials, but such tools have not been developed for routine use in
neonatology. AIM: The objective of this study was to develop, refine and evaluate
a neonatal bleeding assessment tool (NeoBAT) to standardise the clinical
recording of bleeding in premature and term neonates in an intensive care
setting. METHODS: This prospective neonatal international multicentre study
included all episodes of bleeding in infants admitted to the intensive/high
dependency care nursery over a 2-4-week period. The NeoBAT was developed to
record neonatal bleeding episodes. We tested its reliability and reproducibility
with duplicate assessments. RESULTS: Duplicate assessments revealed 98%
concordance. Bleeding occurred in 25% (37/146) of infants overall and was most
common in preterm infants. 11% (16/146) infants had major/severe bleeds, 1%
(2/146) moderate and 13% (19/146) minor bleeds. CONCLUSIONS: Bleeding is common
in premature and term neonates admitted to intensive/high dependency care
nurseries. This novel bleeding assessment tool facilitates prospective recording
of bleeding events in neonatal intensive care settings and may allow standardised
bleeding assessments in this high risk population.
PMID- 23144008
TI - Benchmarking in neonatal intensive care: obstetrical and neonatal practices and
registration policies may influence outcome data.
PMID- 23144009
TI - Low-dose aspirin is associated with an increased risk of haemorrhage; but not in
people with diabetes who have a high baseline rate of bleeding.
AB - Implications for practice and research: Low-dose aspirin (<= 300 mg/day)
increases the risk of major bleeding. Individuals with diabetes have a higher
risk of bleeding independent of aspirin exposure. Future work should include
comparative effectiveness studies to help inform treatment strategies based on
individual risks, benefits, patient preferences and values.
PMID- 23144010
TI - Higher nurse staffing levels associated with reductions in unplanned readmissions
to intensive care or operating theatre, and in postoperative in-hospital
mortality in heart surgery patients.
AB - Implications for practice and research: Higher nurse staffing levels for
postoperative care of cardiac surgery patients reduces the risk of unplanned re
admission to the intensive care or operating theatre and in-hospital mortality.
Larger international studies are needed to assess the effect of nurse staffing
levels and risk of hospital-wide adverse events.
PMID- 23144011
TI - A depression screening tool finds that 54% of acute cardiac patients are at risk
of depression; use of the tool improves documentation and referral.
AB - Implications for practice and research: This study found that nurses on
cardiovascular care units were able to administer depression screening tools and
document referral activities for positive screens. It is not known whether
depression screening improved depression outcomes. Evidence of benefits in excess
of harms, established by well-conducted randomised controlled trials (RCTs) of
depression screening interventions, is needed before depression screening is
implemented in cardiovascular care settings.
PMID- 23144012
TI - Asking next-of-kin of recently deceased cancer patients to take part in research:
11 of 20 surveyed found it a positive experience.
AB - Implications for practice and research: These results will aid the development of
protocols for screening bereaved individuals who are eligible for study
participation. These results provide insight into bereaved participants'
preferences for data collection methods (e.g., face-to-face, phone and self
completion postal surveys). The needs of non-cancer-related deaths and paediatric
populations (e.g., bereaved child participants; childhood deaths) need
consideration in future studies.
PMID- 23144013
TI - Mono-PEGylated zinc(II) phthalocyanines: preparation, nanoparticle formation, and
in vitro photodynamic activity.
PMID- 23144014
TI - Elective ventilation and the politics of death.
AB - This essay comments on the British Medical Association's recent suggestion that
protocols for Elective Ventilation (EV) might be revived in order to increase the
number of viable organs available for transplant. I suggest that the proposed
revival results, at least in part, from developments in the contemporary
political landscape, notably the decreasing likelihood of an opt-out system for
the UK's Organ Donor Register. I go on to suggest that EV is unavoidably situated
within complex debates surrounding the epistemology and ontology of death. Such
questions cannot be settled a priori by medical science, bioethics or
philosophical reflection. As Radcliffe-Richards suggests, the determination of
death has become a moral question, and therefore, now extends into the political
arena. I argue for the conclusion that EV, and wider debates about organ donation
and the constitution of the organ donation register, are matters of
'biocitizenship' and must, therefore, be addressed as 'biopolitical' questions.
PMID- 23144015
TI - Translation and cross-cultural adaptation of a family booklet on comfort care in
dementia: sensitive topics revised before implementation.
AB - INTRODUCTION: Families of patients with dementia may need support in difficult
end-of-life decision making. Such guidance may be culturally sensitive. METHODS:
To support families in Canada, a booklet was developed to aid decision making on
palliative care issues. For reasons of cost effectiveness and promising effects,
we prepared for its implementation in Italy, the Netherlands and Japan. Local
teams translated and adapted the booklet to local ethical, legal and medical
standards where needed, retaining guidance on palliative care. Using qualitative
content analyses, we grouped and compared adaptations to understand culturally
sensitive aspects. RESULTS: Three themes emerged: (1) relationships among
patient, physician and other professionals-the authority of the physician was
more explicit in adapted versions; (2) patient rights and family position-adding
detail about local regulations; and (3) typology of treatments and decisions.
Considerations underlying palliative care decisions were detailed (Dutch and
Italian versions), and the Japanese version frequently referred to professional
and legal standards, and life-prolongation was a competing goal. Text on
artificial feeding or fluids and euthanasia was revised extensively. CONCLUSIONS:
Providing artificial feeding and fluids and discussing euthanasia may be
particularly sensitive topics, and guidance on these subjects needs careful
consideration of ethical aspects and possible adaptations to local standards and
practice. The findings may promote cross-national debate on sensitive, core
issues regarding end-of-life care in dementia.
PMID- 23144016
TI - Fastest thermal isomerization of an azobenzene for nanosecond photoswitching
applications under physiological conditions.
PMID- 23144019
TI - Chronic abdominal pain in children: help in spotting the organic diagnosis.
PMID- 23144020
TI - Preferential formation of cyclic trimers by palladium-catalyzed oxidative
coupling reactions of 2,18-diethynylporphyrins.
PMID- 23144021
TI - Hypoxia and PGE(2) regulate MiTF-CX during cervical ripening.
AB - The mechanisms by which the cervix remains closed during the massive uterine
expansion of pregnancy are unknown. IL-8 is important for recruitment of immune
cells into the cervical stroma, matrix remodeling, and dilation of the cervix
during labor. Previously, we have shown that several cytokine genes
transcriptionally repressed in the cervix during gestation are activated during
cervical ripening and dilation. IL-8 gene expression is repressed in cervical
stromal cells during pregnancy by the transcription factor microphthalmia
associated transcription factor (MiTF-CX). Here, we tested the hypothesis that
hypoxia and the transcription factor hypoxia inducible factor-1alpha (HIF-1alpha)
may regulate MiTF-CX and cervical ripening. Using tissues from women during
pregnancy before and after cervical ripening, we show that, during cervical
ripening, HIF-1alpha was stabilized and relocalized to the nucleus. Further, we
found that hypoxia and two hypoxia mimetics that stabilize HIF-1alpha activated
the transcriptional repressor differentiated embryo chondrocyte-expressed gene 1,
which bound to sites in the MiTF-CX promoter crucial for its positive
autoregulation. Ectopic overexpression of MiTF-CX abrogated hypoxia-induced up
regulation of IL-8 gene expression. We also show that activation of HIF-1alpha
induced cyclooxygenase-2 and that prostaglandin E(2) repressed MiTF-CX. We
conclude that hypoxia and stabilization of the transcription factor HIF-1alpha
result in up-regulation of differentiated embryo chondrocyte-expressed gene 1,
loss of MiTF, and absence of MiTF binding to the IL-8 promoter, which in turn
leads to up-regulation of IL-8 gene expression. Hypoxia also up-regulated
cyclooxygenase-2, leading to prostaglandin E(2)-mediated loss of MiTF in cervical
stromal cells. The results support a pivotal role for hypoxia and HIF-1alpha in
the cervical ripening process during pregnancy.
PMID- 23144022
TI - He's a real man: a qualitative study of the social context of couples' vasectomy
decisions among a racially diverse population.
AB - Vasectomy has advantages with respect to safety and cost when compared with
female sterilization. The reasons underlying the overall low use of vasectomy,
particularly among Black and Latinos, have not been adequately explored. The
goals of this study were to (a) explore the social context of vasectomy decisions
and (b) generate hypotheses about the social factors contributing to differences
in vasectomy use by race/ethnicity. Fourteen group and nine couples interviews
were conducted. Participants were 37 heterosexual couples aged 25 to 55 years who
had reached their desired family size and self-identified as Black, Latino, or
White. Participants discussed reasons that men and women would or would not
select male sterilization. Reasons to select vasectomy included a desire to care
for their current family, sharing contraceptive responsibility, and infidelity.
Reasons not to select vasectomy included negative associations with the term
sterilization, loss of manhood, and permanence. Misconceptions about vasectomy
included misunderstandings about the vasectomy procedure and adverse
postvasectomy sexual function. In addition, Black and Latino participants cited
perceived ease of reversibility of female sterilization and lack of support
around vasectomy as reasons not to choose it. Improving communication and social
support for vasectomy, particularly among Black and Latino communities, may
improve vasectomy utilization. Misconceptions regarding female and male
sterilization should be targeted in counseling sessions to ensure men, women, and
couples are making informed contraceptive decisions.
PMID- 23144023
TI - Tissue classification using ultrasound-induced variations in acoustic
backscattering features.
AB - Ultrasound (US) radio-frequency (RF) time series is an effective tissue
classification method that enables accurate cancer diagnosis, but the mechanisms
underlying this method are not completely understood. This paper presents a model
to describe the variations in tissue temperature and sound speed that take place
during the RF time series scanning procedures and relate these variations to US
backscattering. The model was used to derive four novel characterization
features. These features were used to classify three animal tissues, and they
obtained accuracies as high as 88.01%. The performance of the proposed features
was compared with RF time series features proposed in a previous study. The
results indicated that the US-induced variations in tissue temperature and sound
speed, which were used to derive the proposed features, were important
contributors to the tissue typing capabilities of the RF time series. Simulations
carried out to estimate the heating induced during the scanning procedure
employed in this study showed temperature rises lower than 2 degrees C. The
model and results presented in this paper can be used to improve the RF time
series.
PMID- 23144024
TI - Elastic light single-scattering spectroscopy for the detection of cervical
precancerous ex vivo.
AB - Potential application of elastic light single-scattering spectroscopy (ELSSS) for
differentiating high-grade squamous intraepithelial lesions (HSIL) from non-HSIL
tissues was investigated. An ELSSS system was used to acquire spectra from cervix
tissues. A single-fiber optical probe with a diameter of 100 MUm was used for
both delivery and detection of white light to and from the cervix tissue.
Spectroscopic measurements were acquired from 95 ex vivo biopsy samples of 60 pap
smear positive patients and normal cervix tissue from 10 patients after
hysterectomy were used as a negative control group. Spectroscopic results of 95
cervix biopsy were compared to the histopathology of the biopsy samples.
Sensitivity and specificity of the ELSSS system in the differentiation of HSIL
and non-HSIL tissues are 87.5% and 45.6%, respectively, for the pap smear and
colposcopy positive biopsy samples. The ELSSS system has the potential for use in
real-time diagnosis of HSIL tissues as an adjunct to Papanicolaou test (pap
smear) and colposcopy.
PMID- 23144025
TI - Introducing Willmore flow into level set segmentation of spinal vertebrae.
AB - Segmentation of spinal vertebrae in 3-D space is a crucial step in the study of
spinal related disease or disorders. However, the complexity of vertebrae shapes,
with gaps in the cortical bone and boundaries, as well as noise, inhomogeneity,
and incomplete information in images, has made spinal vertebrae segmentation a
difficult task. In this paper, we introduce a new method for an accurate spinal
vertebrae segmentation that is capable of dealing with noisy images with missing
information. This is achieved by introducing an edge-mounted Willmore flow, as
well as a prior shape kernel density estimator, to the level set segmentation
framework. While the prior shape model provides much needed prior knowledge when
information is missing from the image, and draws the level set function toward
prior shapes, the edge-mounted Willmore flow helps to capture the local geometry
and smoothes the evolving level set surface. Evaluation of the segmentation
results with ground-truth validation demonstrates the effectiveness of the
proposed approach: an overall accuracy of 89.32+/-1.70% and 14.03+/-1.40 mm are
achieved based on the Dice similarity coefficient and Hausdorff distance,
respectively, while the inter- and intraobserver variation agreements are
92.11+/-1.97%, 94.94+/-1.69%, 3.32+/-0.46, and 3.80+/-0.56 mm.
PMID- 23144026
TI - Robust alignment of prostate histology slices with quantified accuracy.
AB - No current imaging technique is capable of detecting with precision tumors in the
prostate. To evaluate each technique, the histology data must be precisely mapped
to the imaged data. As the histology slices cannot be assumed to be cut along the
same plane as the imaged data were acquired, the registration must be considered
as a 3-D problem. This requires the prior alignment of the histology slices. We
propose a protocol in which three needles are inserted into the fresh prostate,
creating internal fiducial markers visible in the histology slices. Our algorithm
then automatically detects and identifies these markers, enabling the automatic
rigid alignment of each slice. The accuracy of the algorithm was quantified in
simulated images, a beef liver sample in which a validation marker had been
created, and ten prostate specimens. The simulated images showed that the
algorithm has no associated residual error for a situation where there is no
deformation. In the beef liver images, the average accuracy of the alignment was
0.12 +/- 0.09 mm at the fiducial markers, and 0.62 +/- 0.46 mm at a validation
marker positioned approximately 20 mm from the fiducial markers. Concerning the
ten prostates, there were 19.2 histology slices on average per specimen. On
average, 93.7% of the fiducial markers created were visible in the slices, of
which 96.1% were then automatically and correctly detected and identified,
enabling an alignment of average accuracy 0.18 +/- 0.13 mm at the fiducial
markers. As a cancer of volume <0.5 cm(3) is classified as clinically
insignificant, the accuracy achieved justified the choice of a rigid
registration. An attractive feature of this method is the time required, less
than 6 min on average per prostate specimen.
PMID- 23144027
TI - Design and performance evaluation of a minimally invasive telerobotic platform
for transurethral surveillance and intervention.
AB - Bladder cancer, a significant cause of morbidity and mortality worldwide,
presents a unique opportunity for aggressive treatment due to the ease of
transurethral accessibility. While the location affords advantages, transurethral
resection of bladder tumors can pose a difficult challenge for surgeons
encumbered by current instrumentation or difficult anatomic tumor locations. This
paper presents the design and evaluation of a telerobotic system for
transurethral surveillance and surgical intervention. The implementation seeks to
improve current procedures and enable development of new surgical techniques by
providing a platform for intravesicular dexterity and integration of novel
imaging and interventional instrumentation. The system includes a dexterous
continuum robot with access channels for the parallel deployment of multiple
visualization and surgical instruments. This paper first presents the clinical
conditions imposed by transurethral access and the limitations of the current
state-of-the-art instrumentation. Motivated by the clinical requirements, the
design considerations for this system are discussed and the prototype system is
presented. Telemanipulation evaluation demonstrates submillimetric RMS
positioning accuracy and intravesicular dexterity suitable for improving
transurethral surveillance and intervention.
PMID- 23144028
TI - Compressed sensing for energy-efficient wireless telemonitoring of noninvasive
fetal ECG via block sparse Bayesian learning.
AB - Fetal ECG (FECG) telemonitoring is an important branch in telemedicine. The
design of a telemonitoring system via a wireless body area network with low
energy consumption for ambulatory use is highly desirable. As an emerging
technique, compressed sensing (CS) shows great promise in
compressing/reconstructing data with low energy consumption. However, due to some
specific characteristics of raw FECG recordings such as nonsparsity and strong
noise contamination, current CS algorithms generally fail in this application.
This paper proposes to use the block sparse Bayesian learning framework to
compress/reconstruct nonsparse raw FECG recordings. Experimental results show
that the framework can reconstruct the raw recordings with high quality.
Especially, the reconstruction does not destroy the interdependence relation
among the multichannel recordings. This ensures that the independent component
analysis decomposition of the reconstructed recordings has high fidelity.
Furthermore, the framework allows the use of a sparse binary sensing matrix with
much fewer nonzero entries to compress recordings. Particularly, each column of
the matrix can contain only two nonzero entries. This shows that the framework,
compared to other algorithms such as current CS algorithms and wavelet
algorithms, can greatly reduce code execution in CPU in the data compression
stage.
PMID- 23144029
TI - The transesophageal echocardiography simulator based on computed tomography
images.
AB - Simulators are a new tool in education in many fields, including medicine, where
they greatly improve familiarity with medical procedures, reduce costs, and,
importantly, cause no harm to patients. This is so in the case of transesophageal
echocardiography (TEE), in which the use of a simulator facilitates spatial
orientation and helps in case studies. The aim of the project described in this
paper is to simulate an examination by TEE. This research makes use of available
computed tomography data to simulate the corresponding echocardiographic view.
This paper describes the essential characteristics that distinguish these two
modalities and the key principles of the wave phenomena that should be considered
in the simulation process, taking into account the conditions specific to the
echocardiography. The construction of the CT2TEE (Web-based TEE simulator) is
also presented. The considerations include ray-tracing and ray-casting techniques
in the context of ultrasound beam and artifact simulation. An important aspect of
the interaction with the user is raised.
PMID- 23144030
TI - A robust ultrashort TE (UTE) imaging method with corrected k-space trajectory by
using parametric multiple function model of gradient waveform.
AB - Ultra-short TE (UTE) sequences with radial sampling make it possible to visualize
tissues with very short T2 decay times. The UTE sequence acquires an echo signal
from the central to the outer parts of k-space and is very sensitive to small
trajectory errors. Therefore, k-space errors caused by imperfections in the
gradient system performance, such as gradient delay and waveform distortion, must
be corrected. During normal clinical use, these errors must be corrected to
account for any gradient strength, or image obliquity. Because of time limitation
on clinical examination, a simple, robust, and time-efficient correction method
for use with UTE is needed. We demonstrated image degradation due to k-space
errors by simulation and found that uncontrolled gradient time delays were the
dominant cause of image degradation. They could be corrected by using a pre-scan
calibration that works by comparison of half and full echo signals. Further
improvements in image quality were achieved by using a one-time calibration of
gradient waveform approximations that were built from multiple exponential
functions and were used during image reconstruction. We have developed a robust
UTE correction method that consists of a gradient waveform approximation that
follows a short pre-scan for estimating gradient time delay errors.
PMID- 23144031
TI - Flip-invariant SIFT for copy and object detection.
AB - Scale-invariant feature transform (SIFT) feature has been widely accepted as an
effective local keypoint descriptor for its invariance to rotation, scale, and
lighting changes in images. However, it is also well known that SIFT, which is
derived from directionally sensitive gradient fields, is not flip invariant. In
real-world applications, flip or flip-like transformations are commonly observed
in images due to artificial flipping, opposite capturing viewpoint, or symmetric
patterns of objects. This paper proposes a new descriptor, named flip-invariant
SIFT (or F-SIFT), that preserves the original properties of SIFT while being
tolerant to flips. F-SIFT starts by estimating the dominant curl of a local patch
and then geometrically normalizes the patch by flipping before the computation of
SIFT. We demonstrate the power of F-SIFT on three tasks: large-scale video copy
detection, object recognition, and detection. In copy detection, a framework,
which smartly indices the flip properties of F-SIFT for rapid filtering and weak
geometric checking, is proposed. F-SIFT not only significantly improves the
detection accuracy of SIFT, but also leads to a more than 50% savings in
computational cost. In object recognition, we demonstrate the superiority of F
SIFT in dealing with flip transformation by comparing it to seven other
descriptors. In object detection, we further show the ability of F-SIFT in
describing symmetric objects. Consistent improvement across different kinds of
keypoint detectors is observed for F-SIFT over the original SIFT.
PMID- 23144032
TI - Shape sparse representation for joint object classification and segmentation.
AB - In this paper, a novel variational model based on prior shapes for simultaneous
object classification and segmentation is proposed. Given a set of training
shapes of multiple object classes, a sparse linear combination of training shapes
in a low-dimensional representation is used to regularize the target shape in
variational image segmentation. By minimizing the proposed variational
functional, the model is able to automatically select the reference shapes that
best represent the object by sparse recovery and accurately segment the image,
taking into account both the image information and the shape priors. For some
applications under an appropriate size of training set, the proposed model allows
artificial enlargement of the training set by including a certain number of
transformed shapes for transformation invariance, and then the model remains
jointly convex and can handle the case of overlapping or multiple objects
presented in an image within a small range. Numerical experiments show promising
results and the potential of the method for object classification and
segmentation.
PMID- 23144033
TI - Multiscale image fusion using the undecimated wavelet transform with spectral
factorization and nonorthogonal filter banks.
AB - Multiscale transforms are among the most popular techniques in the field of pixel
level image fusion. However, the fusion performance of these methods often
deteriorates for images derived from different sensor modalities. In this paper,
we demonstrate that for such images, results can be improved using a novel
undecimated wavelet transform (UWT)-based fusion scheme, which splits the image
decomposition process into two successive filtering operations using spectral
factorization of the analysis filters. The actual fusion takes place after
convolution with the first filter pair. Its significantly smaller support size
leads to the minimization of the unwanted spreading of coefficient values around
overlapping image singularities. This usually complicates the feature selection
process and may lead to the introduction of reconstruction errors in the fused
image. Moreover, we will show that the nonsubsampled nature of the UWT allows the
design of nonorthogonal filter banks, which are more robust to artifacts
introduced during fusion, additionally improving the obtained results. The
combination of these techniques leads to a fusion framework, which provides clear
advantages over traditional multiscale fusion approaches, independent of the
underlying fusion rule, and reduces unwanted side effects such as ringing
artifacts in the fused reconstruction.
PMID- 23144034
TI - Context-dependent logo matching and recognition.
AB - We contribute, through this paper, to the design of a novel variational framework
able to match and recognize multiple instances of multiple reference logos in
image archives. Reference logos and test images are seen as constellations of
local features (interest points, regions, etc.) and matched by minimizing an
energy function mixing: 1) a fidelity term that measures the quality of feature
matching, 2) a neighborhood criterion that captures feature co
occurrence/geometry, and 3) a regularization term that controls the smoothness of
the matching solution. We also introduce a detection/recognition procedure and
study its theoretical consistency. Finally, we show the validity of our method
through extensive experiments on the challenging MICC-Logos dataset. Our method
overtakes, by 20%, baseline as well as state-of-the-art matching/recognition
procedures.
PMID- 23144035
TI - Efficient contrast enhancement using adaptive gamma correction with weighting
distribution.
AB - This paper proposes an efficient method to modify histograms and enhance contrast
in digital images. Enhancement plays a significant role in digital image
processing, computer vision, and pattern recognition. We present an automatic
transformation technique that improves the brightness of dimmed images via the
gamma correction and probability distribution of luminance pixels. To enhance
video, the proposed image-enhancement method uses temporal information regarding
the differences between each frame to reduce computational complexity.
Experimental results demonstrate that the proposed method produces enhanced
images of comparable or higher quality than those produced using previous state
of-the-art methods.
PMID- 23144036
TI - Comments on "A robust fuzzy local information C-means clustering algorithm".
AB - In a recent paper, Krinidis and Chatzis proposed a variation of fuzzy c-means
algorithm for image clustering. The local spatial and gray-level information are
incorporated in a fuzzy way through an energy function. The local minimizers of
the designed energy function to obtain the fuzzy membership of each pixel and
cluster centers are proposed. In this paper, it is shown that the local
minimizers of Krinidis and Chatzis to obtain the fuzzy membership and the cluster
centers in an iterative manner are not exclusively solutions for true local
minimizers of their designed energy function. Thus, the local minimizers of
Krinidis and Chatzis do not converge to the correct local minima of the designed
energy function not because of tackling to the local minima, but because of the
design of energy function.
PMID- 23144037
TI - Exponential local discriminant embedding and its application to face recognition.
AB - Local discriminant embedding (LDE) has been recently proposed to overcome some
limitations of the global linear discriminant analysis method. In the case of a
small training data set, however, LDE cannot directly be applied to high
dimensional data. This case is the so-called small-sample-size (SSS) problem. The
classical solution to this problem was applying dimensionality reduction on the
raw data (e.g., using principal component analysis). In this paper, we introduce
a novel discriminant technique called "exponential LDE" (ELDE). The proposed ELDE
can be seen as an extension of LDE framework in two directions. First, the
proposed framework overcomes the SSS problem without discarding the discriminant
information that was contained in the null space of the locality preserving
scatter matrices associated with LDE. Second, the proposed ELDE is equivalent to
transforming original data into a new space by distance diffusion mapping
(similar to kernel-based nonlinear mapping), and then, LDE is applied in such a
new space. As a result of diffusion mapping, the margin between samples belonging
to different classes is enlarged, which is helpful in improving classification
accuracy. The experiments are conducted on five public face databases: Yale,
Extended Yale, PF01, Pose, Illumination, and Expression (PIE), and Facial
Recognition Technology (FERET). The results show that the performances of the
proposed ELDE are better than those of LDE and many state-of-the-art discriminant
analysis techniques.
PMID- 23144038
TI - Optimal Selection of Parameters for Nonuniform Embedding of Chaotic Time Series
Using Ant Colony Optimization.
AB - The optimal selection of parameters for time-delay embedding is crucial to the
analysis and the forecasting of chaotic time series. Although various parameter
selection techniques have been developed for conventional uniform embedding
methods, the study of parameter selection for nonuniform embedding is progressed
at a slow pace. In nonuniform embedding, which enables different dimensions to
have different time delays, the selection of time delays for different dimensions
presents a difficult optimization problem with combinatorial explosion. To solve
this problem efficiently, this paper proposes an ant colony optimization (ACO)
approach. Taking advantage of the characteristic of incremental solution
construction of the ACO, the proposed ACO for nonuniform embedding (ACO-NE)
divides the solution construction procedure into two phases, i.e., selection of
embedding dimension and selection of time delays. In this way, both the embedding
dimension and the time delays can be optimized, along with the search process of
the algorithm. To accelerate search speed, we extract useful information from the
original time series to define heuristics to guide the search direction of ants.
Three geometry- or model-based criteria are used to test the performance of the
algorithm. The optimal embeddings found by the algorithm are also applied in time
series forecasting. Experimental results show that the ACO-NE is able to yield
good embedding solutions from both the viewpoints of optimization performance and
prediction accuracy.
PMID- 23144039
TI - Efficient shortest-path-tree computation in network routing based on pulse
coupled neural networks.
AB - Shortest path tree (SPT) computation is a critical issue for routers using link
state routing protocols, such as the most commonly used open shortest path first
and intermediate system to intermediate system. Each router needs to recompute a
new SPT rooted from itself whenever a change happens in the link state. Most
commercial routers do this computation by deleting the current SPT and building a
new one using static algorithms such as the Dijkstra algorithm at the beginning.
Such recomputation of an entire SPT is inefficient, which may consume a
considerable amount of CPU time and result in a time delay in the network. Some
dynamic updating methods using the information in the updated SPT have been
proposed in recent years. However, there are still many limitations in those
dynamic algorithms. In this paper, a new modified model of pulse-coupled neural
networks (M-PCNNs) is proposed for the SPT computation. It is rigorously proved
that the proposed model is capable of solving some optimization problems, such as
the SPT. A static algorithm is proposed based on the M-PCNNs to compute the SPT
efficiently for large-scale problems. In addition, a dynamic algorithm that makes
use of the structure of the previously computed SPT is proposed, which
significantly improves the efficiency of the algorithm. Simulation results
demonstrate the effective and efficient performance of the proposed approach.
PMID- 23144040
TI - Class of multiple sequence alignment algorithm affects genomic analysis.
AB - Multiple sequence alignment (MSA) is the heart of comparative sequence analysis.
Recent studies demonstrate that MSA algorithms can produce different outcomes
when analyzing genomes, including phylogenetic tree inference and the detection
of adaptive evolution. These studies also suggest that the difference between MSA
algorithms is of a similar order to the uncertainty within an algorithm and
suggest integrating across this uncertainty. In this study, we examine further
the problem of disagreements between MSA algorithms and how they affect
downstream analyses. We also investigate whether integrating across alignment
uncertainty affects downstream analyses. We address these questions by analyzing
200 chordate gene families, with properties reflecting those used in large-scale
genomic analyses. We find that newly developed distance metrics reveal two
significantly different classes of MSA methods (MSAMs). The similarity-based
class includes progressive aligners and consistency aligners, representing many
methodological innovations for sequence alignment, whereas the evolution-based
class includes phylogenetically aware alignment and statistical alignment. We
proceed to show that the class of an MSAM has a substantial impact on downstream
analyses. For phylogenetic inference, tree estimates and their branch lengths
appear highly dependent on the class of aligner used. The number of families, and
the sites within those families, inferred to have undergone adaptive evolution
depend on the class of aligner used. Similarity-based aligners tend to identify
more adaptive evolution. We also develop and test methods for incorporating MSA
uncertainty when detecting adaptive evolution but find that although accounting
for MSA uncertainty does affect downstream analyses, it appears less important
than the class of aligner chosen. Our results demonstrate the critical role that
MSA methodology has on downstream analysis, highlighting that the class of
aligner chosen in an analysis has a demonstrable effect on its outcome.
PMID- 23144041
TI - Iris-based medical analysis by geometric deformation features.
AB - Iris analysis studies the relationship between human health and changes in the
anatomy of the iris. Apart from the fact that iris recognition focuses on
modeling the overall structure of the iris, iris diagnosis emphasizes the
detecting and analyzing of local variations in the characteristics of irises.
This paper focuses on studying the geometrical structure changes in irises that
are caused by gastrointestinal diseases, and on measuring the observable
deformations in the geometrical structures of irises that are related to
roundness, diameter and other geometric forms of the pupil and the collarette.
Pupil and collarette based features are defined and extracted. A series of
experiments are implemented on our experimental pathological iris database,
including manual clustering of both normal and pathological iris images, manual
classification by non-specialists, manual classification by individuals with a
medical background, classification ability verification for the proposed
features, and disease recognition by applying the proposed features. The results
prove the effectiveness and clinical diagnostic significance of the proposed
features and a reliable recognition performance for automatic disease diagnosis.
Our research results offer a novel systematic perspective for iridology studies
and promote the progress of both theoretical and practical work in iris
diagnosis.
PMID- 23144042
TI - Estimation and prediction of drug therapy on the termination of atrial
fibrillation by autoregressive model with exogenous inputs.
AB - Atrial fibrillation (AF) is the most frequent cardiac arrhythmia seen in clinical
practice. Several therapeutical approaches have been developed to terminate the
AF and the effects are evaluated by the reduction of the wavelet number after the
treatments. Most of the previous studies focus on modeling and analysis the
mechanism, and the characteristic of AF. But no one discusses about the
prediction of the result after the drug treatment. This paper is the first study
to predict whether the drug treatment for AF is active or not. In this paper, the
linear autoregressive model with exogenous inputs (ARX) that models the system
output-input relationship by solving linear regression equations with least
squares method was developed and applied to estimate the effects of
pharmacological therapy on AF. Recordings (224-site bipolar recordings) of plaque
electrode arrays placed on the right and left atria of pigs with sustained AF
induced by rapid atrial-pacing were used to train and test the ARX models. The
cardiac mapping data from twelve pigs treated with intravenous administration of
antiarrhythmia drug, propafenone (PPF) or dl-sotalol (STL), was evaluated. The
recordings of cardiac activity before the drug treatment were input to the model
and the model output reported the estimated wavelet number of atria after the
drug treatment. The results show that the predicting accuracy rate corresponding
to the PPF and STL treatment was 100% and 92%, respectively. It is expected that
the developed ARX model can be further extended to assist the clinical staffs to
choose the effective treatments for the AF patients in the future.
PMID- 23144044
TI - Association of all-trans retinoic acid treatment with the renin-angiotensin
aldosterone system expression in glomerulosclerosis rats.
AB - BACKGROUND AND OBJECTIVE: All-trans retinoic acid (ATRA), a promising therapeutic
agent, has been confirmed in animal experiments as playing a protective role
against renal diseases. The renin-angiotensin aldosterone system (RAAS) plays a
key role in the pathogenesis of renal diseases, and RAAS inhibitors can prevent
the progression of kidney diseases. In our previous study, we found that ATRA
could play a protective role against glomerulosclerosis (GS) lesions in rats, and
its effect was similar to RAAS inhibitors. However, whether ATRA treatment was
associated with RAAS expression was not clear. METHODS: Six-week-old male Wistar
rats were divided into three groups: sham operation group (SHO),
glomerulosclerosis model group without treatment (GS) and GS model group treated
with ATRA (GA). At the end of 13 weeks, the relevant samples were collected and
analyzed. RESULTS: The mRNA and protein expression of angiotensin-converting
enzyme 1 (ACE1) in the GS group was notably higher when compared with the SHO
group. However, mRNA and protein expression of ACE1 in the ATRA treatment group
was markedly down-regulated when compared with the GS group. Angiotensin
converting enzyme 2 (ACE2) expression (mRNA or protein) in the GS group was
reduced compared with that in the SHO group, and ATRA markedly increased the mRNA
and protein expression of ACE2 compared with the GS group. The levels of protein
expression of angiotensin I and angiotensin II were significantly up-regulated in
the GS group compared with those in the SHO group, and ATRA reduced their
expression in the GA group when compared with the GS group. CONCLUSION: ATRA is
associated with RAAS expression in GS rats, but its detailed mechanism needs to
be elucidated by further research.
PMID- 23144045
TI - Variability in cadence during forced cycling predicts motor improvement in
individuals with Parkinson's disease.
AB - Variability in severity and progression of Parkinson's disease symptoms makes it
challenging to design therapy interventions that provide maximal benefit.
Previous studies showed that forced cycling, at greater pedaling rates, results
in greater improvements in motor function than voluntary cycling. The precise
mechanism for differences in function following exercise is unknown. We examined
the complexity of biomechanical and physiological features of forced and
voluntary cycling and correlated these features to improvements in motor function
as measured by the Unified Parkinson's Disease Rating Scale (UPDRS). Heart rate,
cadence, and power were analyzed using entropy signal processing techniques.
Pattern variability in heart rate and power were greater in the voluntary group
when compared to forced group. In contrast, variability in cadence was higher
during forced cycling. UPDRS Motor III scores predicted from the pattern
variability data were highly correlated to measured scores in the forced group.
This study shows how time series analysis methods of biomechanical and
physiological parameters of exercise can be used to predict improvements in motor
function. This knowledge will be important in the development of optimal exercise
based rehabilitation programs for Parkinson's disease.
PMID- 23144046
TI - The relationship between glycaemic variability and cardiovascular complications
in patients with acute myocardial infarction and type 2 diabetes: a report from
the DIGAMI 2 trial.
AB - AIMS: Hyperglycaemia during hospitalization for acute myocardial infarction (AMI)
is a risk predictor, but attempts to improve the prognosis by insulin-based
glucose control have not been consistently successful. Increased glycaemic
variability, a potential effect of insulin treatment, has been linked to a worse
prognosis in critically ill patients. The present aim was to study the
possibility of such a relation in patients with type 2 diabetes (T2DM) and AMI.
METHOD AND RESULTS: We studied 578 T2DM patients who had glucose levels measured
hourly while receiving an insulin-glucose infusion during the first 48 h of
hospitalization for AMI. Three measures of glycaemic variability: root mean
square error (RMSE), range, and slope were studied in relation to a composite
endpoint of mortality, stroke, and reinfarction and to mortality. In unadjusted
analyses, the mean level of glycaemic variability did not differ between patients
who died during 12 months of follow-up compared with those who survived. In a Cox
regression model adjusting for age and previous congestive heart failure, there
was no increased risk for the composite endpoint associated with increased
glycaemic variability; RMSE: hazard ratio (HR) 1.09 [95% confidence interval (CI)
0.93-1.27; P = 0.28], range: HR 1.01 (95% CI: 0.98-1.05; P = 0.47), and slope: HR
1.01 (95% CI: 0.99-1.04; P = 0.40). There was furthermore no increased risk in
mortality; RMSE HR 1.14 (95% CI: 0.93-1.38; P = 0.21), range HR 1.03 (95% CI:
0.98-1.08; P = 0.28), and slope HR 1.01 (95% CI: 0.98-1.04; P = 0.55).
CONCLUSION: The 1-year risk for death, reinfarction, or stroke did not relate to
glycaemic variability in T2DM patients with AMI treated with insulin infusion.
PMID- 23144047
TI - Prognostic role of persistent positive blood cultures after initiation of
antibiotic therapy in left-sided infective endocarditis.
AB - AIM: Persistent infection is not a scientific evidence-based definition. The
guidelines of infective endocarditis (IE) establish a cut-off point of 7-10 days,
which is arbitrary and probably too long. Our hypothesis is that persistent
positive blood cultures after 48-72 h from the initiation of antibiotic therapy
are associated with a worse prognosis in patients with left-sided IE. METHODS AND
RESULTS: We repeated blood cultures after 48-72 h of the initiation of the
antibiotic treatment in 407 patients with left-sided IE of a total of 692
episodes consecutively diagnosed from 1996 to 2011. We have compared the profile
of patients whose blood cultures became negative and those with persistent
positive blood cultures. We performed a multivariate logistic regression model to
determine the prognostic implication of persistent positive blood cultures. Of
256 patients with positive blood cultures at admission, 89 (35%) had persistent
positive cultures after 48-72 h from the initiation of the antibiotic treatment.
Persistent positive blood cultures (OR: 2.1; 95% CI: 1.2-3.6), age (OR: 1.026;
95% CI: 1.007-1.046), Staphylococcus aureus infection (OR: 3.3; 95% CI: 1.6-6.6),
heart failure (OR: 2.8; 95% CI: 1.6-4.7), and renal failure (OR: 2.9; 95% CI: 1.8
4.9) were found to be independently associated with higher in-hospital mortality.
CONCLUSIONS: The presence of persistent positive blood cultures is an independent
risk factor for in-hospital mortality which doubles the risk of death of patients
with left-sided IE. It should be taken into account in the risk stratification of
these patients.
PMID- 23144048
TI - Resistant hypertension: a frequent and ominous finding among hypertensive
patients with atherothrombosis.
AB - AIMS: The effect of resistant hypertension on outcomes in patients with
atherothrombotic disease is currently unknown. Accordingly, we sought to
determine the prevalence and outcomes of resistant hypertension in stable
hypertensive outpatients with subclinical or established atherothombotic disease
enrolled in the international Reduction of Atherothrombosis for Continued Health
(REACH) registry. METHODS AND RESULTS: Resistant hypertension was defined as a
blood pressure >=140/90 mmHg at baseline (>=130/80 mmHg if diabetes/renal
insufficiency) with the use of >=3 antihypertensive medications, including a
diuretic. The primary outcome was a composite of cardiovascular death, myocardial
infarction, or stroke at 4 years. A total of 53 530 hypertensive patients were
included. The prevalence of resistant hypertension was 12.7%; 6.2% on 3
antihypertensive agents, 4.6% on 4 agents, and 1.9% on >=5 agents (mean: 4.7 +/-
0.8). In addition to a diuretic, these patients were being treated mostly with
ACE-inhibitors/angiotensin receptor blockers (90.1%), beta-blockers (67.0%), and
calcium channel blockers (50.8%). Patients with resistant hypertension had a
higher risk of the primary endpoint on multivariable analysis [hazard ratio (HR)
1.11, 95% confidence interval (CI) 1.02-1.20; P = 0.017], including an increased
non-fatal stroke risk (HR: 1.26; 95% CI: 1.10-1.45; P = 0.0008). Hospitalizations
due to congestive heart failure were higher (P < 0.0001). Patients on >=5 agents
had a higher adjusted risk for the primary endpoint when compared with those on
<=3 agents (P = 0.03). CONCLUSION: The presence of resistant hypertension
identifies a subgroup of patients with hypertension and atherothrombosis who are
at heightened risk for adverse long-term outcomes.
PMID- 23144050
TI - Virus-induced appearance of the selectin ligand sLeX in herpes simplex virus type
1-infected T-cells: involvement of host and viral factors.
AB - Circulating leukocytes that express selectin ligands such as the carbohydrate
epitope sialyl Lewis X (sLeX) may interact with endothelial selectins, resulting
in transmigration of the leukocyte across the endothelial wall to adjacent
tissue. Due to the potential of selectin-ligand interactions as targets in viral
pathogenesis, we aimed at determining whether herpes simplex virus type 1 (HSV1)
is able to induce the appearance of sLeX at the surface of infected leukocytes.
We found that HSV1 infection of a T-cell line resulted in transcriptional
activation of human fucosyltransferase genes FUT3, FUT6 and FUT7, the two latter
genes encoding the fucosyltransferases rate limiting for sLeX synthesis. Flow
cytometry and confocal microscopy demonstrated that HSV1 infection resulted in a
2-fold rise in the proportion of sLeX-positive cells. Increased levels of FUT3,
FUT6 and FUT7 RNA were detected already at 3 h post infection, and treatment with
cycloheximide, a translation inhibitor, blocked a HSV1-induced increase in the
expression of FUT3, FUT6 and FUT7 RNA, suggesting involvement of viral or
cellular proteins. Studies with infectious viral mutants indicated that the viral
immediate early (alpha) protein ICP0 is essential for the initiation of FUT7
though not for FUT3 or FUT6 transcription. In CD3+ cells, derived from peripheral
blood mononuclear cells, HSV1 infection induced expression of FUT3, FUT5 and
FUT6, whereas FUT7 was not altered. The mean sLeX fluorescence intensity of CD3+
cells was significantly higher in HSV1-infected CD3+ cells. This suggests that
infected leukocytes during HSV1 viremia may express selectin ligands with
possible but as yet unproven roles in viral pathogenesis.
PMID- 23144051
TI - The prenatal care at school program.
AB - School absenteeism and poor compliance with prenatal appointments are concerns
for pregnant teens. The Prenatal Care at School (PAS) program is a new model of
prenatal care involving local health care providers and school personnel to
reduce the need for students to leave school for prenatal care. The program
combines prenatal care and education designed specifically for adolescents.
Twenty-eight girls attended PAS in the fall of 2010. Program evaluation results
showed a 14.2% increase in school attendance among students enrolled compared to
peers enrolled the previous year, a 5.7% increase over a local teen clinic's
attendance to their group prenatal care program, and a 42% increase in pregnancy
and childbirth knowledge. Satisfaction surveys indicated that participants all
believed that PAS helped prepare them for labor and delivery and 92% felt
encouraged to stay in school. This pilot program benefited pregnant teens by
increasing school educational time, improving preparation for labor and delivery,
and increasing participation with prenatal care.
PMID- 23144052
TI - Inconsistent placebo effects in NICE's network analysis.
PMID- 23144053
TI - High urinary ACE2 concentrations are associated with severity of glucose
intolerance and microalbuminuria.
AB - OBJECTIVE: Angiotensin-converting enzyme 2 (ACE2) plays an important role in
glucose metabolism and renal function. However, the relationship between ACE2 and
hyperglycemia or microalbuminuria has not been established in humans. We
investigated whether urinary ACE2 levels are associated with abnormal glucose
homeostasis and urinary albumin excretion. METHODS: We developed an ELISA for
quantifying ACE2 in urine. The ELISA was used to measure urinary ACE2 levels in
621 subjects with: normal glucose tolerance (NGT; n=77); impaired fasting glucose
(IFG) or impaired glucose tolerance (IGT) (n=132); and type 2 diabetes mellitus
(T2DM, n=412). Insulin resistance was assessed by homeostasis model assessment
for insulin resistance (HOMA-IR) index and urinary albumin excretion by urine
albumin-to-creatinine ratio (ACR). Other biochemical and anthropometric
parameters were measured. RESULTS: Urinary ACE2 levels were significantly higher
in insulin-resistant subjects with IFG, IGT, and T2DM than in the NGT group
(P<0.001). Urinary ACE2 concentrations appeared to correlate with HOMA-IR,
fasting blood glucose, triglyceride, high-sensitivity C-reactive protein, serum
creatinine, urinary ACR, and systolic blood pressure (all P<0.05). After
adjustment for impaired renal function and other metabolic parameters, urinary
ACE2 concentration was still associated with a higher risk for T2DM (OR 1.80, 95%
CI 1.05-3.08, P=0.02). In addition, urinary ACE2 levels were highly predictive of
microalbuminuria after adjusting for clinical risk factors (OR 2.68, 95% CI 1.55
4.64, P<0.001). CONCLUSION: Our data suggest that the urinary ACE2 level is
closely associated with T2DM and is an independent risk factor for
microalbuminuria.
PMID- 23144054
TI - Bone marrow-mesenchymal stem cells are a major source of interleukin-7 and
sustain colitis by forming the niche for colitogenic CD4 memory T cells.
AB - OBJECTIVE: Interleukin (IL)-7 is mainly produced in bone marrow (BM) that forms
the niche for B cells. We previously demonstrated that BM also retains pathogenic
memory CD4 T cells in murine models of inflammatory bowel disease (IBD). However,
it remains unknown whether BM-derived IL-7 is sufficient for the development of
IBD and which cells form the niche for colitogenic memory CD4 T cells in BM.
DESIGN: To address these questions, we developed mice in which IL-7 expression
was specific for BM, and identified colitis-associated IL-7-expressing
mesenchymal stem cells (MSC) in the BM. RESULTS: IL-7-/-*RAG-1-/- mice injected
with BM cells from IL-7+/+*RAG-1-/- mice, but not from IL-7-/-*RAG-1-/- mice,
expressed IL-7 in BM, but not in their colon, and developed colitis when injected
with CD4+CD45RBhigh T cells. Cultured BM MSC stably expressed a higher level of
IL-7 than that of primary BM cells. IL-7-sufficient, but not IL-7-deficient, BM
MSC supported upregulation of Bcl-2 in, and homeostatic proliferation of,
colitogenic memory CD4 T cells in vitro. Notably, IL-7-/-*RAG-1-/- mice
transplanted with IL-7-sufficient, but not IL-7-deficient, BM MSC expressed IL-7
in BM, but not in their colon, and developed colitis when transplanted with
CD4+CD45RBhigh T cells. CONCLUSIONS: We demonstrate for the first time that BM
MSC are a major source of IL-7 and play a pathological role in IBD by forming the
niche for colitogenic CD4 memory T cells in BM.
PMID- 23144055
TI - Liver disease progression and virological response: entecavir rescue still
possible in the setting of rtM204I lamivudine-resistant mutation.
PMID- 23144061
TI - Specific learning disability and its newest definition: which is comprehensive?
And which is insufficient?
AB - The American Psychiatric Association's proposed definition of specific learning
disability ("specific learning disorder") for the DSM-5 reflects current thinking
and best practice in learning disabilities. It continues the core
conceptualization of learning disability (LD) as well as proposes identification
criteria to supplant the discredited aptitude-achievement discrepancy formula.
Improvements can be found along with long-standing and new controversies about
the nature of LD. The proposed definition both provides a model of a currently
acceptable definition and reflects critical issues in the operationalization of
LD that the field continues to neglect.
PMID- 23144056
TI - Whither the attenuated psychosis syndrome?
PMID- 23144062
TI - Rethinking ADHD and LD in DSM-5: proposed changes in diagnostic criteria.
AB - The Diagnostic and Statistical Manual of Mental Disorders (DSM) is currently
undergoing revision that will lead to a fifth edition (DSM-5) in 2013. This
article first provides a brief synopsis of the DSM-5 administrative structure,
procedures, and guiding principles to enhance understanding of how changes are
made in the DSM. The next two sections (on attention-deficit/hyperactivity
disorder and learning disorders, respectively) highlight the major concerns and
controversies surrounding the DSM-IV diagnostic criteria for these two disorders
and provide a rationale for the proposed changes to the criteria, along with a
commentary on the empirical evidence on which the proposed changes were based.
PMID- 23144063
TI - Comorbidity of LD and ADHD: implications of DSM-5 for assessment and treatment.
AB - Attention-deficit/hyperactivity disorder (ADHD) and learning disability (LD) can
co-occur for a significant minority of children with each disorder. A total of 17
studies (2001-2011) examining ADHD-LD comorbidity were reviewed, revealing a
higher mean comorbidity rate (45.1%) than has been obtained previously. Higher
comorbidity may be the result of including students with writing disorders, not
just reading and/or math disabilities. Proposed DSM-5 criteria for both disorders
will likely affect comorbidity rates; however, it is unclear whether such rates
will increase or decrease. Regardless of the specific impact of DSM revisions,
academic skill and/or performance deficits should be assessed for students with
ADHD as part of screening, comprehensive evaluation, and treatment monitoring.
Comprehensive intervention services for students with comorbid ADHD and LD will
require empirically supported treatment strategies that address both disorders
and that are implemented across school and home settings.
PMID- 23144064
TI - Culprit lesion remodelling and long-term prognosis in patients with acute
coronary syndrome: an intravascular ultrasound study.
AB - AIMS: Positive arterial remodelling is recognized as one of the morphological
characteristics of the vulnerable plaque. Limited data are available on a long
term outcome of acute coronary syndrome (ACS) patients with culprit lesion
positive arterial remodelling (PR). The aim of this study was to investigate the
long-term impact of culprit lesion PR in patients with ACS. METHODS AND RESULTS:
In 134 patients with ACS, intravascular ultrasound (IVUS) was performed to assess
target lesion remodelling before percutaneous coronary intervention. PR was
defined as the ratio of the external elastic membrane cross-sectional area at the
target lesion to that of at the proximal reference of >1.05, and intermediate or
negative remodelling (IR/NR) was defined as that of <=1.05. Major adverse cardiac
event (MACE) was defined as a composite of death, ACS, and target lesion
revascularization. During the follow-up (median 5.8 years), MACE-free survival
was significantly lower in the PR group than that in the IR/NR group (log-rank, P
= 0.005). Survival and ACS-free survival were also significantly lower in the PR
group than that in the IR/NR group (log-rank, both P = 0.04). By multivariable
Cox regression analysis, PR (hazard ratio = 2.4, P = 0.02) and diabetes (hazard
ratio = 1.9, P = 0.03) were independent predictors of MACE. CONCLUSION: Culprit
lesion PR was associated with a poor long-term prognosis in patients with ACS. PR
may be a marker of vulnerable patients.
PMID- 23144065
TI - Giant aortic pseudoaneurysm presented with acute coronary syndrome by compressing
the coronary arterial system.
PMID- 23144066
TI - The enigma of decreased creatinine generation in acute kidney injury.
PMID- 23144067
TI - Dialysis Duration: The longer the better, but why? [corrected].
PMID- 23144068
TI - Nephrolithiasis and urinary tract infections: 'the chicken or the egg' dilemma?
PMID- 23144069
TI - Parvalbumin: calcium and magnesium buffering in the distal nephron.
AB - Parvalbumin (PV) is a classical member of the EF-hand protein superfamily that
has been described as a Ca(2+) buffer and Ca(2+) transporter/shuttle protein and
may also play an additional role in Mg(2+) handling. PV is exclusively expressed
in the early part of the distal convoluted tubule in the human and mouse kidneys.
Recent studies in Pvalb knockout mice revealed a role of PV in the distal
handling of electrolytes: the lack of PV was associated with a mild salt-losing
phenotype with secondary aldosteronism, salt craving and stronger bones compared
with controls. A link between the Ca(2+)-buffering capacity of PV and the
expression of the thiazide-sensitive Na(+)-Cl(-) cotransporter was established,
which could be relevant to the regulation of sodium transport in the distal
nephron. Variants in the PVALB gene that encodes PV have been described, but
their relevance to kidney function has not been established. PV is also
considered a reliable marker of chromophobe carcinoma and oncocytoma, two
neoplasms deriving from the distal nephron. The putative role of PV in tumour
genesis remains to be investigated.
PMID- 23144070
TI - Systems biology: building a useful model from multiple markers and profiles.
AB - The pathophysiology of diabetic nephropathy (DN) is driven by a complex, multi
facetted interplay of numerous molecular processes (protective as well as
damaging) and the balance between these, rather than the activity of a single
pathway, determines clinical presentation and outcome. We present a concept for
deriving a biomarker panel aimed to represent the relevant processes involved.
Our approach rests on a hybrid gene/protein interaction network that holds ample
information on molecular features (nodes) and their relations (edges), as a
result providing a basic structure to navigate in molecular content and context
being identified as relevant in DN. Extensive literature search on omics studies
in DN provided a molecular feature list mapping to a total of 2175 unique protein
coding genes [13 from single nucleotide polymorphisms (SNPs), 12 as targets from
relevant miRNAs, 1583 from transcriptomics, 5 from proteomics and 53 from
metabolomics via linking to enzymes; 509 features were identified from multiple
sources]. Two hundred and eighty-seven further human protein-coding genes
associated with DN were derived from searching NCBI Pubmed (utilizing MeSH and
gene-to-pubmed). Text mining of patents and clinical trial descriptors in the
context of DN further added about 1,000 features. These data were used to label
the respective nodes in the interaction network, as a result obtaining a DN
specific subgraph. Application of a segmentation algorithm on this subgraph
allowed the identification of DN-specific molecular units, each characterizing a
cluster of genes/proteins with a high internal functional association. We
interpret each such unit as a functionally relevant molecular process
contributing to the presentation of DN, and the total set of such units as a
molecular model of DN. We propose that selecting appropriate biomarkers from each
unit might allow the description of a patient's specific 'type' of DN, ultimately
leading to a better stratification of patients regarding progression risk and
optimal interventional approach.
PMID- 23144071
TI - Screening for chronic kidney disease can be of help to prevent atherosclerotic
end-organ damage.
AB - Atherosclerotic damage to the kidney is one of the most prevalent causes of
chronic kidney disease and ultimately kidney failure. It frequently coincides
with atherosclerotic damage to the heart, the brain and the lower extremities. In
fact, the severity of the damage in the various end organs runs in parallel. As
damage to the kidney is easy to measure by monitoring albuminuria and eGFR, and
as the early phases of kidney damage frequently precede the alarming
symptomatology in the heart, brain and peripheral vasculature, we argue that the
nephrologist should consider taking the lead in better organizing early detection
and management of CKD. The nephrologist can guide the general practitioner and
general health care workers to offer better preventive care to the subjects at
risk of progressive atherosclerotic end-organ damage.
PMID- 23144072
TI - Economic evaluation of different treatment modalities in acute kidney injury.
AB - BACKGROUND: Major controversy exists regarding the preferred treatment option for
acute kidney injury (AKI). The purpose of this study was to assess the
incremental cost-effectiveness of continuous renal replacement therapy (CRRT)
versus intermittent renal replacement therapy (IRRT) and conservative (CONS) AKI
treatment in Belgium. METHODS: An area-under-the-curve model based on survival
analysis was used to estimate costs and health outcomes using a 2-year time
horizon. Input data were derived from the multi-centre Stuivenberg Hospital Acute
Renal Failure 4 study. RESULTS: Analyses indicated that in-hospital mortality,
hospitalization costs and hospital length of stay differed significantly between
treatment modes. Follow-up mortality rates and follow-up cost per day showed no
significant difference between the treatment modes. Utility values, which
improved gradually after admission to the hospital, revealed no significant
differences between the three treatment strategies. CONS treatment was associated
with a 2-year cost of 33,802? and 0.54 quality-adjusted life years (QALYs). The
CRRT was the most expensive therapy with a cost of 51,365? leading to 0.57 QALYs.
The cost and QALYs associated with IRRT were 43,445? and 0.50, respectively. One
way sensitivity analyses indicated the 'in-hospital mortality' as the variable
with the greatest influence on the results. Probabilistic sensitivity analysis
resulted in a significant difference in treatment costs but no significant
difference in QALY gain. CONCLUSIONS: This study has indicated that the most
expensive treatment (CRRT) associated with an incremental cost of approximately
?7920 generates only a minor non-significant increase in QALYs of 0.07 compared
with IRRT. Additionally, the results revealed that the RRTs did not result in a
significant increase in QALYs despite their higher cost compared with the CONS
treatment. From a health economic perspective, the latter seems to be the
preferred treatment strategy.
PMID- 23144073
TI - Serum level of fibroblast growth factor 23 in maintenance renal transplant
patients.
AB - BACKGROUND: The discovery of fibroblast growth factor 23 (FGF23) provides a new
conceptual framework that improves our understanding of the pathogenesis of post
transplant bone disease. Excess FGF23 is produced in the early post-transplant
period; levels return to normal in the months following transplant. However, few
manuscripts discuss FGF23 levels in stable long-term renal transplant recipients.
METHODS: We performed a cross-sectional observational study of 279 maintenance
kidney recipients with chronic kidney disease (CKD) Stages 1-4 and stable
allograft function who had received their transplant at least 12 months
previously. We calculated the estimated GFR (eGFR) using the MDRD4 equation.
RESULTS: FGF23, parathyroid hormone (PTH) and phosphorus values were higher in
more advanced stages, while the serum calcitriol levels and the phosphate
reabsorption rate were lower. A significant inverse correlation was found between
eGFR and FGF23 (r = -0.487; P < 0.001), PTH (r = -0.444; P < 0.001), serum
phosphate levels (r = -0.315; P < 0.001) and fractional excretion of magnesium (r
= -0.503; P < 0.001). Multivariable analysis showed that increased time on
corticosteroids (P < 0.001), PTH (P < 0.001), serum phosphate (P = 0.003),
decreased serum calcitriol (P = 0.049) and estimated glomerular filtration (P =
0.003) rate were associated with high FGF23 levels. In contrast with pre
transplant patients and first year post-transplant patients, higher FGF23 values
were not correlated with increased phosphate excretion. An elevated phosphate
reabsorption rate was associated with decreased PTH (P < 0.001) and calciuria (P
= 0.028) and increased serum calcitriol (P = 0.009), plasma bicarbonate (P =
0.024) and estimated glomerular filtration (P = 0.003). CONCLUSIONS: Serum FGF23
concentrations remain increased in long-term kidney graft recipients, even in the
early stages of CKD. It remains to be seen whether measures aimed at reducing
serum levels of PTH and phosphate and/or corticosteroid doses might help to lower
serum FGF23 and whether this will improve kidney recipient outcomes.
PMID- 23144074
TI - COL4A5-associated X-linked Alport syndrome in a female patient with early inner
ear deafness due to a mutation in MYH9.
AB - Alport syndrome (ATS) is a type-IV collagen inherited disorder, caused by
mutations in COL4A3 and COL4A4 (autosomal recessive) or COL4A5 (X-linked).
Clinical symptoms include progressive renal disease, eye abnormalities and high
tone sensorineural deafness. A renal histology very similar to ATS is observed in
a subset of patients affected by mutations in MYH9, encoding non-muscle-myosin
Type IIa--a cytoskeletal contractile protein. MYH9-associated disorders (May
Hegglin anomaly, Epstein and Fechtner syndrome, and others) are inherited in an
autosomal dominant manner and characterized by defects in different organs
(including eyes, ears, kidneys and thrombocytes). We describe here a 6-year-old
girl with haematuria, proteinuria, and early sensorineural hearing loss. The
father of the patient is affected by ATS, the mother by isolated inner ear
deafness. Genetic testing revealed a pathogenic mutation in COL4A5 (c.2605G>A) in
the girl and her father and a heterozygous mutation in MYH9 (c.4952T>G) in the
girl and her mother. The paternal COL4A5 mutation seems to account for the
complete phenotype of ATS in the father and the maternal mutation in MYH9 for the
inner ear deafness in the mother. It has been discussed that the interaction of
both mutations could be responsible for both the unexpected severity of ATS
symptoms and the very early onset of inner ear deafness in the girl.
PMID- 23144075
TI - Editor's snapshot: an unexpected duodenal finding.
PMID- 23144076
TI - The enteric serotonergic system is altered in patients with diverticular disease.
AB - OBJECTIVE: Disturbances of the enteric serotonergic system have been implicated
in several intestinal motility disorders. Patients with diverticular disease (DD)
have been reported to exhibit abnormal intestinal motility and innervation
patterns. Gene expression profiles of the serotonergic system and distribution of
the serotonin type 4 receptor (5HT-4R) were thus studied in patients with DD.
DESIGN: Colonic specimens from patients with DD and controls were subjected to
quantitative PCR for serotonin receptors 2B, 3A, 4, serotonin transporter and
synthesising enzyme tryptophan hydroxylase. Localisation of 5HT-4R was determined
by dual-label immunocytochemistry using smooth muscle actin (alpha-SMA) and pan
neuronal markers (PGP 9.5) and quantitative analysis was carried out. Site
specific gene expression analysis of 5HT-4R was assessed within myenteric ganglia
and muscle layers. Correlation of 5HT-4R with muscarinic receptors 2 and 3 (M2R,
M3R) messenger RNA expression was determined. RESULTS: 5HT-4R mRNA expression was
downregulated in the tunica muscularis and upregulated in the mucosa of patients
with DD, whereas the other components of the serotonergic system remained
unchanged. 5HT-4R was detected in ganglia and muscle layers, but was decreased in
the circular muscle layer and myenteric ganglia of patients with DD. 5HT-4R mRNA
expression correlated with M2R/M3R mRNA expression in controls, but not in
patients with DD. CONCLUSIONS: The serotonergic system is compromised in DD.
Altered expression of 5HT-4R at mRNA and protein levels may contribute to
intestinal motor disturbances reported in patients with DD. The findings support
the hypothesis that DD is associated and possibly promoted by an enteric
neuromuscular pathology.
PMID- 23144077
TI - Psychosocial care for persons affected by emergencies and major incidents: a
Delphi study to determine the needs of professional first responders for
education, training and support.
AB - BACKGROUND: The role of ambulance clinicians in providing psychosocial care in
major incidents and emergencies is recognised in recent Department of Health
guidance. The study described in this paper identified NHS professional first
responders' needs for education about survivors' psychosocial responses, training
in psychosocial skills, and continuing support. METHOD: Ambulance staff
participated in an online Delphi questionnaire, comprising 74 items (Round 1) on
7-point Likert scales. Second-round and third-round participants each received
feedback based on the previous round, and responded to modified versions of the
original items and to new items for clarification. RESULTS: One hundred and two
participants took part in Round 1; 47 statements (64%) achieved consensus. In
Round 2, 72 people from Round 1 participated; 15 out of 39 statements (38%)
achieved consensus. In Round 3, 49 people from Round 2 participated; 15 out of 27
statements (59%) achieved consensus. Overall, there was consensus in the
following areas: 'psychosocial needs of patients' (consensus in 34/37 items);
'possible sources of stress in your work' (8/9); 'impacts of distress in your
work' (7/10); 'meeting your own emotional needs' (4/5); 'support within your
organisation' (2/5); 'needs for training in psychosocial skills for patients'
(15/15); 'my needs for psychosocial training and support' (5/6). CONCLUSIONS:
Ambulance clinicians recognise their own education needs and the importance of
their being offered psychosocial training and support. The authors recommend
that, in order to meet patients' psychosocial needs effectively, ambulance
clinicians are provided with education and training in a number of skills and
their own psychosocial support should be enhanced.
PMID- 23144079
TI - A review of blood component usage in a large UK emergency department after
implementation of simple measures.
AB - OBJECTIVES: To review clinical indications and demographics of transfusion and
the patterns of blood component ordering, transfusion, wastage and traceability,
before (2007) and after (2011) implementation of simple improvement strategies.
METHODS: Retrospective case note review of all patients presenting to the Royal
Infirmary of Edinburgh (RIE) Emergency Department (ED) for whom a blood component
was requested and historic comparison. Improvement measures implemented between
2007 and 2011 included (1) formal staff education, (2) use of e-learning Module
One Safe Transfusion Practice (traceability update, Medicines and Healthcare
products Regulatory Agency (MHRA) traceability regulations and importance of
returning completed blood component tags), (3) an ED resuscitation room blood
fridge, (4) introduction of a dedicated ED transfusion consultant and ED
transfusion link nurse and (5) the presence of an ED consultant on the Hospital
Transfusion Group. RESULTS: Between 1st January and 31st December 2011, blood
components were requested for 255 patient episodes, totalling 1034 individual
units. 687 units (66.4%) of blood component were transfused, 248 components
(24.0%) were recycled, 90 components (8.7%) were discarded and nine units (0.9%)
were unaccounted for. There was a 64% reduction in blood component ordering (3209
vs 1034 units), a 39% reduction in blood component transfusion (1131 vs 687
units) and a 96% reduction in unaccounted units (214 vs 9 units) between 2007 and
2011. There was a rise in the median age of the patient for whom a transfusion
request was made from 63.9 years in 2007 to 67.0 years in 2011. CONCLUSIONS:
Blood component ordering, usage and traceability within the ED have improved
significantly since 2007 following implementation of simple strategies. The age
of ED transfusion recipients is increasing.
PMID- 23144078
TI - TRAIL conjugated to nanoparticles exhibits increased anti-tumor activities in
glioma cells and glioma stem cells in vitro and in vivo.
AB - Glioblastomas (GBM) are characterized by resistance to chemotherapy and
radiotherapy, and therefore, alternative therapeutic approaches are needed. TRAIL
induces apoptosis in cancer but not in normal cells and is considered to be a
promising anti-tumor agent. However, its short in vivo half-life and lack of
efficient administration modes are serious impediments to its therapeutic
efficacy. Nanoparticles (NP) have been used as effective delivery tools for
various anticancer drugs. TRAIL was conjugated to magnetic ferric oxide NP by
binding the TRAIL primary amino groups to activated double bonds on the surface
of the NP. The effect of NP-TRAIL was examined on the apoptosis of glioma cells
and self-renewal of glioma stem cells (GSCs). In addition, the ability of the NP
TRAIL to track U251 cell-derived glioma xenografts and to affect cell apoptosis,
tumor volume, and survival among xenografted rats was also examined. Conjugation
of TRAIL to NP increased its apoptotic activity against different human glioma
cells and GSCs, as compared with free recombinant TRAIL. Combined treatment with
NP-TRAIL and gamma-radiation or bortezomib sensitized TRAIL-resistant GSCs to NP
TRAIL. Using rhodamine-labeled NP and U251 glioma cell-derived xenografts, we
demonstrated that the NP-TRAIL were found in the tumor site and induced a
significant increase in glioma cell apoptosis, a decrease in tumor volume, and
increased animal survival. In summary, conjugation of TRAIL to NP increased its
apoptotic activity both in vitro and in vivo. Therefore, NP-TRAIL represents a
targeted anticancer agent with more efficient action for the treatment of GBM and
the eradication of GSCs.
PMID- 23144080
TI - Prehospital non-drug assisted intubation for adult trauma patients with a Glasgow
Coma Score less than 9.
AB - OBJECTIVES: Prehospital airway management for adult trauma patients remains
controversial. We sought to review the frequency that paramedic non-drug assisted
intubation or attempted intubation is performed for trauma patients in Ontario,
Canada, and determine its association with mortality. METHODS: We conducted a
retrospective cohort study using the Ontario Trauma Registry's Comprehensive Data
Set for 2002-2009. Eligible patients were greater than 16 years of age, had an
initial Glasgow Coma Score of less than 9 and were cared for by ground-based non
critical care paramedics. The primary outcome was mortality. Outcomes were
compared between patients undergoing prehospital intubation versus basic airway
management. Logistic regression analyses were used to quantify the association
between prehospital intubation and mortality. RESULTS: Of the 2229 patients
included in the analysis, 671 (30.1%) underwent prehospital intubation. Annual
rates of prehospital intubation declined from 33.7% to 14.0% (ptrend<0.0001) over
the study period. Unadjusted death rates were 66.0% versus 34.8% in the
intubation and basic airway groups, respectively (p<0.0001). Intubation in the
prehospital setting was associated with a heightened risk of mortality (adjusted
OR 2.8, 95% CI 1.1 to 7.6). CONCLUSIONS: Prehospital non-drug assisted intubation
for trauma is being performed less frequently in Ontario, Canada. Within our
study population, paramedic non-drug assisted intubation or attempted intubation
was associated with a heightened risk of mortality.
PMID- 23144081
TI - A novel clinical and imaging based score for predicting outcome prior to
endovascular treatment of acute ischemic stroke.
AB - INTRODUCTION: Outcome after stroke intervention remains disappointing, with only
30-50% of patients having a good outcome at 90 days. We sought to identify
important outcome prognosticators. METHODS: All consecutive patients that
presented with an acute anterior circulation ischemic stroke, with adequate CT
perfusion imaging, and that underwent emergency endovascular treatment at two
centers between January 1, 2009 and November 2011, were retrospectively reviewed.
Investigators estimated the percentage of the total ischemic tissue that had
decreased cerebral blood volume (CBV) compared with the total area with elevated
time to peak (the penumbra). Multivariate regression analyses were performed to
identify variables with prognostic significance and a scoring system was created.
RESULTS: 163 patients underwent endovascular treatment for acute ischemic stroke.
Outcome data were available in 147 patients (90.2%). A good outcome (modified
Rankin Scale score 0-2) occurred in 64 patients (43.5%). Age, National Institutes
of Health Stroke Scale (NIHSS) score and per cent decreased CBV scores were the
only variables that predicted prognosis on multivariate analyses. A score was
created (NAV score-NIHSS, age, volume) that awards points based on these three
factors: 2 points for an NIHSS score of >= 15, 1 point for age >= 70 years, and 1
point for decreased CBV of >= 50%. The NAV score was strongly correlated with
overall outcome (p<0.01): scores of 0, 1, 2, 3, and 4 were associated with 84%,
50%, 36%, 25%, and 8% chance of a good outcome at 90 days. CONCLUSIONS: We
introduced a simple three factor scoring system to help predict outcome in
patients deemed candidates for intra-arterial acute ischemic stroke intervention.
PMID- 23144082
TI - Caution during use of desmopressin in IPSS.
PMID- 23144093
TI - Rhinitis associated with allergic nasal granuloma in Jersey cattle.
PMID- 23144083
TI - Anxiety sensitivity as a predictor of acute subjective effects of smoking.
AB - INTRODUCTION: Anxiety sensitivity (i.e., AS; the degree to which one believes
that anxiety and its related sensations are harmful) is a stable trait that is
associated with habitual smoking. Yet, the mechanisms linking AS and smoking are
unclear. A promising hypothesis is that high-AS individuals are more sensitive to
the acute subjective reinforcing effects of smoking and are, therefore, more
prone to tobacco dependence. This study examined trait AS as a predictor of
several subjective effects of cigarette smoking. METHODS: Adult non-treatment
seeking smokers (N = 87; 10+ cigarettes/day) completed a measure of AS during a
baseline session. Prior to a subsequent experimental session, participants were
asked to smoke normally before their appointment. At the outset of that visit,
each participant smoked a single cigarette of their preferred brand in the
laboratory. Self-report measures of affect and cigarette craving were completed
before and after smoking, and post-cigarette subjective effect ratings were
provided. RESULTS: AS predicted greater increases in positive affect from pre- to
post-cigarette (beta = .30, p = .006) as well as greater smoking satisfaction and
psychological reward (beta = .23 to .48, ps < .03). Each of these effects
remained statistically significant after adjusting for anxiety symptom severity.
AS did not predict the degree of negative affect and craving suppression or post
cigarette aversive effects. CONCLUSIONS: These findings suggest that positive
reinforcement mechanisms may be particularly salient etiological processes that
maintain smoking in high-AS individuals.
PMID- 23144094
TI - Pulse antibiotic therapy: it's time to cut back.
PMID- 23144095
TI - Bovine TB and badger culling.
PMID- 23144096
TI - Reference intervals and working ferrets.
PMID- 23144098
TI - Inactivated poliovirus vaccine, the fog of uncertainty is lifting.
PMID- 23144099
TI - PALS update 2010.
AB - During the past decade, guidelines for cardiopulmonary resuscitation have focused
on the importance of high quality CPR. The purpose is to temporarily maintain a
circulation to vital organs until specialized treatment is available. In,
essence, it has been a revolution in pediatric resuscitation in terms of coming
full circle to the 1960s when basic CPR was first developed. A fifth component to
the pediatric chain of survival has been added with emphasis on integrated post
cardiac arrest care. With mounting scientific evidences, American Heart
Association published new Pediatric Advanced life support 2010 guidelines in
accordance with the established five yearly cycle of guideline changes.
PMID- 23144100
TI - Immune thrombocytopenic purpura: historical perspective, current status, recent
advances and future directions.
AB - Immune thrombocytopenic purpura (ITP) has witnessed many changes and updates over
the past decade. The definitions of disease subtypes, course and response to
treatment have all been standardized recently. Consequent to the lack of an
international consensus management guideline, wide variations exist in treatment
practice. This is now being addressed to an extent by the much awaited ITP
International Working Group 2010 recommendations. The pathophysiologic mechanisms
have been unfolded at cellular, molecular and humoral levels. As a result, many
recent advances have taken place in the management of this disorder. This review
revisits the history of evolution of ITP, summarizes the current recommendations
for management and lists the recent advances and future prospects in this field.
PMID- 23144101
TI - Ruptured sinus of Valsalva masquerading as rheumatic heart disease.
AB - Ruptured sinus of Valsalva is a rare lesion in pediatric age group. We are
reporting a twelve year old child with hyperdynamic circulation being diagnosed
and treated as Rheumatic heart disease.
PMID- 23144102
TI - Rituximab followed by mycophenolate mofetil in children with IgM nephropathy.
AB - IgM nephropathy presents with refractory nephrotic syndrome and its treatment is
a significant challenge for pediatricians. We present two patients with IgM
nephropathy and frequently relapsing nephrotic syndrome treated with rituximab
and subsequently mycophenolate mofetil. Both showed complete remission, which 24
to 30 months later, was still maintained. The role of mycophenolate mofetil
therapy in maintaining remission after successful treatment of rituximab in IgM
nephropathy needs to be examined.
PMID- 23144103
TI - Prevalence of asthma in urban school children in Jaipur, Rajasthan.
AB - A cross sectional survey of 3321 school going children (5-15 years) using
modified ISAAC questionnaire in Jaipur city showed 7.59% children to have asthma
(in last 12 months) and 8.4% wheezing in last 12 months. Only 5.3% children had
physician diagnosed asthma ever suggesting under diagnoses.
PMID- 23144104
TI - Changes in biochemical contents of expressed breast milk on refrigerator storage.
AB - To determine the biochemical integrity of refrigerated breast milk for 96 hours
at 4C, a longitudinal observational study done with fresh milk samples. It is
found that there were significant changes in pH, serum albumin and lactose
concentrations in breast milk though within normal range.
PMID- 23144105
TI - Profile of EBV associated infectious mononucleosis.
AB - During a 5 year period, 33 children (22 males) were diagnosed to have infectious
mononucleosis (M:F::2:1; age 9 mo-15 y). The common clinical features observed
were fever (100%), lymphadenopathy (84%) hepatosplenomegaly (81%), tonsillar
enlargement (45%), neck swelling (30%), upper respiratory symptoms (21%),
epitrochlear node enlargement (20%), vomiting and diarrhea (1%). Ten children had
complications; upper airway obstruction and hemophagocytic lymphohistocytosis
occurred in four each and septic shock in two. EBV associated infectious
mononucleosis in hospitalized children was found to affect mainly preschool
children and had a favorable prognosis.
PMID- 23144106
TI - Treating pediatric liver tumors in India a challenging proposition.
PMID- 23144107
TI - Good outcome with ATG in aplastic anemia: welcome news, though thought-provoking!
PMID- 23144108
TI - Eyelid myoclonia with absence seizure precipitated by carbamazepine therapy.
PMID- 23144109
TI - Camphor poisoning.
PMID- 23144110
TI - Widening the spectrum of services delivered by the NRC.
PMID- 23144111
TI - Changing profile of undernutrition and edematous severe acute malnutrition
(ESAM).
PMID- 23144112
TI - Steroid sensitive nephrotic syndrome and steroid toxicity: what to do next.
PMID- 23144114
TI - Congenital lymphedema: another unique and gender specific stigmata of tuberous
sclerosis?
PMID- 23144115
TI - Generalized benign acanthosis nigricans.
PMID- 23144116
TI - An infant with skin rash.
PMID- 23144117
TI - Rowell syndrome.
PMID- 23144118
TI - Pyogenic granuloma.
PMID- 23144119
TI - Subjective health complaints and psychosocial work environment among university
personnel.
AB - BACKGROUND: Questionnaires are often used to study health problems in working
populations. An association between self-reported symptoms and psychosocial
strain has been suggested, but results from such studies are difficult to
interpret, as a gender difference might be present. The knowledge in this area is
not clear. AIMS: To compare the prevalence of subjective health symptoms and
their relation to psychosocial work strain among men and women in different age
groups, all working as university staff. METHODS: A cross-sectional survey was
carried out among university personnel. The questionnaire included a subjective
health complaint inventory consisting of 29 items about subjective somatic and
psychological symptoms experienced during the last 30 days and psychosocial work
factors. Regression analyses were performed. RESULTS: In total, 172 (86%) of 201
eligible employees participated. Women had a higher prevalence of musculoskeletal
symptoms than men. Significant differences were found between the genders for
headaches, neck pain and arm pain. There was a significant relationship between
musculoskeletal symptoms and work strain for both genders. This was found for
both men and women below 40 years and among men above the age of 40. No
significant difference was found between genders regarding pseudoneurological,
gastrointestinal, allergic and flu-like symptoms. CONCLUSIONS: More female than
male university personnel reported musculoskeletal symptoms. The musculoskeletal
symptoms were associated with high work strain in both genders, but, for women,
this was limited to employees under the age of 40. The cause of this gender
difference is unknown.
PMID- 23144120
TI - Acute histoplasmosis in three Mexican sewer workers.
AB - We report the detection of high-titre anti-Histoplasma capsulatum IgM in the
serum of three young adult males occupationally exposed to bat guano. Multidrug
treatment with trimethoprim- sulfamethoxazole was started, followed by
ciprofloxacin, clarithromycin, metamizole sodium,
rifampicin/isoniazid/pyrazinamide, moxifloxacin and lastly amphotericin B and
ceftriaxone. Despite treatment the condition of one patient deteriorated, and he
died 23 days after exposure. The other two patients recovered after receiving
similar therapy with the addition of voriconazole. They are currently being
treated with itraconazole for a 1-year period.
PMID- 23144121
TI - Energy expenditure in US automotive technicians and occupation-specific cardiac
rehabilitation.
AB - BACKGROUND: The standard exercise protocol for patients in a traditional cardiac
rehabilitation (rehab) programme may not be adequate for preparing manual workers
for a safe return to work, as these activities bear little resemblance to the
physical movements and force exertion required in most industrial jobs. AIMS: To
measure the energy expenditure as metabolic equivalents (METs) required for
automotive technicians, to compare this MET level with that normally attained in
traditional cardiac rehab programmes and to suggest cardiac rehab exercises for
automotive technicians based on specificity of training. METHODS: Automotive
technicians who volunteered to participate had their MET levels measured while
they performed a defined series of work tasks in the service department of an
automobile dealership. Their daily walking distance was also determined. RESULTS:
Thirty-six of 95 eligible subjects participated; a response rate of 38%. Mean
peak MET level was 7.1, less than the 8 METs target training goal often used in
traditional cardiac rehab programmes. However, patients' outcome MET levels in
cardiac rehab are usually measured by a treadmill stress test, whereas the
subjects reached 7.1 METs while performing work tasks. The subjects walked an
average of 5 km during a normal workday. CONCLUSIONS: Because MET level
measurements are work specific, automotive technicians in a cardiac rehab
programme should strive to reach and maintain a level of >7 METs while performing
specific training exercises that mimic the work tasks they must do throughout the
day. They can also benefit from traditional endurance training such as treadmill
walking.
PMID- 23144122
TI - Transport through graphene quantum dots.
AB - We review transport experiments on graphene quantum dots and narrow graphene
constrictions. In a quantum dot, electrons are confined in all lateral
dimensions, offering the possibility for detailed investigation and controlled
manipulation of individual quantum systems. The recently isolated two-dimensional
carbon allotrope graphene is an interesting host to study quantum phenomena, due
to its novel electronic properties and the expected weak interaction of the
electron spin with the material. Graphene quantum dots are fabricated by etching
mono-layer flakes into small islands (diameter 60-350 nm) with narrow connections
to contacts (width 20-75 nm), serving as tunneling barriers for transport
spectroscopy. Electron confinement in graphene quantum dots is observed by
measuring Coulomb blockade and transport through excited states, a manifestation
of quantum confinement. Measurements in a magnetic field perpendicular to the
sample plane allowed to identify the regime with only a few charge carriers in
the dot (electron-hole transition), and the crossover to the formation of the
graphene specific zero-energy Landau level at high fields. After rotation of the
sample into parallel magnetic field orientation, Zeeman spin splitting with a g
factor of g ~ 2 is measured. The filling sequence of subsequent spin states is
similar to what was found in GaAs and related to the non-negligible influence of
exchange interactions among the electrons.
PMID- 23144123
TI - Engineered quantum dot single-photon sources.
AB - Fast, high efficiency and low error single-photon sources are required for the
implementation of a number of quantum information processing applications. The
fastest triggered single-photon sources to date have been demonstrated using
epitaxially grown semiconductor quantum dots (QDs), which can be conveniently
integrated with optical microcavities. Recent advances in QD technology,
including demonstrations of high temperature and telecommunications wavelength
single-photon emission, have made QD single-photon sources more practical. Here
we discuss the applications of single-photon sources and their various
requirements, before reviewing the progress made on a QD platform in meeting
these requirements.
PMID- 23144124
TI - Respiratory function and chemical exposures among female hairdressers in
Palestine.
AB - BACKGROUND: Hairdressers are exposed to chemicals and work tasks that may cause
respiratory symptoms. There is little awareness of occupational health among
hairdressing salons in Palestine. AIMS: To characterize respiratory symptoms,
lung function, and knowledge of exposure to hazards among female Palestinian
hairdressers. METHODS: Cross-sectional study of female hairdressers and controls
of female university students and staff. Working history and respiratory symptoms
were collected using questionnaire. Lung function was measured. Working
conditions were characterized in salons. RESULTS: A total of 170 hairdressers
from 56 salons and 170 controls participated. Nineteen per cent of the
hairdressers reported wheezing versus 11% in the control group. The mean forced
vital capacity was 3.31 l compared with 3.42 l for controls. Adjusting for age
and height, there was a forced expiratory volume in 1 s reduction of 0.093 l (95%
confidence interval (CI) = 0.06-0.15) comparing hairdressers with controls. A
small number of hairdressers used respiratory protective equipment, and
satisfactory ventilation in salons were lacking. CONCLUSIONS: Female hairdressers
had higher prevalence of reported asthma and respiratory symptoms than the
controls, but these differences reduced markedly when adjusted for age, height,
weight and years of education. They had lower lung function measurements than the
control group. Increasing the awareness of occupational health hazards and
improving the work conditions for the hairdressers in Palestine is needed.
Possible bias could be present as hairdressers might have over reported symptoms
or lung function measurements might be affected by differences in socioeconomic
status between the two groups.
PMID- 23144127
TI - Predation response of Vibrio fischeri biofilms to bacterivorus protists.
AB - Vibrio fischeri proliferates in a sessile, stable community known as a biofilm,
which is one alternative survival strategy of its life cycle. Although this
survival strategy provides adequate protection from abiotic factors, marine
biofilms are still susceptible to grazing by bacteria-consuming protozoa.
Subsequently, grazing pressure can be controlled by certain defense mechanisms
that confer higher biofilm antipredator fitness. In the present work, we
hypothesized that V. fischeri exhibits an antipredator fitness behavior while
forming biofilms. Different predators representing commonly found species in
aquatic populations were examined, including the flagellates Rhynchomonas nasuta
and Neobodo designis (early biofilm feeders) and the ciliate Tetrahymena
pyriformis (late biofilm grazer). V. fischeri biofilms included isolates from
both seawater and squid hosts (Euprymna and Sepiola species). Our results
demonstrate inhibition of predation by biofilms, specifically, isolates from
seawater. Additionally, antiprotozoan behavior was observed to be higher in late
biofilms, particularly toward the ciliate T. pyriformis; however, inhibitory
effects were found to be widespread among all isolates tested. These results
provide an alternative explanation for the adaptive advantage and persistence of
V. fischeri biofilms and provide an important contribution to the understanding
of defensive mechanisms that exist in the out-of-host environment.
PMID- 23144128
TI - Combinatorial mutagenesis and selection of improved signal sequences and their
application for high-level production of translocated heterologous proteins in
Escherichia coli.
AB - We previously designed the consensus signal peptide (CSP) and demonstrated that
it can be used to strongly stimulate heterologous protein production in
Escherichia coli. A comparative study using CSP and two bacterial signal
sequences, pelB and ompA, showed that the effect of signal sequences on both
expression level and translocation efficiency can be highly protein specific. We
report here the generation of CSP mutant libraries by a combinatorial mutagenesis
approach. Degenerated CSP oligonucleotides were cloned in frame with the 5' end
of the bla gene, encoding the mature periplasmic beta-lactamase released from its
native signal sequence. This novel design allows for a direct selection of
improved signal sequences that positively affect the expression level and/or
translocation efficiency of beta-lactamase, based on the ampicillin tolerance
level of the E. coli host cells. By using this strategy, 61 different CSP mutants
with up to 8-fold-increased ampicillin tolerance level and up to 5.5-fold
increased beta-lactamase expression level were isolated and characterized
genetically. A subset of the CSP mutants was then tested with the alternative
reporter gene phoA, encoding periplasmic alkaline phosphatase (AP), resulting in
an up to 8-fold-increased production level of active AP protein in E. coli.
Moreover, it was demonstrated that the CSP mutants can improve the production of
the medically important human interferon alpha2b under high-cell-density
cultivations. Our results show that there is a clear potential for improving
bacterial signal sequences by using combinatorial mutagenesis, and bioinformatics
analyses indicated that the beneficial mutations could not be rationally
predicted.
PMID- 23144129
TI - Characterization of a newly discovered symbiont of the whitefly Bemisia tabaci
(Hemiptera: Aleyrodidae).
AB - Bemisia tabaci (Hemiptera: Aleyrodidae) is a species complex containing >28
cryptic species, some of which are important crop pests worldwide. Like many
other sap-sucking insects, whiteflies harbor an obligatory symbiont, "Candidatus
Portiera aleyrodidarum," and a number of secondary symbionts. So far, six genera
of secondary symbionts have been identified in B. tabaci. In this study, we
report and describe the finding of an additional bacterium in the indigenous B.
tabaci cryptic species China 1 (formerly known as B. tabaci biotype ZHJ3).
Phylogenetic analysis based on the 16S rRNA and gltA genes showed that the
bacterium belongs to the Alphaproteobacteria subdivision of the Proteobacteria
and has a close relationship with human pathogens of the genus Orientia.
Consequently, we temporarily named it Orientia-like organism (OLO). OLO was found
in six of eight wild populations of B. tabaci China 1, with the infection rate
ranging from 46.2% to 76.8%. Fluorescence in situ hybridization (FISH) of B.
tabaci China 1 in nymphs and adults revealed that OLOs are confined to the
bacteriome and co-occur with "Ca. Portiera aleyrodidarum." The vertical
transmission of OLO was demonstrated by detection of OLO at the anterior pole end
of the oocytes through FISH. Quantitative PCR analysis of population dynamics
suggested a complex interaction between "Ca. Portiera aleyrodidarum" and OLO.
Based on these results, we propose "Candidatus Hemipteriphilus asiaticus" for the
classification of this symbiont from B. tabaci.
PMID- 23144130
TI - Comparative analysis of Leptospira strains isolated from environmental soil and
water in the Philippines and Japan.
AB - There have been few reports on the epidemiological analysis of environmental
Leptospira isolates. This is probably because the isolation of leptospires from
the environment was usually unsuccessful due to the overgrowth of contaminants
and the slow growth of Leptospira. In this study, we collected a total of 88
samples of soil and water from three sites: Metro Manila and Nueva Ecija,
Philippines (an area where Leptospira is now endemic), and Fukuoka, Japan (an
area where Leptospira was once endemic). We succeeded in isolating Leptospira
from 37 samples by using the novel combination of five antimicrobial agents
reported in 2011. The frequencies of positive isolation of Leptospira in the
Philippines and Japan were 40 and 46%, respectively. For Leptospira-positive
samples, five colonies from each sample were isolated and analyzed by pulsed
field gel electrophoresis (PFGE). The isolates from each area showed their
respective characteristics in phylogenetic trees based on the PFGE patterns. Some
isolates were closely related to each other across borders. Based on 16S rRNA
gene-based phylogenetic analysis, four isolates in Fukuoka were identified as a
pathogenic species, L. alstonii; however, its virulence had been lost. One
isolate from Nueva Ecija was identified as the intermediate pathogenic species
Leptospira licerasiae. Most of the isolates from the environment belonged to
nonpathogenic Leptospira species. We also investigated the strain variation among
the isolates in a puddle over 5 months. We demonstrated, using PFGE analysis,
that Leptospira survived in the wet soil on dry days and appeared in the surface
water on rainy days. These results showed that the soil could be a reservoir of
leptospires in the environment.
PMID- 23144131
TI - Physiological and metabolic effects of carbon monoxide oxidation in the model
marine bacterioplankton Ruegeria pomeroyi DSS-3.
AB - Ruegeria pomeroyi expresses carbon monoxide (CO) dehydrogenase and oxidizes CO;
however, CO has no effect on growth. Nuclear magnetic resonance (NMR) spectra
showed that CO has no effect on cellular metabolite profiles. These data support
ecosystem models proposing that, even though bacterioplankton CO oxidation is
biogeochemically significant, it has an insignificant effect on bacterioplankton
productivity.
PMID- 23144132
TI - Identification of gold nanoparticle-resistant mutants of Saccharomyces cerevisiae
suggests a role for respiratory metabolism in mediating toxicity.
AB - Positively charged gold nanoparticles (0.8-nm core diameter) reduced yeast
survival, but not growth, at a concentration of 10 to 100 MUg/ml. Among 17
resistant deletion mutants isolated in a genome-wide screen, highly significant
enrichment was observed for respiration-deficient mutants lacking genes encoding
proteins associated with the mitochondrion.
PMID- 23144133
TI - Influence of Salmonella enterica serovar enteritidis infection on the development
of the cecum microbiota in newly hatched chicks.
AB - Terminal restriction fragment length polymorphism and quantitative PCR showed
that the cecal microbiota of chicks up to the age of 21 days was dominated by
representatives of the orders Enterobacteriales, Clostridiales, and
Lactobacillales. Salmonella enterica serovar Enteritidis infection caused the
greatest changes in the gut microbiota when 1-day-old chicks were infected,
compared with the infection of 4- and 16-day-old chicks.
PMID- 23144134
TI - Induction of nitrate-dependent Fe(II) oxidation by Fe(II) in Dechloromonas sp.
strain UWNR4 and Acidovorax sp. strain 2AN.
AB - We evaluated the inducibility of nitrate-dependent Fe(II)-EDTA oxidation (NDFO)
in non-growth, chloramphenicol-amended, resting-cell suspensions of Dechloromonas
sp. strain UWNR4 and Acidovorax sp. strain 2AN. Cells previously incubated with
Fe(II)-EDTA oxidized ca. 6-fold more Fe(II)-EDTA than cells previously incubated
with Fe(III)-EDTA. This is the first report of induction of NDFO by Fe(II).
PMID- 23144135
TI - Clostridium carboxidivorans strain P7T recombinant formate dehydrogenase
catalyzes reduction of CO(2) to formate.
AB - Recombinant formate dehydrogenase from the acetogen Clostridium carboxidivorans
strain P7(T), expressed in Escherichia coli, shows particular activity towards
NADH-dependent carbon dioxide reduction to formate due to the relative binding
affinities of the substrates and products. The enzyme retains activity over 2
days at 4 degrees C under oxic conditions.
PMID- 23144136
TI - Heterologous carotenoid-biosynthetic enzymes: functional complementation and
effects on carotenoid profiles in Escherichia coli.
AB - A limited number of carotenoid pathway genes from microbial sources have been
studied for analyzing the pathway complementation in the heterologous host
Escherichia coli. In order to systematically investigate the functionality of
carotenoid pathway enzymes in E. coli, the pathway genes of carotenogenic
microorganisms (Brevibacterium linens, Corynebacterium glutamicum, Rhodobacter
sphaeroides, Rhodobacter capsulatus, Rhodopirellula baltica, and Pantoea
ananatis) were modified to form synthetic expression modules and then were
complemented with Pantoea agglomerans pathway enzymes (CrtE, CrtB, CrtI, CrtY,
and CrtZ). The carotenogenic pathway enzymes in the synthetic modules showed
unusual activities when complemented with E. coli. For example, the expression of
heterologous CrtEs of B. linens, C. glutamicum, and R. baltica influenced P.
agglomerans CrtI to convert its substrate phytoene into a rare product-3,4,3',4'
tetradehydrolycopene-along with lycopene, which was an expected product,
indicating that CrtE, the first enzyme in the carotenoid biosynthesis pathway,
can influence carotenoid profiles. In addition, CrtIs of R. sphaeroides and R.
capsulatus converted phytoene into an unusual lycopene as well as into
neurosporene. Thus, this study shows that the functional complementation of
pathway enzymes from different sources is a useful methodology for diversifying
biosynthesis as nature does.
PMID- 23144137
TI - Landscape and meteorological factors affecting prevalence of three food-borne
pathogens in fruit and vegetable farms.
AB - Produce-related outbreaks have been traced back to the preharvest environment. A
longitudinal study was conducted on five farms in New York State to characterize
the prevalence, persistence, and diversity of food-borne pathogens in fresh
produce fields and to determine landscape and meteorological factors that predict
their presence. Produce fields were sampled four times per year for 2 years. A
total of 588 samples were analyzed for Listeria monocytogenes, Salmonella, and
Shiga toxin-producing Escherichia coli (STEC). The prevalence measures of L.
monocytogenes, Salmonella, and STEC were 15.0, 4.6, and 2.7%, respectively. L.
monocytogenes and Salmonella were detected more frequently in water samples,
while STEC was detected with equal frequency across all sample types (soil,
water, feces, and drag swabs). L. monocytogenes sigB gene allelic types 57, 58,
and 61 and Salmonella enterica serovar Cerro were repeatedly isolated from water
samples. Soil available water storage (AWS), temperature, and proximity to three
land cover classes (water, roads and urban development, and pasture/hay grass)
influenced the likelihood of detecting L. monocytogenes. Drainage class, AWS, and
precipitation were identified as important factors in Salmonella detection. This
information was used in a geographic information system framework to hypothesize
locations of environmental reservoirs where the prevalence of food-borne
pathogens may be elevated. The map indicated that not all croplands are equally
likely to contain environmental reservoirs of L. monocytogenes. These findings
advance recommendations to minimize the risk of preharvest contamination by
enhancing models of the environmental constraints on the survival and persistence
of food-borne pathogens in fields.
PMID- 23144138
TI - The mangotoxin biosynthetic operon (mbo) is specifically distributed within
Pseudomonas syringae genomospecies 1 and was acquired only once during evolution.
AB - Mangotoxin production was first described in Pseudomonas syringae pv. syringae
strains. A phenotypic characterization of 94 P. syringae strains was carried out
to determine the genetic evolution of the mangotoxin biosynthetic operon (mbo).
We designed a PCR primer pair specific for the mbo operon to examine its
distribution within the P. syringae complex. These primers amplified a 692-bp DNA
fragment from 52 mangotoxin-producing strains and from 7 non-mangotoxin-producing
strains that harbor the mbo operon, whereas 35 non-mangotoxin-producing strains
did not yield any amplification. This, together with the analysis of draft
genomes, allowed the identification of the mbo operon in five pathovars
(pathovars aptata, avellanae, japonica, pisi, and syringae), all of which belong
to genomospecies 1, suggesting a limited distribution of the mbo genes in the P.
syringae complex. Phylogenetic analyses using partial sequences from housekeeping
genes differentiated three groups within genomospecies 1. All of the strains
containing the mbo operon clustered in groups I and II, whereas those lacking the
operon clustered in group III; however, the relative branching order of these
three groups is dependent on the genes used to construct the phylogeny. The mbo
operon maintains synteny and is inserted in the same genomic location, with high
sequence conservation around the insertion point, for all the strains in groups I
and II. These data support the idea that the mbo operon was acquired horizontally
and only once by the ancestor of groups I and II from genomospecies 1 within the
P. syringae complex.
PMID- 23144139
TI - Impact of long-term diesel contamination on soil microbial community structure.
AB - Microbial community composition and diversity at a diesel-contaminated railway
site were investigated by pyrosequencing of bacterial and archaeal 16S rRNA gene
fragments to understand the interrelationships among microbial community
composition, pollution level, and soil geochemical and physical properties. To
this end, 26 soil samples from four matrix types with various geochemical
characteristics and contaminant concentrations were investigated. The presence of
diesel contamination significantly impacted microbial community composition and
diversity, regardless of the soil matrix type. Clean samples showed higher
diversity than contaminated samples (P < 0.001). Bacterial phyla with high
relative abundances in all samples included Proteobacteria, Firmicutes,
Actinobacteria, Acidobacteria, and Chloroflexi. High relative abundances of
Archaea, specifically of the phylum Euryarchaeota, were observed in contaminated
samples. Redundancy analysis indicated that increased relative abundances of the
phyla Chloroflexi, Firmicutes, and Euryarchaeota correlated with the presence of
contamination. Shifts in the chemical composition of diesel constituents across
the site and the abundance of specific operational taxonomic units (OTUs; defined
using a 97% sequence identity threshold) in contaminated samples together suggest
that natural attenuation of contamination has occurred. OTUs with sequence
similarity to strictly anaerobic Anaerolineae within the Chloroflexi, as well as
to Methanosaeta of the phylum Euryarchaeota, were detected. Anaerolineae and
Methanosaeta are known to be associated with anaerobic degradation of oil-related
compounds; therefore, their presence suggests that natural attenuation has
occurred under anoxic conditions. This research underscores the usefulness of
next-generation sequencing techniques both to understand the ecological impact of
contamination and to identify potential molecular proxies for detection of
natural attenuation.
PMID- 23144140
TI - Taking the starch out of oral biofilm formation: molecular basis and functional
significance of salivary alpha-amylase binding to oral streptococci.
AB - alpha-Amylase-binding streptococci (ABS) are a heterogeneous group of commensal
oral bacterial species that comprise a significant proportion of dental plaque
microfloras. Salivary alpha-amylase, one of the most abundant proteins in human
saliva, binds to the surface of these bacteria via specific surface-exposed alpha
amylase-binding proteins. The functional significance of alpha-amylase-binding
proteins in oral colonization by streptococci is important for understanding how
salivary components influence oral biofilm formation by these important dental
plaque species. This review summarizes the results of an extensive series of
studies that have sought to define the molecular basis for alpha-amylase binding
to the surface of the bacterium as well as the biological significance of this
phenomenon in dental plaque biofilm formation.
PMID- 23144142
TI - Multiplex PCR assay targeting a diguanylate cyclase-encoding gene, cgcA, to
differentiate species within the genus Cronobacter.
AB - In a comparison to the widely used Cronobacter rpoB PCR assay, a highly specific
multiplexed PCR assay based on cgcA, a diguanylate cyclase gene, that identified
all of the targeted six species among 305 Cronobacter isolates was designed. This
assay will be a valuable tool for identifying suspected Cronobacter isolates from
food-borne investigations.
PMID- 23144141
TI - Osmoprotection of Bacillus subtilis through import and proteolysis of proline
containing peptides.
AB - Bacillus subtilis can attain cellular protection against the detrimental effects
of high osmolarity through osmotically induced de novo synthesis and uptake of
the compatible solute l-proline. We have now found that B. subtilis can also
exploit exogenously provided proline-containing peptides of various lengths and
compositions as osmoprotectants. Osmoprotection by these types of peptides is
generally dependent on their import via the peptide transport systems (Dpp, Opp,
App, and DtpT) operating in B. subtilis and relies on their hydrolysis to
liberate proline. The effectiveness with which proline-containing peptides confer
osmoprotection varies considerably, and this can be correlated with the amount of
the liberated and subsequently accumulated free proline by the osmotically
stressed cell. Through gene disruption experiments, growth studies, and the
quantification of the intracellular proline pool, we have identified the PapA
(YqhT) and PapB (YkvY) peptidases as responsible for the hydrolysis of various
types of Xaa-Pro dipeptides and Xaa-Pro-Xaa tripeptides. The PapA and PapB
peptidases possess overlapping substrate specificities. In contrast,
osmoprotection by peptides of various lengths and compositions with a proline
residue positioned at their N terminus was not affected by defects in the PapA
and PapB peptidases. Taken together, our data provide new insight into the
physiology of the osmotic stress response of B. subtilis. They illustrate the
flexibility of this ubiquitously distributed microorganism to effectively exploit
environmental resources in its acclimatization to sustained high-osmolarity
surroundings through the accumulation of compatible solutes.
PMID- 23144145
TI - Alzheimer's disease--emerging new potential therapeutic modalities.
PMID- 23144143
TI - A new, sensitive marine microalgal recombinant biosensor using luminescence
monitoring for toxicity testing of antifouling biocides.
AB - In this study, we propose the use of the marine green alga Ostreococcus tauri,
the smallest free-living eukaryotic cell known to date, as a new luminescent
biosensor for toxicity testing in the environment. Diuron and Irgarol 1051, two
antifouling biocides commonly encountered in coastal waters, were chosen to test
this new biosensor along with two degradation products of diuron. The effects of
various concentrations of the antifoulants on four genetic constructs of O. tauri
(based on genes involved in photosynthesis, cell cycle, and circadian clock) were
compared using 96-well culture microplates and a luminometer to automatically
measure luminescence over 3 days. This was compared to growth inhibition of O.
tauri wild type under the same conditions. Luminescence appeared to be more
sensitive than growth inhibition as an indicator of toxicity. Cyclin-dependent
kinase (CDKA), a protein involved in the cell cycle, fused to luciferase (CDKA
Luc) was found to be the most sensitive of the biosensors, allowing an accurate
determination of the 50% effective concentration (EC(50)) after only 2 days
(diuron, 5.65 +/- 0.44 MUg/liter; Irgarol 1015, 0.76 +/- 0.10 MUg/liter). The
effects of the antifoulants on the CDKA-Luc biosensor were then compared to
growth inhibition in natural marine phytoplankton. The effective concentrations
of diuron and Irgarol 1051 were found to be similar, indicating that this
biosensor would be suitable as a reliable ecotoxicological test. The advantage of
this biosensor over cell growth inhibition testing is that the process can be
easily automated and could provide a high-throughput laboratory approach to
perform short-term toxicity tests. The ability to genetically transform and
culture recombinant O. tauri gives it huge potential for screening many other
toxic compounds.
PMID- 23144146
TI - Direct thrombin inhibitors' potential efficacy in Alzheimer's disease.
AB - Alzheimer's disease (AD) is a neurodegenerative disease with no available disease
modifying drugs. However, it has been postulated that neurovascular damage is a
primary occurrence in this disease. Neurovascular damage is the result of the
presence of cardiovascular risk factor generating hypoxia, oxidative stress, and
metabolic changes that activate the endothelial cells of the brain
microvasculature in order to respond to the stress by the development of
angiogenesis. This endothelial activation could lead to a secretion of many
proinflammatory cytokines and growth factors, such as thrombin. Heparin and
related oligosaccharides have been shown to be efficient in the improvement of
symptoms of AD. Their efficacy may be limited by their nonselective inhibitory
effect of thrombin's activity. Direct thrombin inhibitors, such as dabigatran,
might be efficient in the treatment of patients with AD because of their high
selectivity for thrombin's activity inhibition while having a safer side effects
profile than heparin.
PMID- 23144147
TI - Predicting attendance at dementia family support groups.
AB - This longitudinal study examined the predictors of dementia family caregivers'
self-reported attendance at support group meetings over 6 months. First-time
attendees were contacted by telephone after their first meeting and assessed for
(a) perceptions of similarity between themselves and other members, (b)
depressive symptoms, and (c) perceptions of social support from the facilitator
and other members. Participants (N = 70) were recontacted 6 months later to
obtain self-reports of attendance patterns. Self-reported attendance at any
meeting during this follow-up period was predicted by perceived similarity in
care recipient's stage of dementia and perceived support from group members as
assessed at the first interview. Greater perceived support from group members and
fewer depressive symptoms at time 1 predicted a higher frequency of support group
attendance over the follow-up period. Results have implications for orienting new
support group members as well as training and supporting group facilitators.
PMID- 23144149
TI - Occupational allergic rhinoconjunctivitis and bronchial asthma induced by goat
cheese.
PMID- 23144150
TI - The analysis of volatile organic compounds biomarkers for lung cancer in exhaled
breath, tissues and cell lines.
AB - BACKGROUND: Volatile organic compounds (VOCs) biomarkers in breath provide a
novel, noninvasive and quick approach to diagnosis lung cancer. The aim of the
proposed study was to investigate the VOCs biomarkers in exhaled breath for lung
cancer. METHOD: The VOCs in exhaled breath of 88 lung cancer patients, 70 lung
benign disease and 85 healthy people were analyzed by Solid Phase Micro
Extraction - Gas Chromatography Mass Spectrometry (SPME-GCMS). Three types of
lung cancer cells and 18 lung cancer patients' tissues were cultured in vitro.
The VOCs in the headspace of these cultivations were analyzed as an evidence of
production mechanism of the VOCs in breath. Three lung cancer diagnosis models
were constructed respectively in exhaled breath samples using Linear Discriminant
Analysis (LDA). Leave one out cross validation was employed to evaluate these
models. RESULTS: 23 VOCs, whose areas under curve (AUC) of receiver operating
characteristic (ROC) > 0.60 and p < 0.01, were confirmed as the VOCs biomarkers
for lung cancer. Three diagnostic models based on 23 VOCs could easily
discriminate lung cancer patients from controls with 96.47% sensitivity and
97.47% specificity. However, the discrimination between early stage and later
stage lung cancer was not very obvious.
PMID- 23144151
TI - Suppression of Zinc Finger Homeobox 3 expression in tumor cells decreases the
survival rate among non-small cell lung cancer patients.
AB - Zinc Finger Homeobox 3 (ZFHX3) was first identified as a suppressor of alpha
fetoprotein gene and is a good candidate for the 16q22 tumor suppressor. In this
study we investigated the relationship between tumoral ZFHX3 mRNA expression and
the clinicopathological characteristics of patients with non-small cell lung
cancer (NSCLC). We used semi-quantitative real time reverse transcription
polymerase chain reaction to assess expression of ZFHX3 mRNA in tumor samples
from 140 patients with NSCLC. We found that the 5-year overall survival rate
among patients weakly expressing ZFHX3 was significantly poorer than among those
expressing higher levels of ZFHX3 (P< 0.0001 by log-rank test). Multivariate
logistic regression analysis revealed being lower ZFHX3 expression are
independent predictors of lymph node metastasis. With low-ZFHX3 tumors, there was
a significantly (P=0.009) greater (7.39-fold higher) risk of lymph node
metastasis. Multivariate Cox proportional hazard analyses revealed that being
lower ZFHX3 expression (Hazard ratio, 4.42; 95% CI, 2.09-8.92; p=0.0002) were
independent factors affecting 5-year overall survival. Ratio of ZFHX3 mRNA in
tumor against normal lung in low-ZFHX3 tumor was lower than in high-ZFHX3 tumor.
In conclusion, suppression of ZFHX3 expression in tumor cells decreases the
survival rate among patients with NSCLC.
PMID- 23144152
TI - The interaction between RAGE gene polymorphisms and HPV infection in determining
the susceptibility of cervical cancer in a Chinese population.
AB - AIM: To explore the possible association between the receptor for advanced
glycation end products (RAGE) gene polymorphisms and the risk of cervical cancer.
METHOD: We enrolled 488 patients with cervical squamous cell carcinoma and 715
age-matched female healthy subjects as controls. Human Papillomavirus (HPV)
infection and four RAGE gene polymorphisms (-429T>C, -374T>A, 1704G>T, and 82G>S)
in all subjects were determined. RESULTS: The genotype distributions and allele
frequencies of -429T>C, 1704 T>G and -374T>A were not significantly different
between cervical cancer patients and controls (all P> 0.05). For 82G>S
polymorphisms, the genotype distributions and allele frequencies were
significantly different between the two groups. The cervical cancer patients had
markedly higher percentage of 82SS carriage than controls. The logistic
regression analysis showed that the 82SS genotype was associated with
significantly elevated risk for cervical cancer, adjusted odds ratio (OR) was
1.98, (P< 0.001). In addition, the 82SS carriers had significantly lower serum
soluble RAGE (sRAGE) levels than 82GS and 82GG. The polymorphisms of -429T>C,
374T>A and 1704T>G did not affect the cervical cancer risk and the serum sRAGE
levels. When all the cancer patients were stratified by HPV infection status, the
82GS and 82SS genotype carriers in the HPV infection subgroup had increased risk
for cervical cancer versus 82GG (OR=1.68 and 1.74, respectively, both P<0.05).
This trend was not observed in the subgroup with no detectable HPV DNA.
CONCLUSION: Our results suggest that the RAGE 82G>S polymorphisms, interacting
with HPV infection, are implicated in the occurrence of cervical cancer.
PMID- 23144153
TI - Association between newly identified variant form of DNA polymerase beta (Delta
208-304) and ovarian cancer.
AB - BACKGROUND: Base excision repair (BER) is a key pathway for maintaining genomic
stability. A key enzyme in the BER pathway is DNA polymerase beta (polbeta),
which removes the deoxyribose phosphate group (dRP) and fills in the gap with a
nucleotide after the DNA lesion is excised. It has been shown that more than
thirty percent of breast, bladder, esophageal, colon, and gastric cancer samples
studied so far have exhibited DNA polymerase beta mutation. AIM: To examine the
association between polbeta polymorphism and ovarian cancer, case control study
was performed using one hundred fifty two cancer samples and non-metastatic
normal samples from the same patients in Indian population. DESIGN: The polbeta
polymorphism was studied in ovarian carcinoma tissues samples initially by RT-PCR
followed by sequencing and then by western blot analysis. RESULT: A new type of
variant was detected along with the WT allele (polbetaDelta
=96.0%). LM was
the least sensitive test (87.4%) and had the lowest NPV (89.7%), but had the
highest specificity (99.1%) and positive predictive value (98.9%). For severe
falciparum malaria (prevalence 42.9%), the findings were similar. For non
falciparum severe malaria (prevalence 6.9%), no test had the WHO-recommended
sensitivity and specificity of >95% and >90%, respectively. RDTs were the least
sensitive (69.6%) and had the lowest NPV (96.7%). CONCLUSIONS: RDTs appear a
valuable point-of-care test that is at least equivalent to LM in diagnosing
severe falciparum malaria in this epidemiologic situation. None of the tests had
the required sensitivity/specificity for severe non-falciparum malaria but the
number of false-negative RDTs in this group was small.
PMID- 23144937
TI - A Bayesian interpretation of the particle swarm optimization and its kernel
extension.
AB - Particle swarm optimization is a popular method for solving difficult
optimization problems. There have been attempts to formulate the method in formal
probabilistic or stochastic terms (e.g. bare bones particle swarm) with the aim
to achieve more generality and explain the practical behavior of the method. Here
we present a Bayesian interpretation of the particle swarm optimization. This
interpretation provides a formal framework for incorporation of prior knowledge
about the problem that is being solved. Furthermore, it also allows to extend the
particle optimization method through the use of kernel functions that represent
the intermediary transformation of the data into a different space where the
optimization problem is expected to be easier to be resolved-such transformation
can be seen as a form of prior knowledge about the nature of the optimization
problem. We derive from the general Bayesian formulation the commonly used
particle swarm methods as particular cases.
PMID- 23144936
TI - Different levels of food restriction reveal genotype-specific differences in
learning a visual discrimination task.
AB - In behavioural experiments, motivation to learn can be achieved using food
rewards as positive reinforcement in food-restricted animals. Previous studies
reduce animal weights to 80-90% of free-feeding body weight as the criterion for
food restriction. However, effects of different degrees of food restriction on
task performance have not been assessed. We compared learning task performance in
mice food-restricted to 80 or 90% body weight (BW). We used adult wildtype (WT;
C57Bl/6j) and knockout (ephrin-A2-/-) mice, previously shown to have a reverse
learning deficit. Mice were trained in a two-choice visual discrimination task
with food reward as positive reinforcement. When mice reached criterion for one
visual stimulus (80% correct in three consecutive 10 trial sets) they began the
reverse learning phase, where the rewarded stimulus was switched to the
previously incorrect stimulus. For the initial learning and reverse phase of the
task, mice at 90%BW took almost twice as many trials to reach criterion as mice
at 80%BW. Furthermore, WT 80 and 90%BW groups significantly differed in
percentage correct responses and learning strategy in the reverse learning phase,
whereas no differences between weight restriction groups were observed in ephrin
A2-/- mice. Most importantly, genotype-specific differences in reverse learning
strategy were only detected in the 80%BW groups. Our results indicate that
increased food restriction not only results in better performance and a shorter
training period, but may also be necessary for revealing behavioural differences
between experimental groups. This has important ethical and animal welfare
implications when deciding extent of diet restriction in behavioural studies.
PMID- 23144938
TI - Postnatal ablation of Foxm1 from cardiomyocytes causes late onset cardiac
hypertrophy and fibrosis without exacerbating pressure overload-induced cardiac
remodeling.
AB - Heart disease remains a leading cause of morbidity and mortality in the
industrialized world. Hypertrophic cardiomyopathy is the most common genetic
cardiovascular disorder and the most common cause of sudden cardiac death. Foxm1
transcription factor (also known as HFH-11B, Trident, Win or MPP2) plays an
important role in the pathogenesis of various cancers and is a critical mediator
of post-injury repair in multiple organs. Foxm1 has been previously shown to be
essential for heart development and proliferation of embryonic cardiomyocytes.
However, the role of Foxm1 in postnatal heart development and in cardiac injury
has not been evaluated. To delete Foxm1 in postnatal cardiomyocytes, alphaMHC
Cre/Foxm1(fl/fl) mice were generated. Surprisingly, alphaMHC-Cre/Foxm1(fl/fl)
mice exhibited normal cardiomyocyte proliferation at postnatal day seven and had
no defects in cardiac structure or function but developed cardiac hypertrophy and
fibrosis late in life. The development of cardiomyocyte hypertrophy and cardiac
fibrosis in aged Foxm1-deficient mice was associated with reduced expression of
Hey2, an important regulator of cardiac homeostasis, and increased expression of
genes critical for cardiac remodeling, including MMP9, alphaSMA, fibronectin and
vimentin. We also found that following aortic constriction Foxm1 mRNA and protein
were induced in cardiomyocytes. However, Foxm1 deletion did not exacerbate
cardiac hypertrophy or fibrosis following chronic pressure overload. Our results
demonstrate that Foxm1 regulates genes critical for age-induced cardiomyocyte
hypertrophy and cardiac fibrosis.
PMID- 23144939
TI - In vivo open-bore MRI reveals region- and sub-arc-specific lengthening of the
unloaded human posterior cruciate ligament.
AB - Open-bore MRI scanners allow joint soft tissue to be imaged over a large,
uninterrupted range of flexion. Using an open-bore scanner, 3D para-sagittal
images of the posterior cruciate ligament (PCL) were collected from seven healthy
subjects in unloaded, recumbent knee extension and flexion. PCL length was
measured from one 2D MRI slice partition per flexion angle, per subject. The
anterior surface of the PCL lengthened significantly between extension and
flexion (p<0.001). Conversely, the posterior surface did not. Changes were not
due to the PCL moving relative to the 2D slice partition; measurements made from
3D reconstructions, which compensated for PCL movement, did not differ
significantly from measurements made from 2D slice partitions. In a second
experiment, videos of knee flexion were made by imaging two subjects at several
flexion angles. Videos allowed soft tissue tracking; examples are included. In a
third experiment, unloaded knees of seven healthy, recumbent subjects were imaged
at extension and at 40 degrees , 70 degrees , 90 degrees , 100 degrees , 110
degrees and 120 degrees flexion. The distance between PCL attachments increased
between extension and 100 degrees , and then decreased (p<0.001). The anterior
surface of the PCL lengthened over the flexion angles measured (p<0.01). The
posterior surface of the PCL lengthened between extension and 40 degrees and
then shortened (p<0.001). Both attachment separation and anterior surface length
increased dramatically between extension and 40 degrees , but varied less
afterwards. Results indicate that PCL dynamics differ between terminal extension
and active function sub-arcs. Also, attachment separation cannot predict the
lengthening of all parts of the PCL, nor can lengthening of one part of the PCL
predict the lengthening of another part. A potential connection between
lengthening and loading is discussed. We conclude that low-field MRI can assess
ligament lengthening during flexion, and that the dynamics of the PCL for any
given region and sub-arc should be measured directly.
PMID- 23144940
TI - Effect of aging and dietary salt and potassium intake on endothelial PTEN
(Phosphatase and tensin homolog on chromosome 10) function.
AB - Aging promotes endothelial dysfunction, defined as a reduction in bioavailable
nitric oxide (NO) produced by the endothelial isoform of nitric oxide synthase
(NOS3). This enzyme is critically regulated by phosphorylation by protein kinase
B (Akt), which in turn is regulated by the lipid phosphatase, PTEN. The present
series of studies demonstrated a reduction in bioavailable NO as the age of rats
increased from 1 to 12 months. At 12 months of age, rats no longer demonstrated
increases in phosphorylated NOS3 in response to high dietary salt intake.
Endothelial cell levels of PTEN increased with age and became refractory to
change with increased salt intake. In contrast to the reduction in NO production,
endothelial cell production of transforming growth factor-beta (TGF-beta)
relative to NO increased progressively with age. In macrovascular endothelial
cells, PTEN was regulated in a dose-dependent fashion by TGF-beta, which was
further regulated by extracellular [KCl]. When combined with prior studies, the
present series of experiments suggested an integral role for PTEN in endothelial
cell pathobiology of aging and an important mitigating function of TGF-beta in
endothelial PTEN regulation. The findings further supported a role for diet in
affecting vascular function through the production of TGF-beta and NO.
PMID- 23144941
TI - Prevalence and characteristics associated with malnutrition at hospitalization
among patients with acquired immunodeficiency syndrome in Brazil.
AB - BACKGROUND: Brazil's National STD/AIDS Program is considered a model of success
worldwide. However, AIDS-associated malnutrition continues in subgroups of
Brazilian patients despite access to free highly active antiretroviral therapy
(HAART). We aimed to identify the prevalence of malnutrition and associated
factors among patients hospitalized with AIDS. METHODS: We conducted a cross
sectional nutritional assessment among 127 adults hospitalized with AIDS in
Brazil's third largest city. Using anthropometric measurements, we determined the
prevalence of malnutrition (body mass index <18.5 kg/m2) at hospitalization.
Prevalence ratios of malnutrition by demographic, socioeconomic, and clinical
conditions were estimated using log-binomial regression. RESULTS: One-third of
participants were first informed of their HIV disease during the current
hospitalization and recent treatment interruption was common (71%) among those on
HAART. Forty-three percent were malnourished and 35% had severe weight loss at
admission. Patient characteristics independently associated with malnutrition
were older age (2% increased prevalence for each year; 95% confidence interval
[CI] 0-4%) and very low daily per capita household income. Living on for N = 1-6, which suggests the internal
rotation of the HCN molecule is becoming increasingly hindered.
PMID- 23145728
TI - 1,1-Diamino-2,2-dinitroethylene under high pressure-temperature.
AB - The structural phase stability of 1,1-diamino-2,2-dinitroethylene (FOX-7) has
been studied up to 10 GPa through isothermal compression at 100 degrees C and
200 degrees C using synchrotron mid- and far-infrared spectroscopy. During
isothermal compression at 100 degrees C changes are observed in vibrational
spectra with increase in pressure that are indicative of significant distortion
to monoclinic alpha phase or a possible structural transformation to a high
pressure alpha(') phase at 2.2 GPa and alpha(") phase at 6.1 GPa. At 200 degrees
C, for the far- and mid-IR regimes, the similar changes were observed at 2.1
(2.0) GPa and 5.3 (5.5) GPa, respectively. The observed change is nearly
isobaric, consistent with previously reported high pressure and room temperature
values, up to the highest temperature of 200 degrees C reached in our
experiments. Over the total P-T range investigated, up to ~10 GPa and 200
degrees C, we observed no evidence of sample decomposition. The observed changes
are partially reversible with only slight evidence of the high pressure
distortion remaining upon complete decompression. Additional isobaric heating at
1.07 GPa was performed in the mid-IR regime, which clearly revealed an onset of
decomposition at 360 degrees C. Further x-ray or neutron diffraction, which are
needed to fully resolve the cause of observed changes above 2 and 5 GPa, are
ongoing.
PMID- 23145729
TI - The Jahn-Teller effect in the electron momentum spectroscopy of ammonia.
AB - The 1e and 3a(1) bands of the ammonia molecule have been studied using the high
resolution electron momentum spectroscopy at impact energies of 1200 and 600 eV.
Several slices of 1e and 3a(1) bands in the different binding energy ranges were
selected, and their electron-momentum distributions were carefully compared. The
discernable difference among the distributions of the selected slices of the 1e
band shows that the Jahn-Teller effect indeed influences the electron momentum
distribution of the 1e orbital of ammonia.
PMID- 23145730
TI - The isotope dependence of dissociative recombination via the indirect mechanism.
AB - A recently derived analytic formula for the low-energy dissociative recombination
of molecular ions and electrons involving capture into vibrationally excited
Rydberg states provides a simple expression for the isotope dependence of the
process. This expression depends only on the ratio of the relevant vibrational
frequencies of the two isotopomers of interest and can therefore be evaluated
even without knowledge of the dynamical parameters required to determine the
recombination cross sections. The expression is used to predict the isotope
dependence for a number of molecular ions and the results are compared with
experiment. While the agreement with the experiment is generally quite
reasonable, discrepancies may indicate a breakdown of the assumptions used to
derive the cross section formula or potential inaccuracies in the experiments.
PMID- 23145731
TI - Towards understanding the nature of the intensities of overtone vibrational
transitions.
AB - The overtone vibrational transitions, i.e., transitions between states separated
by more than one vibrational quantum play important role in many fields of
physics and chemistry. The overtone transition is a purely quantum process
associated with the so-called dynamical tunneling [Heller, E. J., "The many faces
of tunneling," J. Phys. Chem. A 103(49), 10433-10444 (1999)] whose probability is
small as compared to the fundamental transition. The transition probability is
proportional to the Landau-Lifshitz tunneling factor similar to the Gamov factor
in nuclear physics. However, as opposed to the Gamov tunneling, the Landau
Lifshitz tunneling lacks any barrier to tunnel through: Its probability looks as
if the system were forced to "dive" under the barrier up to a point where the
transition can be performed without any change in momentum, hence with a high
probability, and then to "emerge back" in a new state. It follows that the
transition probability is associated with the shape of the potential in the
classically forbidden region in the same sense as the transition energy is
associated with the shape of the potential in the classically allowed region, as
implied by the Bohr-Sommerfeld quantization rule, and in the same sense as the
probability of the Gamov tunneling is associated with the shape of the potential
within the barrier region. As soon as the tunneling character of the transition
is recognized, the well-known extreme sensitivity of the overtone intensities to
small variations of the fitting function representing the molecular potential
[Lehmann, K. K. and Smith, A. M., "Where does overtone intensity come from?" J.
Chem. Phys. 93(9), 6140-6147 (1990)] becomes fully understood: Small variations
of the potential in the classical region, which do not affect the energy levels
significantly, cause large variations in the forbidden region and hence do affect
the tunneling factor. This dictates a clear strategy of constructing the
potential energy and dipole moment functions (PEF and DMF) capable of explaining
the data of vibrational spectroscopy and possessing a predictive power. In this
paper, we will show that, for stretching vibrations, knowledge of the inner wall
of the PEF is necessary to perform this task. Incorrect behavior of the PEF at
extremely small interatomic separations corresponding to energies well above the
dissociation limit results in an incorrect rate of the intensity falloff, hence a
rapid increase of discrepancies between the calculated and observed intensities
with overtone number. Analysis of experimental data on some di- and polyatomic
molecules and their interpretations is presented, which shows that neglecting the
tunneling nature of overtone transitions does not permit making predictions of
the intensities with a known uncertainty. A new approach has to be developed.
First of all, an ab initio PEF giving correct energy levels and having correct
behavior of the repulsive wall must be constructed; thereafter, an ab initio DMF
is invoked to explain the experimental data for lower (observed) transitions and
to predict the intensities of higher (not yet observed) transitions with
approximately the same accuracy as that for lower overtones. These ideas also
apply to radiationless deactivation of rare-earth and transition-metal ions in
laser media, which proceeds via overtone absorption of electronic energy by
medium local vibrations.
PMID- 23145732
TI - Sign preference in ion-induced nucleation: contributions to the free energy
barrier.
AB - We have performed a series of computer simulations using the AVUS-HR approach to
better understand the origin of the sign preference in ion-induced nucleation. In
particular, we emphasize the importance of distinguishing between the total
formation free energy of a cluster, and the nucleation free energy, which
involves only those steps contributing to the free energy barrier. We have
separately considered how the ion-water potential energy, the water-water
potential energy, and the entropy contribute to both the cluster formation free
energy, and the nucleation free energy. These simulations have shown that while
the ion-water potential energies make the largest contribution to the formation
free energy difference between positive and negative ions, the entropy is the
contribution leading to lower nucleation free energy barriers for negative ions.
The primary reason for this is the larger stable (but precritical) clusters
formed around negative ions. We have further shown that the distinction between
formation and nucleation free energies is of particular importance when comparing
small cations with larger anions where the formation free energies can be much
lower for the cationic clusters, even though the nucleation barriers are lower
for the anionic clusters.
PMID- 23145733
TI - Pairing of 1-hexyl-3-methylimidazolium and tetrafluoroborate ions in n-pentanol.
AB - Molecular dynamics simulations are obtained and analyzed to study pairing of 1
hexyl-3-methylimidazolium and tetrafluoroborate ions in n-pentanol, in particular
by evaluating the potential-of-mean-force between counter ions. The present
molecular model and simulation accurately predicts the dissociation constant K(d)
in comparison to experiment, and thus the behavior and magnitudes for the ion
pair potential-of-mean-force at molecular distances, even though the dielectric
constant of the simulated solvent differs from the experimental value by about
30%. A naive dielectric model does not capture molecule structural effects such
as multiple conformations and binding geometries of the Hmim(+) and BF(4)(-) ion
pairs. Mobilities identify multiple time-scale effects in the autocorrelation of
the random forces on the ions, and specifically a slow, exponential time-decay of
those long-ranged forces associated here with dielectric friction effects.
PMID- 23145734
TI - Phase diagram of the modified Lennard-Jones system.
AB - An investigation of the precise determination of melting temperature in the
modified Lennard-Jones system under pressure-free conditions [Y. Asano and K.
Fuchizaki, J. Phys. Soc. Jpn. 78, 055002 (2009)] was extended under finite
pressure conditions to obtain the phase diagram. The temperature and pressure of
the triple point were estimated to be 0.61 epsilon/k(B) and 0.0018(5)
epsilon/sigma(3), and those of the critical point were 1.0709(19) epsilon/k(B)
and 0.1228(20) epsilon/sigma(3), where epsilon and sigma are the Lennard-Jones
parameters for energy and length scales, respectively, and k(B) is the Boltzmann
constant. The potential used here has a finite attractive tail and does not
suffer from cutoff problems. The potential can thus be a useful standard in
examining statistical-mechanical problems in which different treatments for the
tail would lead to different conclusions. The present phase diagram will then be
a useful guide not only for equilibrium calculations but also for nonequilibrium
problems such as discussions of the limits of phase (in)stability.
PMID- 23145735
TI - Semiquantal molecular dynamics simulations of hydrogen-bond dynamics in liquid
water using multi-dimensional Gaussian wave packets.
AB - A semiquantal (SQ) molecular dynamics (MD) simulation method based on an extended
Hamiltonian formulation has been developed using multi-dimensional thawed
gaussian wave packets (WPs), and applied to an analysis of hydrogen-bond (H-bond)
dynamics in liquid water. A set of Hamilton's equations of motion in an extended
phase space, which includes variance-covariance matrix elements as auxiliary
coordinates representing anisotropic delocalization of the WPs, is derived from
the time-dependent variational principle. The present theory allows us to perform
real-time and real-space SQMD simulations and analyze nuclear quantum effects on
dynamics in large molecular systems in terms of anisotropic fluctuations of the
WPs. Introducing the Liouville operator formalism in the extended phase space, we
have also developed an explicit symplectic algorithm for the numerical
integration, which can provide greater stability in the long-time SQMD
simulations. The application of the present theory to H-bond dynamics in liquid
water is carried out under a single-particle approximation in which the variance
covariance matrix and the corresponding canonically conjugate matrix are reduced
to block-diagonal structures by neglecting the interparticle correlations. As a
result, it is found that the anisotropy of the WPs is indispensable for
reproducing the disordered H-bond network compared to the classical counterpart
with the use of the potential model providing competing quantum effects between
intra- and intermolecular zero-point fluctuations. In addition, the significant
WP delocalization along the out-of-plane direction of the jumping hydrogen atom
associated with the concerted breaking and forming of H-bonds has been detected
in the H-bond exchange mechanism. The relevance of the dynamical WP broadening to
the relaxation of H-bond number fluctuations has also been discussed. The present
SQ method provides the novel framework for investigating nuclear quantum dynamics
in the many-body molecular systems in which the local anisotropic fluctuations of
nuclear WPs play an essential role.
PMID- 23145736
TI - Molecular dynamics simulation of the spherical electrical double layer of a soft
nanoparticle: effect of the surface charge and counterion valence.
AB - Molecular dynamics simulations were performed to study the ion and water
distribution around a spherical charged nanoparticle. A soft nanoparticle model
was designed using a set of hydrophobic interaction sites distributed in six
concentric spherical layers. In order to simulate the effect of charged
functionalyzed groups on the nanoparticle surface, a set of charged sites were
distributed in the outer layer. Four charged nanoparticle models, from a surface
charge value of -0.035 C m(-2) to -0.28 C m(-2), were studied in NaCl and CaCl(2)
salt solutions at 1 M and 0.1 M concentrations to evaluate the effect of the
surface charge, counterion valence, and concentration of added salt. We obtain
that Na(+) and Ca(2+) ions enter inside the soft nanoparticle. Monovalent ions
are more accumulated inside the nanoparticle surface, whereas divalent ions are
more accumulated just in the plane of the nanoparticle surface sites. The
increasing of the the salt concentration has little effect on the internalization
of counterions, but significantly reduces the number of water molecules that
enter inside the nanoparticle. The manner of distributing the surface charge in
the nanoparticle (uniformly over all surface sites or discretely over a limited
set of randomly selected sites) considerably affects the distribution of
counterions in the proximities of the nanoparticle surface.
PMID- 23145737
TI - A van der Waals density functional study of chloroform and other trihalomethanes
on graphene.
AB - A computational study of chloroform (CHCl(3)) and other trihalomethanes (THMs)
adsorbed on graphene is presented. The study uses the van der Waals density
functional method to obtain adsorption energies and adsorption structures for
these molecules of environmental concern. In this study, chloroform is found to
adsorb with the H atom pointing away from graphene, with adsorption energy 357
meV (34.4 kJ/mol). For the other THMs studied the calculated adsorption energy
values vary from 206 meV (19.9 kJ/mol) for fluoroform (CHF(3)) to 404 meV (39.0
kJ/mol) for bromoform (CHBr(3)). The corrugation of graphene as seen by the THMs
is small, the difference in adsorption energy along the graphene plane is less
than 6 meV for chloroform.
PMID- 23145738
TI - Potassium spin polarization lifetime for a 30-carbon chain siloxane film.
AB - The siloxane film derived from the 30-carbon chain triacontyltrichlorosilane
(TCTS) is studied as an anti-relaxation coating for atomic vapor cells. The
longitudinal spin relaxation lifetime of optically pumped potassium atoms in the
presence of TCTS is measured and the average number of non-relaxing atom-wall
collisions, or bounces, enabled by the coated surface is determined. X-ray
photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) of TCTS were
performed to investigate changes in chemical states and surface morphology of
TCTS arising from K atom deposition on the film surface. TCTS was found to give
approximately 530 bounces. Following lifetime measurements, K2p signals were
clearly observed in XPS spectra. AFM images display non-preferential K deposition
on the TCTS surface, however additional AFM studies with a TCTS surface exposed
to Rb atoms show deposition occurs along surface defects. In agreement, Rb is
found to preferentially deposit along the step edges of an 18-carbon chain
monolayer film derived from 1-Octadecene. Finally, AFM indicates a much smoother
surface for a tetracontane coating relative to TCTS. The importance of siloxane
surface morphology versus film thickness with respect to coating performance is
discussed.
PMID- 23145739
TI - Attraction between neutral dielectrics mediated by multivalent ions in an
asymmetric ionic fluid.
AB - We study the interaction between two neutral plane-parallel dielectric bodies in
the presence of a highly asymmetric ionic fluid, containing multivalent as well
as monovalent (salt) ions. Image charge interactions, due to dielectric
discontinuities at the boundaries, as well as effects from ion confinement in the
slit region between the surfaces are taken fully into account, leading to image
generated depletion attraction, ion correlation attraction, and steric-like
repulsive interactions. We investigate these effects by employing a combination
of Monte Carlo simulation methods, including explicit-ion simulations (where all
electrostatic interactions are simulated explicitly) and implicit-ion simulations
(where monovalent ions are replaced by an effective screened electrostatic
potential between multivalent ions), as well as an approximate analytical theory.
The latter incorporates strong ion-image charge correlations, which develop in
the presence of high valency ions in the mixture. We show that the implicit-ion
simulations and the proposed analytical theory can describe the explicit
simulation results on a qualitative level, while excellent quantitative agreement
can be obtained for sufficiently large monovalent salt concentrations. The
resultant attractive interaction between the neutral surfaces is shown to be
significant, as compared with the usual van der Waals interactions between semi
infinite dielectrics, and can thus play an important role at the nano scale.
PMID- 23145740
TI - The structure of N2 adsorbed on the rumpled NaCl(100) surface--a combined LEED
and DFT-D study.
AB - The structure of N(2) physisorbed on the NaCl(100) single crystal surface is
investigated by means of quantitative low-energy electron diffraction (LEED) in
combination with dispersion corrected density functional theory (DFT-D). In the
temperature range between 20 K and 45 K, a p(1 * 1) structure is observed in the
LEED experiment. According to the structure analysis based on the measured
diffraction spot intensity profiles, the N(2) molecules are adsorbed over the
topmost Na(+) ions. The experimental distance of the lower nitrogen to the Na(+)
ion underneath is (2.55 +/- 0.07) A; the corresponding DFT-D value is 2.65 A. The
axes of the molecules are tilted (26 +/- 3) degrees with respect to the surface
normal, while in the zero Kelvin optimum structure from DFT-D, the molecules have
a perpendicular orientation. The experimental monolayer heat of adsorption,
deduced from a Fowler-Guggenheim kinetic model of adsorption is -(13.6 +/- 1.6)
kJ mol(-1), including a lateral molecule-molecule interaction energy of -(2.0 +/-
0.4) kJ mol(-1). The zero Kelvin adsorption energy from DFT-D, including zero
point energy correction, is -15.6 kJ mol(-1); the molecule-molecule interaction
is -2.4 kJ mol(-1). While the rumpling of the NaCl(100) surface is unchanged upon
adsorption of nitrogen, the best-fit root mean square thermal displacements of
the ions in the topmost substrate layer are significantly reduced.
PMID- 23145741
TI - Frictional properties of two alkanethiol self assembled monolayers in sliding
contact: odd-even effects.
AB - Using molecular dynamics simulation, we have investigated the structural effects
on the frictional properties of self assembled monolayers (SAM) of n-alkanethiols
[CH(3)(CH(2))(n-1)SH, n = 12-15] in SAM-SAM contacts attached on Au (111)
substrates. We have observed an odd-even effect where friction coefficient for
SAM-SAM contacts with n = odd showed consistently higher values than those with n
= even. This odd-even effect is independent of the sliding velocity and the
relative tilt directions of the SAMs, and persists over a much higher pressure
range than that reported before for SAM-Au contacts [L. Ramin and A. Jabbarzadeh,
Langmuir 28, 4102-4112 (2012)]. For odd systems higher gauche defects were shown
to be the possible source of high friction coefficient. Under the same load and
shear rates (comparable sliding velocities), SAM-SAM contacts show mostly higher
friction compared to SAM-Au contacts. For SAM-SAM contacts, a more significant
increase of friction occurs at higher shear rates due to a shift in the tilt
orientation angle. We show SAM-SAM contacts with misaligned relative tilt
orientation angle (~45 degrees -90 degrees ) have considerably lower friction
compared with those whose tilt orientation angles are almost aligned in the
opposite directions and parallel to the shear.
PMID- 23145742
TI - Looking deeper into the structure of mixed electric double layers near the point
of zero charge.
AB - Molecular simulations have been carried out using the Metropolis Monte Carlo
approach to investigate the structure of planar electric double layers containing
counterion mixture within the framework of the unrestricted primitive model. The
results reveal that near the point of zero charge, the rise of monovalent salt
drastically elevates the collapse of ions regardless of their polarity. In
particular, we fail to observe the formation of a strongly correlated liquid in
the first counterion layer due to favorable entropic effects, in contrast to the
early data from molecular dynamics simulations [corrected] for a spherical
electric double layer [R. Messina, E. Gonzalez-Tovar, M. Lozada-Cassou, and C.
Holm, Europhys. Lett. 60, 383 (2002)]. Moreover, the large size of coions is
found to be a pivotal factor in determining the reversal of electrophoretic
mobility. On the other hand, the repulsive image charge forces thoroughly
annihilate this peculiar reversal of mobility within the investigated scope of
concentrations, but exert no effect on the emergence of charge reversal. These
findings highlight potential applications of coion's characteristics to control
gene delivery and colloidal stability as well as to design viral packing and
polyelectrolyte self-assembly.
PMID- 23145743
TI - Methodological aspects of the quantum-chemical description of interface dipoles
at tetrathiafulvalene/tetracyanoquinodimethane interfaces.
AB - The formation of dipoles at interfaces between organic semiconductors is expected
to play a significant role in the operation of organic-based devices, though the
electronic processes at their origin have still to be clearly elucidated. Quantum
chemical calculations can prove very useful to shed light on such electronic
interfacial phenomena provided that a suitable theoretical approach is used. In
this context, we have performed calculations on small vertical stacks of TTF-TCNQ
molecules, first at the CAS-MRCI level to validate the use of single
determinantal approaches, then at the MP2 level set as a benchmark. Various
density functional theory (DFT) functionals have then been applied to larger
stacks, showing that long-range corrected functionals are required to reproduce
MP2 results taken as benchmark. Finally, the use of periodic boundary conditions
at the DFT level points to the huge impact of depolarization effects between
adjacent stacks.
PMID- 23145744
TI - Surface roughening in polymer blend thin films by lateral phase separation: a
thermodynamic mechanism.
AB - We use a phase portrait approach to study the phase equilibria of a symmetric
binary polymer blend confined between an attracting wall and a neutral wall. We
find multiple solutions for this wall regime where only one solution exists for
antisymmetric walls. We also argue that, when one wall is a free surface,
roughening of the free surface upon lateral phase separation is expected, since
thermodynamics alone implies that the coexisting phases should exist at different
heights to minimise energy. We focus on the graphical insight provided by this
phase portrait approach.
PMID- 23145745
TI - Scattering function of semiflexible polymer chains under good solvent conditions.
AB - Using the pruned-enriched Rosenbluth Monte Carlo algorithm, the scattering
functions of semiflexible macromolecules in dilute solution under good solvent
conditions are estimated both in d = 2 and d = 3 dimensions, considering also the
effect of stretching forces. Using self-avoiding walks of up to N = 25,600 steps
on the square and simple cubic lattices, variable chain stiffness is modeled by
introducing an energy penalty epsilon(b) for chain bending; varying q(b) = exp (
epsilon(b)/k(B)T) from q(b) = 1 (completely flexible chains) to q(b) = 0.005, the
persistence length can be varied over two orders of magnitude. For unstretched
semiflexible chains, we test the applicability of the Kratky-Porod worm-like
chain model to describe the scattering function and discuss methods for
extracting persistence length estimates from scattering. While in d = 2 the
direct crossover from rod-like chains to self-avoiding walks invalidates the
Kratky-Porod description, it holds in d = 3 for stiff chains if the number of
Kuhn segments n(K) does not exceed a limiting value n(K)(*) (which depends on the
persistence length). For stretched chains, the Pincus blob size enters as a
further characteristic length scale. The anisotropy of the scattering is well
described by the modified Debye function, if the actual observed chain extension
=1+ (10.6 vs. 10.9 months, p = 0.463) or as 3+
(8.6 vs. 10.8 months, p = 0.377). The multivariate analysis indicated that EGFR
status is not an independent prognostic factor (hazard ratio 0.85, 0.56 to 1.12,
p = 0.247). There were also no significant differences in overall survival when
patients were categorized according to median (p = 0.116) or quartile (p = 0.767)
distribution of EGFR mRNA gene expression. Similar distributions of progression
free survival according to EGFR status were observed. CONCLUSIONS: Unlike
different cancer types where EGFR-positive disease is associated with an adverse
prognostic value, EGFR positivity is not prognostic of patient outcome in
metastatic gastric or GE cancer.
PMID- 23153333
TI - Measuring students' approaches to learning in different clinical rotations.
AB - BACKGROUND: Many studies have explored approaches to learning in medical school,
mostly in the classroom setting. In the clinical setting, students face different
conditions that may affect their learning. Understanding students' approaches to
learning is important to improve learning in the clinical setting. The aim of
this study was to evaluate the Study Process Questionnaire (SPQ) as an instrument
for measuring clinical learning in medical education and also to show whether
learning approaches vary between rotations. METHODS: All students involved in
this survey were undergraduates in their clinical phase. The SPQ was adapted to
the clinical setting and was distributed in the last week of the clerkship
rotation. A longitudinal study was also conducted to explore changes in learning
approaches. RESULTS: Two hundred and nine students participated in this study
(response rate 82.0%). The SPQ findings supported a two-factor solution involving
deep and surface approaches. These two factors accounted for 45.1% and 22.5%,
respectively, of the variance. The relationships between the two scales and their
subscales showed the internal consistency and factorial validity of the SPQ to be
comparable with previous studies. The clinical students in this study had higher
scores for deep learning. The small longitudinal study showed small changes of
approaches to learning with different rotation placement but not statistically
significant. CONCLUSIONS: The SPQ was found to be a valid instrument for
measuring approaches to learning among clinical students. More students used a
deep approach than a surface approach. Changes of approach not clearly occurred
with different clinical rotations.
PMID- 23153334
TI - Mutational analysis of sulfite reductase hemoprotein reveals the mechanism for
coordinated electron and proton transfer.
AB - Sulfite reductase catalyzes the six-electron reduction of sulfite to sulfide. The
active site, found in the hemoprotein subunit (SiRHP), sits on the distal face of
a negatively charged porphyrinoid called siroheme whose central iron atom is
coupled to a proximal Fe(4)S(4) cluster. Four positively charged amino acids are
positioned around the active site cavity. Together, these two arginines (R83 and
R153) and two lysines (K215 and K217) mitigate the negative charge on the
siroheme macrocycle. They also serve as a cage around the distally bound anion
that tightens when substrate binds and an active site loop clamps down.
Structures of native SiRHP point to these amino acids as being important, but
their specific roles are ill-defined. Here, we have altered those four active
site amino acids and one amino acid on the flexible loop (N149) to probe their
roles in SiRHP activity. None of these positively charged residues is required
for electron transfer, but only R83S and N149W variants can produce a fully
reduced product. By measuring the electrons used per unit of reduced sulfur
released, we show that K215, R153, and K217 are responsible for intermediate and
late proton transfers, whereas N149 and R153 play a role in the structure of the
flexible loop that controls anion binding and release. R83 is primarily
responsible for siroheme binding. Together, the activities and structures of
these variants reveal specific roles for each in anion binding and in coupled
proton transfer that facilitates electron transfer.
PMID- 23153336
TI - Comparison of different amino-functionalization procedures on a selection of
metal oxide microparticles: degree of modification and hydrolytic stability.
AB - Amino-modified metal oxide materials are essential in a wide range of
applications, including chromatography, ion adsorption, and as biomaterials. The
aim of this study is to compare different functionalization techniques on a
selection of metal oxides (SiO(2), TiO(2), ZrO(2), and SnO(2)) in order to
determine which combination has the optimal properties for a certain application.
We have used the nanocasting approach to synthesize micrometer-sized TiO(2),
ZrO(2), and SnO(2) particles, which have similar morphologies and porosities as
the starting mesoporous SiO(2) microparticles (Lichroprep Si 60). These metal
oxides were subsequently functionalized by four different approaches, (a)
covalent bonding of 3-aminopropyltriethoxysilane (APTES), (b) adsorption of 2
aminoethyl dihydrogen phosphate (AEDP), (c) surface polymerization of aziridine
(AZ), and (d) electrostatic interaction of poly(ethylenimine) (PEI), to produce a
high surface coverage of amino groups on their surfaces. Scanning electron
microscopy, nitrogen physisorption, and X-ray diffraction were used to
characterize the unmodified metal oxide particles, while thermogravimetric
analysis, ninhydrin adsorption, and zeta potential titrations were applied to
gain insight into the successfulness of the various surface modifications.
Finally, the hydrolytic stability at pH 2 and 10 was investigated by zeta
potential measurements. Unfortunately, the AEDP approach was not able to produce
efficient amino-modification on any of the tested metal oxide surfaces. On the
other hand, modifications with APTES, aziridine, and PEI appeared to give fairly
stable amino-functionalizations at high pH values for all metal oxides, while
these modifications were easily detached at pH 2, with the exception of SnO(2),
where the AZ and PEI samples were stable up to 40 h. The results are expected to
give valuable insights into the possibility of replacing amino-modified silica
with more hydrolytically stable metal oxides in various application fields, for
example, chromatography and drug delivery.
PMID- 23153335
TI - Spatial accessibility of primary health care utilising the two step floating
catchment area method: an assessment of recent improvements.
AB - BACKGROUND: The two step floating catchment area (2SFCA) method has emerged in
the last decade as a key measure of spatial accessibility, particularly in its
application to primary health care access. Many recent 'improvements' to the
original 2SFCA method have been developed, which generally either account for
distance-decay within a catchment or enable the usage of variable catchment
sizes. This paper evaluates the effectiveness of various proposed methods within
these two improvement groups. Moreover, its assessment focuses on how well these
improvements operate within and between rural and metropolitan populations over
large geographical regions. RESULTS: Demonstrating these improvements to the
whole state of Victoria, Australia, this paper presents the first comparison
between continuous and zonal (step) decay functions and specifically their effect
within both rural and metropolitan populations. Especially in metropolitan
populations, the application of either type of distance-decay function is shown
to be problematic by itself. Its inclusion necessitates the addition of a
variable catchment size function which can enable the 2SFCA method to dynamically
define more appropriate catchments which align with actual health service supply
and utilisation. CONCLUSION: This study assesses recent 'improvements' to the
2SFCA when applied over large geographic regions of both large and small
populations. Its findings demonstrate the necessary combination of both a
distance-decay function and variable catchment size function in order for the
2SFCA to appropriately measure healthcare access across all geographical regions.
PMID- 23153337
TI - Induction of cognitive fatigue in MS patients through cognitive and physical
load.
AB - The objective of the study was to investigate whether cognitive fatigue in
patients with multiple sclerosis (MS) is a spontaneous phenomenon or whether it
can be provoked or exacerbated through cognitive effort and motor exercise.
Thirty two patients with definite MS and cognitive fatigue according to the
Fatigue Scale for Motor and Cognitive Functions (FSMC >= 22) performed attention
tests (alertness, selective, and divided attention subtests from the TAP test
battery for attention performance) twice during rest (baseline), and before and
after treadmill training and cognitive load (a standardised battery of
neuropsychological tests lasting 2.5 hours). Subjective exhaustion was assessed
with a 10-point rating scale. Tonic alertness turned out to be the most sensitive
test and showed significantly increased reaction times after treadmill training
and after cognitive load. Patients' subjective assessment of exhaustion (10-point
rating scale) and the objective test results were discrepant. In contrast,
healthy control subjects (N = 20) did not show any decline of performance in the
subtest alertness after cognitive or physical load. Data favour the concept that
fatigue is induced by physical and mental load. Discrepancies between subjective
and objective assessment offer therapeutic options. The common notion of a purely
"subjective" lack of physical and/or mental energy should be reconsidered.
PMID- 23153338
TI - Kinetic studies of Ni organic complexes using diffusive gradients in thin films
(DGT) with double binding layers and a dynamic numerical model.
AB - In situ deployments of diffusive gradients in thin films (DGT) can provide direct
information on complex dissociation rates in natural waters. Recent advances in
understanding the dynamics of the interactions of metal complexes within DGT
devices have highlighted the characteristics of the binding layer, but there are
few data to complement these theoretical developments. In this work the
penetration into the Chelex binding layer of complexes of Ni with
nitrilotriacetic (NTA) and Suwannee River fulvic and humic acids (FA and HA) in
solution at pH 7 was investigated by deployment of DGT devices with two
sequential binding layers, a "front" and a "back" layer. In Ni-NTA experiments,
the masses of Ni bound by the front and back binding layers were similar, as
predicted for slowly dissociating complexes. For Ni-FA/HA solutions, a higher
mass of Ni was taken up by the front binding layer, consistent with fast
dissociation from a high proportion of the binding sites. The ratio of Ni in the
front to back binding layers was significantly lower (p < 0.05) for solutions of
Ni-HA compared to those of Ni-FA, indicating that Ni-HA complexes are less labile
than Ni-FA complexes in similar solutions (FA = 10 mg L(-1) and HA = 8 mg L(-1)).
A dynamic numerical model of the complexes in a DGT system was used to estimate
the dissociation rate constants that provided the best agreement with the
experimental data. Values obtained of 2 +/- 0.5 * 10(-4) s(-1) for Ni-NTA and 2.5
* 10(-3) s(-1) for Ni-FA when FA = 20 mg L(-1) and 3.42 * 10(-4) s(-1) for Ni-HA
when HA = 8 mg L(-1), could be rationalized with current knowledge of the
dynamics of these systems. This approach can improve kinetic information
obtainable using DGT and widen the range of considered complex labilities.
PMID- 23153339
TI - Thermodynamics-hydration relationships within loops that affect G-quadruplexes
under molecular crowding conditions.
AB - We systematically investigated the effects of loop length on the conformation,
thermodynamic stability, and hydration of DNA G-quadruplexes under dilute and
molecular crowding conditions in the presence of Na(+). Structural analysis
showed that molecular crowding induced conformational switches of
oligonucleotides with the longer guanine stretch and the shorter thymine loop.
Thermodynamic parameters further demonstrated that the thermodynamic stability of
G-quadruplexes increased by increasing the loop length from two to four, whereas
it decreased by increasing the loop length from four to six. Interestingly, we
found by osmotic pressure analysis that the number of water molecules released
from the G-quadruplex decreased with increasing thermodynamic stability. We
assumed that base-stacking interactions within the loops not only stabilized the
whole G-quadruplex structure but also created hydration sites by accumulating
nucleotide functional groups. The molecular crowding effects on the stability of
G-quadruplexes composed of abasic sites, which reduce the stacking interactions
at the loops, further demonstrated that G-quadruplexes with fewer stacking
interactions within the loops released a larger number of water molecules upon
folding. These results showed that the stacking interactions within the loops
determined the thermodynamic stability and hydration of the whole G-quadruplex.
PMID- 23153340
TI - Heart rate variability and target organ damage in hypertensive patients.
AB - BACKGROUND: We evaluated the association between linear standard Heart Rate
Variability (HRV) measures and vascular, renal and cardiac target organ damage
(TOD). METHODS: A retrospective analysis was performed including 200 patients
registered in the Regione Campania network (aged 62.4 +/- 12, male 64%). HRV
analysis was performed by 24-h holter ECG. Renal damage was assessed by estimated
glomerular filtration rate (eGFR), vascular damage by carotid intima-media
thickness (IMT), and cardiac damage by left ventricular mass index. RESULTS:
Significantly lower values of the ratio of low to high frequency power (LF/HF)
were found in the patients with moderate or severe eGFR (p-value < 0.001).
Similarly, depressed values of indexes of the overall autonomic modulation on
heart were found in patients with plaque compared to those with a normal IMT (p
value <0.05). These associations remained significant after adjustment for other
factors known to contribute to the development of target organ damage, such as
age. Moreover, depressed LF/HF was found also in patients with left ventricular
hypertrophy but this association was not significant after adjustment for other
factors. CONCLUSIONS: Depressed HRV appeared to be associated with vascular and
renal TOD, suggesting the involvement of autonomic imbalance in the TOD. However,
as the mechanisms by which abnormal autonomic balance may lead to TOD, and,
particularly, to renal organ damage are not clearly known, further prospective
studies with longitudinal design are needed to determine the association between
HRV and the development of TOD.
PMID- 23153341
TI - An interview with Lucio G. Costa and Michael Aschner, section editors for
toxicology.
AB - Lucio G. Costa is currently Professor of Environmental and Occupational Health
Sciences at the School of Public Health at the University of Washington. Dr.
Costa is a renowned neurotoxicologist whose research interests are focused on
understanding the role of neurotoxic substances in neurodevelopmental disorders
and other neurological, neuropsychiatric and neurodegenerative diseases. Dr
Costa's research laboratory makes use of a variety of in vivo and in vitro cell
culture systems, transgenic animal models and imaging techniques to study the
cellular, biochemical and molecular mechanisms of neurotoxicity.Michael Aschner
is the Gray E. B. Stahlman Professor of Pediatrics and Pharmacology at Vanderbilt
University School of Medicine as well as a Senior Investigator at the Kennedy
Center for Research on Human Development. Dr Aschner's research group has a
particular interest in the neurobiology and physiology of astrocytes and the
signaling mechanisms associated with central nervous system injury. Dr Aschner's
laboratory studies metal uptake and distribution in the brain, investigating the
mechanisms of transport of methylmercury and manganese across the capillaries of
the blood-brain barrier. His research utilizes various experimental models (C.
elegans, tissue cultures and rodents) to understand the acute toxicity of
manganese deposition in the brains of human neonates.In this interview we find
out a little more about the key issues in the field of toxicology research.
PMID- 23153343
TI - Evidence about preventing cardiovascular disease.
PMID- 23153342
TI - Photodynamic control of bioactivity in a nanofiber matrix.
AB - Self-assembling peptide materials have been used extensively to mimic natural
extracellular matrices (ECMs) by presenting bioactive epitopes on a synthetic
matrix. Although this approach can facilitate a desired response from cells grown
in the matrix, it lacks the capacity for spatial or temporal regulation of the
presented signals. We describe here a photoresponsive, synthetic ECM using a
supramolecular platform composed of peptide amphiphiles (PAs) that self-assemble
into cylindrical nanofibers. A photocleavable nitrobenzyl ester group was
included in the peptide backbone using a novel Fmoc-amino acid that is compatible
with microwave-assisted solid-phase peptide synthesis. The placement of the
photolabile group on the peptide backbone enabled efficient removal of the ECM
derived cell adhesion epitope RGDS from PA molecules upon exposure to light (half
life of photolysis ~1.9 min) without affecting the nanofiber assembly.
Fibroblasts cultured on RGDS-presenting PA nanofiber substrates demonstrated
increased cell spreading and more mature focal adhesions compared with
unfunctionalized and control (RGES-presenting) surfaces, as determined by
immunostaining and cell morphological analysis. Furthermore, we observed an
arrest in fibroblast spreading on substrates containing a cleavable RGDS epitope
when the culture was exposed to light; in contrast, this dynamic shift in cell
response was absent when the RGDS epitope was attached to the PA molecule by a
light-insensitive control linker. Light-responsive bioactive materials can
contribute to the development of synthetic systems that more closely mimic the
dynamic nature of native ECM.
PMID- 23153344
TI - The effects of resistance training on cardiovascular disease risk factors in
postmenopausal women: a randomized-controlled trial.
AB - Our aim was to determine the effects of resistance training on cardiovascular
risk factors in postmenopausal women. Forty-five women were included in the
study. Resistance exercises were done with an intensity of 60% of 1-Repetition
Maximum, for 12 weeks. Heart rate, blood pressure, estimated peak VO(2), lipid
profiles, and homocysteine levels were evaluated. There were significant time and
group interactions for body mass index (p = .02), heart rate (p = .04), systolic
blood pressure (p = .03), estimated mean peak VO(2) (p = .00), and total
cholesterol (p = .00), but there were no interactions with other evaluated
parameters. Resistance training has beneficial effects on particular
cardiovascular risk factors in postmenopausal women.
PMID- 23153345
TI - Physical activity, weight, and waist circumference in midlife women.
AB - During midlife years, women are at risk of increasing body weight and waist
circumference. We evaluated changes in weight and waist circumference from
enrollment to 2 years later and examined the influence of physical activity level
on those changes among 232 women aged between 40 and 50. Weight increased
significantly for the entire sample. Those who increased their physical activity
from enrollment to 2 years later had the smallest increase in weight and had a
slight decrease in waist circumference. To maintain ideal weight and waist
circumference, midlife women should be encouraged to increase physical activity
before and during the menopausal transition.
PMID- 23153346
TI - Recovery of midlife women from myocardial infarction.
AB - We conducted this qualitative study to elicit the experiences of midlife women
who survived myocardial infarctions (MIs) and returned home to recover. We
selected a phenomenological research method based on the philosophy of Merleau
Ponty. The researcher interviewed eight women ranging in age from 45 to 65. The
interviews were transcribed and analyzed using the approach of Thomas and Pollio.
For the women in this study, figural themes of the experience of the MI and
recovery must be understood within the existential grounds of the body and
others. Themes included the following: (a) interference, (b) freedom/unfreedom,
(c) knowing/not knowing, and (d) living in fear. Based on the findings of this
study, we suggest that women need to be better educated before leaving the
hospital. Returning home post MI was a difficult time, and the women in this
study felt a support group for female MI survivors was needed.
PMID- 23153347
TI - Qatari women living with cardiovascular diseases-challenges and opportunities to
engage in healthy lifestyles.
AB - In Qatar, cardiovascular diseases are the leading causes of morbidity and
mortality. Cardiovascular diseases can be prevented and controlled by modifying
lifestyle risk behaviors. In this qualitative study, we investigate ways to
increase participation in physical activity, and to promote a healthy diet, and
nonsmoking behavior in Qatari women. Individual in-depth interviews were
conducted with 50 Arabic women. Participation in physical activity, observing a
healthy diet, and abstinence from smoking are desirable lifestyle practices among
Qatari women. Social support networks, cultural values, religion, changing
sociodemographic and economic conditions, heart disease, and a harsh climate
affect the ability of these women to pursue a healthy lifestyle.
PMID- 23153351
TI - Higher-order aberrations and anisometropia.
AB - PURPOSE/AIM: Myopia incidence is increasing around the world. Myopization is
considered to be caused by a variety of factors. One consideration is whether
higher-order aberrations (HOA) influence myopization. More knowledge of optics in
anisometropic eyes might give further insight into the development of refractive
error. MATERIALS AND METHODS: To analyze the possible influence of HOA on
refractive error development, we compared HOA between anisometropes and
isometropes. We analyzed HOA up to the 4th order for both eyes of 20
anisometropes (mean age: 43 +/- 17 years) and 20 isometropes (mean age: 33 +/- 17
years). HOA were measured with the Shack-Hartman i.Profiler (Carl Zeiss, Germany)
and were recalculated for a 4 mm pupil. Mean spherical equivalent (MSE) was based
on the subjective refraction. Anisometropia was defined as >=1 D interocular
difference in MSE. The mean absolute differences between right and left eyes in
spherical equivalent were 0.28 +/- 0.21 D in the isometropic group and 2.81 +/-
2.04 D in the anisometropic group. Interocular differences in HOA were compared
with the interocular difference in MSE using correlations. RESULTS: For
isometropes oblique trefoil, vertical coma, horizontal coma and spherical
aberration showed significant correlations between the two eyes. In
anisometropes, all analyzed higher-order aberrations correlated significantly
between the two eyes except oblique secondary astigmatism and secondary
astigmatism. When analyzing anisometropes and isometropes separately, no
significant correlations were found between interocular differences of higher
order aberrations and MSE. For isometropes and anisometropes combined, tetrafoil
correlated significantly with MSE in left eyes. CONCLUSIONS: The present study
could not show that interocular differences of higher-order aberrations increase
with increasing interocular difference in MSE.
PMID- 23153352
TI - Horizontal relaxing incisions limit false positives in thick Mohs sections.
PMID- 23153353
TI - Environmental health and household demographics impacting biosand filter
maintenance and diarrhea in Guatemala: an application of structural equation
modeling.
AB - In rural health development practice, engineers and scientists must recognize the
complex interactions that influence individuals' contact with disease-causing
pathogens and understand how household habits may impact the adoption and long
term sustainability of new technology. The goal of this study was to measure the
effect of various environmental health factors and household demographics on the
operation and maintenance of the Biosand filter (Centre for Affordable Water and
Sanitation Technology, Calgary, Alberta, Canada) and diarrhea health burden in
the region. In July and August 2010, randomized household surveys (n = 286) were
completed in rural Guatemala detailing water access, sanitation availability,
hygiene practice, socio-economic status, education level, filter operation and
maintenance, and diarrhea health burden of the home. A hypothesized structural
equation model was developed based on a review of published research and tested
using the surveyed data. Model-derived parameter estimates indicated that: (a)
proper personal hygiene practices significantly promote proper filter operation
and maintenance; and (b) higher household education level, proper filter
operation and maintenance, and improved water supply significantly reduce
diarrhea health burden. Additionally, a high level of unexplained variance in
diarrhea indicated the filter, though protective of health, is not the only
factor influencing diarrhea.
PMID- 23153354
TI - The role of outcome expectations in the generation of the feedback-related
negativity.
AB - The feedback-related negativity (FRN) is thought to index activity within the
midbrain dopaminergic reward-learning system, with larger FRN magnitudes observed
when outcomes are worse than expected. This view holds that the FRN is an index
of neural activity coding for prediction errors, and reflects activity that can
be used to adaptively alter future performance. Untested to date, however, is a
key prediction of this view: the FRN should not appear in response to negative
outcomes when outcome expectations are not allowed to develop. The current study
tests this assumption by eliciting FRNs to win and loss feedback in conditions of
participant choice, participant observation of computer choice, and, critically,
simple presentation of win or loss feedback in the absence of a predictive choice
cue. Whereas FRNs were observed in each of the conditions in which there was time
for an expectation to develop, no FRN was observed in conditions without
sufficient time for the development of an expectation. These results provide
empirical support for an untested but central tenet of the reinforcement learning
account of the genesis of the FRN.
PMID- 23153356
TI - Construction of crystalline 2D covalent organic frameworks with remarkable
chemical (acid/base) stability via a combined reversible and irreversible route.
AB - Two new chemically stable [acid and base] 2D crystalline covalent organic
frameworks (COFs) (TpPa-1 and TpPa-2) were synthesized using combined reversible
and irreversible organic reactions. Syntheses of these COFs were done by the
Schiff base reactions of 1,3,5-triformylphloroglucinol (Tp) with p
phenylenediamine (Pa-1) and 2,5-dimethyl-p-phenylenediamine (Pa-2), respectively,
in 1:1 mesitylene/dioxane. The expected enol-imine (OH) form underwent
irreversible proton tautomerism, and only the keto-enamine form was observed.
Because of the irreversible nature of the total reaction and the absence of an
imine bond in the system, TpPa-1 and TpPa-2 showed strong resistance toward acid
(9 N HCl) and boiling water. Moreover, TpPa-2 showed exceptional stability in
base (9 N NaOH) as well.
PMID- 23153355
TI - Concussive injury before or after controlled cortical impact exacerbates
histopathology and functional outcome in a mixed traumatic brain injury model in
mice.
AB - Traumatic brain injury (TBI) may involve diverse injury mechanisms (e.g., focal
impact vs. diffuse impact loading). Putative therapies developed in TBI models
featuring a single injury mechanism may fail in clinical trials if the model does
not fully replicate multiple injury subtypes, which may occur concomitantly in a
given patient. We report development and characterization of a mixed
contusion/concussion TBI model in mice using controlled cortical impact (CCI; 0.6
mm depth, 6 m/sec) and a closed head injury (CHI) model at one of two levels of
injury (53 vs. 83 g weight drop from 66 in). Compared with CCI or CHI alone,
sequential CCI-CHI produced additive effects on loss of consciousness (p<0.001),
acute cell death (p<0.05), and 12-day lesion size (p<0.05) but not brain edema or
48-h contusion volume. Additive effects of CHI and CCI on post-injury motor
(p<0.05) and cognitive (p<0.005) impairment were observed with sequential CCI-CHI
(83 g). The data suggest that concussive forces, which in isolation do not induce
histopathological damage, exacerbate histopathology and functional outcome after
cerebral contusion. Sequential CHI-CCI may model complex injury mechanisms that
occur in some patients with TBI and may prove useful for testing putative
therapies.
PMID- 23153357
TI - Mechanistic insights on organocatalytic enantioselective decarboxylative
protonation by epicinchona-thiourea hybrid derivatives.
AB - Mechanism and the origin of enantioselectivity in the decarboxylative protonation
of alpha-amino malonate hemiester promoted by epicinchona-thiourea hybrid
organocatalyst is established by using the DFT(M06-2X/6-311+G**//ONIOM2)
computational methods. The origin of stereoselectivity rendered by this hybrid
bifunctional catalyst in asymmetric protonation is investigated for the first
time using suitable transition-state models. A detailed conformational analysis
of N-[3,5-bis(trifluoromethyl)]phenylthiourea-based epicinchonidine reveals the
potential for a bifunctional mode of activation of the substrate alpha-amino
malonate hemiester through hydrogen bonding. Six different conformer families
differing in characteristic dihedral angles are identified within a range of 16
kcal/mol with respect to the lowest energy conformer. Different likely
mechanistic pathways obtained through detailed analysis of the transition states
and intermediates are compared. It is identified that in the preferred pathway,
the decarboxylation is followed by a direct proton transfer from the chiral
quinuclidinium moiety to the enolate carbon as opposed to a conventional
protonation at the enolate oxygen followed by a keto-enol tautomerization. The
factors responsible for high levels of observed stereoselectivity are traced to
interesting hydrogen-bonding interactions offered by the thiourea-cinchona
bifunctional framework. The predicted stereoselectivities using computed Gibbs
free energies of diastereomeric transition states are in fair agreement with the
experimental stereoselectivities.
PMID- 23153358
TI - The Alberta moving beyond breast cancer (AMBER) cohort study: a prospective study
of physical activity and health-related fitness in breast cancer survivors.
AB - BACKGROUND: Limited research has examined the association between physical
activity, health-related fitness, and disease outcomes in breast cancer
survivors. Here, we present the rationale and design of the Alberta Moving Beyond
Breast Cancer (AMBER) Study, a prospective cohort study designed specifically to
examine the role of physical activity and health-related fitness in breast cancer
survivorship from the time of diagnosis and for the balance of life. The AMBER
Study will examine the role of physical activity and health-related fitness in
facilitating treatment completion, alleviating treatment side effects, hastening
recovery after treatments, improving long term quality of life, and reducing the
risks of disease recurrence, other chronic diseases, and premature death.
METHODS/DESIGN: The AMBER Study will enroll 1500 newly diagnosed, incident, stage
I-IIIc breast cancer survivors in Alberta, Canada over a 5 year period.
Assessments will be made at baseline (within 90 days of surgery), 1 year, and 3
years consisting of objective and self-reported measurements of physical
activity, health-related fitness, blood collection, lymphedema, patient-reported
outcomes, and determinants of physical activity. A final assessment at 5 years
will measure patient-reported data only. The cohort members will be followed for
an additional 5 years for disease outcomes. DISCUSSION: The AMBER cohort will
answer key questions related to physical activity and health-related fitness in
breast cancer survivors including: (1) the independent and interactive
associations of physical activity and health-related fitness with disease
outcomes (e.g., recurrence, breast cancer-specific mortality, overall survival),
treatment completion rates, symptoms and side effects (e.g., pain, lymphedema,
fatigue, neuropathy), quality of life, and psychosocial functioning (e.g.,
anxiety, depression, self-esteem, happiness), (2) the determinants of physical
activity and health-related fitness including demographic, medical, social
cognitive, and environmental variables, (3) the mediators of any observed
associations between physical activity, health-related fitness, and health
outcomes including biological, functional, and psychosocial, and (4) the
moderators of any observed associations including demographic, medical, and
biological/disease factors. Taken together, these data will provide a
comprehensive inquiry into the outcomes, determinants, mechanisms, and moderators
of physical activity and health-related fitness in breast cancer survivors.
PMID- 23153359
TI - Wanted: role models--medical students' perceptions of professionalism.
AB - BACKGROUND: Transformation of medical students to become medical professionals is
a core competency required for physicians in the 21st century. Role modeling was
traditionally the key method of transmitting this skill. Medical schools are
developing medical curricula which are explicit in ensuring students develop the
professional competency and understand the values and attributes of this role.
The purpose of this study was to determine student perception of professionalism
at the University of Ottawa and gain insights for improvement in promotion of
professionalism in undergraduate medical education. METHODS: Survey on student
perception of professionalism in general, the curriculum and learning environment
at the University of Ottawa, and the perception of student behaviors, was
developed by faculty and students and sent electronically to all University of
Ottawa medical students. The survey included both quantitative items including an
adapted Pritzker list and qualitative responses to eight open ended questions on
professionalism at the Faculty of Medicine, University of Ottawa. All analyses
were performed using SAS version 9.1 (SAS Institute Inc. Cary, NC, USA). Chi
square and Fischer's exact test (for cell count less than 5) were used to derive
p-values for categorical variables by level of student learning. RESULTS: The
response rate was 45.6% (255 of 559 students) for all four years of the
curriculum. 63% of the responses were from students in years 1 and 2
(preclerkship). Students identified role modeling as the single most important
aspect of professionalism. The strongest curricular recommendations included
faculty-led case scenario sessions, enhancing interprofessional interactions and
the creation of special awards to staff and students to "celebrate"
professionalism. Current evaluation systems were considered least effective. The
importance of role modeling and information on how to report lapses and breaches
was highlighted in the answers to the open ended questions. CONCLUSIONS: Students
identify the need for strong positive role models in their learning environment,
and for effective evaluation of the professionalism of students and teachers.
Medical school leaders must facilitate development of these components within the
MD education and faculty development programs as well as in clinical milieus
where student learning occurs.
PMID- 23153361
TI - Hydration shell parameters of aqueous alcohols: THz excess absorption and packing
density.
AB - Solvation in water requires minimizing the perturbations in its hydrogen bonded
network. Hence solutes distort water molecular motions in a surrounding domain,
forming a molecule-specific hydration shell. The properties of those hydration
shells impact the structure and function of the solubilized molecules, both at
the single molecule and at higher order levels. The size of the hydration shell
and the picoseconds time-scale water dynamics retardation are revealed by
terahertz (THz) absorption coefficient measurements. Room-temperature absorption
coefficient at f = 0.28 [THz] is measured as a function of alcohol concentration
in aqueous methanol, ethanol, 1,2-propanol, and 1-butanol solutions. Highly
diluted alcohol measurements and enhanced overall measurement accuracy are
achieved with a THz absorption measurement technique of nL-volume liquids in a
capillary tube. In the absorption analysis, bulk and interfacial molecular
domains of water and alcohol are considered. THz ideal and excess absorption
coefficients are defined in accordance with thermodynamics mixing formulations.
The parameter extraction method is developed based on a THz excess absorption
model and hydrated solute molecule packing density representation. First, the
hydration shell size is deduced from the hydrated solute packing densities at two
specific THz excess absorption nonlinearity points: at infinite alcohol dilution
(IAD) and at the THz excess absorption extremum (EAE). Consequently, interfacial
water and alcohol molecular domain absorptions are deduced from the THz excess
absorption model. The hydration shell sizes obtained at the THz excess absorption
extremum are in excellent agreement with other reports. The hydration shells of
methanol, ethanol, 1- and 2-propanol consist of 13.97, 22.94, 22.99, and 31.10
water molecules, respectively. The hydration shell water absorption is on average
0.774 +/- 0.028 times the bulk water absorption. The hydration shell parameters
might shed light on hydration dynamics of biomolecules.
PMID- 23153360
TI - The impact of insecticide-treated school uniforms on dengue infections in school
aged children: study protocol for a randomised controlled trial in Thailand.
AB - BACKGROUND: There is an urgent need to protect children against dengue since this
age group is particularly sensitive to the disease. Since dengue vectors are
active mainly during the day, a potential target for control should be schools
where children spend a considerable amount of their day. School uniforms are the
cultural norm in most developing countries, worn throughout the day. We
hypothesise that insecticide-treated school uniforms will reduce the incidence of
dengue infection in school-aged children. Our objective is to determine the
impact of impregnated school uniforms on dengue incidence. METHODS: A randomised
controlled trial will be conducted in eastern Thailand in a group of schools with
approximately 2,000 students aged 7-18 years. Pre-fabricated school uniforms will
be commercially treated to ensure consistent, high-quality insecticide
impregnation with permethrin. A double-blind, randomised, crossover trial at the
school level will cover two dengue transmission seasons. DISCUSSION: Practical
issues and plans concerning intervention implementation, evaluation, analysing
and interpreting the data, and possible policy implications arising from the
trial are discussed. TRIAL REGISTRATION: clinicaltrial.gov. REGISTRATION NUMBER:
NCT01563640.
PMID- 23153362
TI - Northern = smart and Southern = nice: the development of accent attitudes in the
United States.
AB - Adults evaluate others based on their speech, yet little is known of the
developmental trajectory by which accent attitudes are acquired. Here we
investigate the development of American children's attitudes about Northern- and
Southern-accented American English. Children in Illinois (the "North") and
Tennessee (the "South") evaluated the social desirability, personality
characteristics, and geographic origins of Northern- and Southern-accented
individuals. Five- to 6-year-old children in Illinois preferred the Northern
accented speakers as potential friends, yet did not demonstrate knowledge of any
stereotypes about the different groups; 5-6-year-old children in Tennessee did
not show a preference towards either type of speaker. Nine- to 10-year-old
children in both Illinois and Tennessee evaluated the Northern-accented
individuals as sounding "smarter" and "in charge", and the Southern-accented
individuals as sounding "nicer." Thus, older children endorse similar stereotypes
to those observed in adulthood. These accent attitudes develop in parallel across
children in different regions and reflect both positive and negative assessments
of a child's own group.
PMID- 23153363
TI - Dihydrotestosterone induces SREBP-1 expression and lipogenesis through the
phosphoinositide 3-kinase/Akt pathway in HaCaT cells.
AB - BACKGROUND: The purpose of this study was to investigate the effects and
mechanisms of dihydrotestosterone (DHT)-induced expression of sterol regulatory
element binding protein-1 (SREBP-1), and the synthesis and secretion of lipids,
in HaCaT cells. HaCaT cells were treated with DHT and either the phosphoinositide
3-kinase inhibitor LY294002 or the extracellular-signal-regulated kinase (ERK)
inhibitor PD98059. Real time-PCR, Western blot, Oil Red staining and flow
cytometry were employed to examine the mRNA and protein expressions of SREBP-1,
the gene transcription of lipid synthesis, and lipid secretion in HaCaT cells.
FINDINGS: We found that DHT upregulated mRNA and protein expressions of SREBP-1.
DHT also significantly upregulated the transcription of lipid synthesis-related
genes and increased lipid secretion, which can be inhibited by the addition of
LY294002. CONCLUSIONS: Collectively, these results indicate that DHT induces
SREBP-1 expression and lipogenesis in HaCaT cells via activation of the
phosphoinositide 3-kinase/Akt Pathway.
PMID- 23153364
TI - The complete swine olfactory subgenome: expansion of the olfactory gene
repertoire in the pig genome.
AB - BACKGROUND: Insects and animals can recognize surrounding environments by
detecting thousands of chemical odorants. Olfaction is a complicated process that
begins in the olfactory epithelium with the specific binding of volatile odorant
molecules to dedicated olfactory receptors (ORs). OR proteins are encoded by the
largest gene superfamily in the mammalian genome. RESULTS: We report here the
whole genome analysis of the olfactory receptor genes of S. scrofa using
conserved OR gene specific motifs and known OR protein sequences from diverse
species. We identified 1,301 OR related sequences from the S. scrofa genome
assembly, Sscrofa10.2, including 1,113 functional OR genes and 188 pseudogenes.
OR genes were located in 46 different regions on 16 pig chromosomes. We
classified the ORs into 17 families, three Class I and 14 Class II families, and
further grouped them into 349 subfamilies. We also identified inter- and intra
chromosomal duplications of OR genes residing on 11 chromosomes. A significant
number of pig OR genes (n = 212) showed less than 60% amino acid sequence
similarity to known OR genes of other species. CONCLUSION: As the genome assembly
Sscrofa10.2 covers 99.9% of the pig genome, our analysis represents an almost
complete OR gene repertoire from an individual pig genome. We show that S. scrofa
has one of the largest OR repertoires, suggesting an expansion of OR genes in the
swine genome. A significant number of unique OR genes in the pig genome may
suggest the presence of swine specific olfactory stimulation.
PMID- 23153365
TI - Activation of Rac1-dependent redox signaling is critically involved in
staurosporine-induced neurite outgrowth in PC12 cells.
AB - Staurosporine, a non-specific protein kinase inhibitor, has been shown to induce
neurite outgrowth in PC12 cells, but the mechanism by which staurosporine induces
neurite outgrowth is still obscure. In the present study, we investigated whether
the activation of Rac1 was responsible for the neurite outgrowth triggered by
staurosporine. Staurosporine caused rapid neurite outgrowth independent of the
ERK signaling pathways. In contrast, neurite outgrowth in response to
staurosporine was accompanied by activation of Rac1, and the Rac1 inhibitor
NSC23766 attenuated the staurosporine-induced neurite outgrowth in a
concentration-dependent manner. In addition, suppression of Rac1 activity by
expression of the dominant negative mutant Rac1N17 also blocked the staurosporine
induced morphological differentiation of PC12 cells. Staurosporine caused an
activation of NADPH oxidase and increased the production of reactive oxygen
species (ROS), which was prevented by NSC23766 and diphenyleneiodonium (DPI), an
NADPH oxidase inhibitor. Staurosporine-induced neurite outgrowth was attenuated
by pretreatment with DPI and exogenous addition of sublethal concentration of
H2O2 accelerated neurite outgrowth triggered by staurosporine. These results
indicate that activation of Rac1, which leads to ROS generation, is required for
neurite outgrowth induced by staurosporine in PC12 cells.
PMID- 23153366
TI - Neuroimaging features of C9ORF72 expansion.
AB - Hexanucleotide expansion intronic to chromosome 9 open reading frame 72 (C9ORF72)
has recently been identified as the most common genetic cause of both familial
and sporadic amyotrophic lateral sclerosis and of frontotemporal dementia with or
without concomitant motor neuron disease. Given the common frequency of this
genetic aberration, clinicians seek to identify neuroimaging hallmarks
characteristic of C9ORF72-associated disease, both to provide a better
understanding of the underlying degenerative patterns associated with this
mutation and to enable better identification of patients for genetic screening
and diagnosis. A survey of the literature describing C9ORF72 neuroimaging thus
far suggests that patients with this mutation may demonstrate symmetric frontal
and temporal lobe, insular, and posterior cortical atrophy, although temporal
involvement may be less than that seen in other mutations. Some studies have also
suggested cerebellar and thalamic involvement in C9ORF72-associated disease.
Diffuse cortical atrophy that includes anterior as well as posterior structures
and subcortical involvement thus may represent unique features of C9ORF72.
PMID- 23153367
TI - Free-Wilson and structural approaches to co-optimizing human and rodent isoform
potency for 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitors.
AB - 11beta-Hydroxysteroid dehydrogenase 1 (11beta-HSD1) has been a target of
intensive research efforts across the pharmaceutical industry, due to its
potential for the treatment of type II diabetes and other elements of the
metabolic syndrome. To demonstrate the value of 11beta-HSD1 in preclinical
models, we required inhibitors with good potency against both human and rodent
isoforms. Herein, we describe our efforts to understand how to co-optimize human
and murine potency within the (5-hydroxy-2-adamantyl)-pyrimidine-5-carboxamide
series. Two approaches are described-a data-driven (Free-Wilson) analysis and a
structure-based design approach. The conclusions from these approaches were used
to inform an efficient campaign to design compounds with consistently good
human/murine potency within a logD(7.4) range of 1-3. Compounds 20 and 26
demonstrated good rodent PK, which allowed us to demonstrate a PK/PD relationship
in rat and mouse. We then evaluated 26 against glycemic and body weight end
points in murine disease models, where it demonstrated glucose and body weight
efficacy at 300 mg/kg/day but only body weight efficacy at 50 mg/kg/day, despite
providing >90% target engagement in the liver.
PMID- 23153368
TI - Electrocardiographic P-wave characteristics in patients with psoriasis vulgaris.
AB - PURPOSE: Psoriasis vulgaris is one of the most common skin disorders. Patients
with psoriasis carry an excessive risk of atrial fibrillation (AF). The
differences between the maximum (Pmax) and the minimum (Pmin) P-wave duration on
ECG are defined as P-wave dispersion (PWD). Prolongation of PWD is an independent
risk factor for the development of AF. The aim of this the study was to
investigate P-wave duration and PWD in patients with psoriasis. METHODS: Sixty
one adult patients with psoriasis vulgaris (group 1) and 58 age and sex-matched
healthy individuals (group 2) were included in this study. ECG recordings were
obtained, and the P-wave variables were calculated. Results were reported as mean
+/- standard deviation and percentages. Continuous variables were analysed using
Student's t test. A value of P < 0.05 was considered statistically significant.
RESULTS: Pmax and PWD were significantly higher in group 1 than in group 2 (108.8
+/- 21.3 ms versus 93.3 +/- 13.0 ms, P < 0.001; 67.4 +/- 22.9 ms versus 45.0 +/-
19.6 ms, P < 0.001, respectively). Also, Pmin was significantly lower in group 1
(41.3 +/- 12.3 ms versus 48.3 +/- 14.3 ms, P = 0.04). The psoriasis disease
activity score and hsCRP correlated with PWD (P < 0.01). CONCLUSIONS: Atrial
conduction of sinus impulses was impaired in patients with psoriasis vulgaris. It
was more prominent in patients with severe disease. Physicians caring for
patients with psoriasis vulgaris should screen them for AF development.
PMID- 23153369
TI - The SIDS--critical diaphragm failure hypothesis revisited.
PMID- 23153370
TI - Immobilizing performances, comfort, and user-friendliness of the shoulder
abduction-external rotation braces.
AB - BACKGROUND: Shoulder external rotation braces used for patients with a first-time
shoulder dislocation are designed with a variety of arm positions in abduction as
well as external rotation. However, few studies have focused on their
immobilizing performance, comfort, or user-friendliness. Especially, there have
been no robust data of shoulder abduction-external rotation (A-ER) braces in
comparison to those of external rotation (ER) braces. METHODS: Four types of
commercially available shoulder braces (two ER and two A-ER braces) were tested
in 30 healthy participants. The angles of external rotation and abduction were
measured for each brace at initial application, after simulated daily activities,
and after reapplication. Then, subjects were asked to assess the discomfort of
bracing and difficulty of reapplication using a visual analogue scale. Data were
compared between the two ER braces and two A-ER braces as well as among the four
braces. RESULTS: For both external rotation angle and subjective assessment,
there were no significant differences between the ER and A-ER braces. Among the
four braces, the measurement of arm position demonstrated no significant
differences, except the external rotation angles between the two ER braces. The A
ER braces were assessed to be significantly less comfortable than the ER braces
in the subjective assessment. CONCLUSIONS: Immobilization using the A-ER braces
could maintain the arm position in abduction-external rotation with comparable
user-friendliness, although they tended to be less comfortable during daily
activities compared to the ER braces.
PMID- 23153371
TI - Prevalence and severity of atherosclerosis in extra cranial carotid arteries in
Nigeria: an autopsy study.
AB - BACKGROUND: There has been a paucity of autopsy studies on atherosclerotic
lesions in Nigerians, the last one conducted at our centre being more than four
decades ago. There has also been considerable epidemiological transition. The
objective of the study was to determine the frequency, severity, pattern and
distribution of atherosclerotic lesions in extra cranial carotid arteries (ECCA)
in Nigerians at autopsy. METHODS: ECCA of 30 consecutive Nigerian patients
undergoing autopsy at a University teaching hospital were examined using the
American Heart Association (AHA) histological grading and classification of
atherosclerosis. RESULTS: Atherosclerotic lesions of ECCA were present in 73.3%
of the subjects with the right and the left carotid bifurcations (28.3%) being
the most frequently affected sites. Using the AHA classification of
atherosclerosis, a total of 176(73.3%) lesions were found in the 240 histological
sections of blood vessels examined. Of these, 22.5% were types I, 22.5% were
types II, 15.4% were type V, and 7.5% were type III. The VII to type IX lesions
were rare. When these atherosclerotic lesions were grouped into mild, moderate
and severe, 52.5% were mild lesions (types I-III); 18.3% were moderate lesions
(types IV and V); and 2.5% were severe lesions (types VI to IX). The severe
lesions were most frequently observed in the left carotid bifurcation (50%) and
they first appeared in the age group 45-49 years. Age, hypertension and diabetes
mellitus were strong risk factors for atherosclerosis. CONCLUSIONS: Compared with
four decades ago there has been an apparent increase in severity and extent of
ECCA atherosclerosis especially after the age of 45 years in autopsies from our
centre. This change in the amount of atherosclerosis over time is possibly due to
the epidemiologic transition. This may worsen the rise in stoke incidence within
this community and as such, great effort should be made to follow-up and manage
CVD risk factors within the community.
PMID- 23153372
TI - Formation of iron(III) (hydr)oxides on polyaspartate- and alginate-coated
substrates: effects of coating hydrophilicity and functional group.
AB - To better understand the transport of contaminants in aqueous environments, we
need more accurate information about heterogeneous and homogeneous nucleation of
iron(III) hydroxide nanoparticles in the presence of organics. We combined
synchrotron-based grazing incidence small-angle X-ray scattering (GISAXS) and
SAXS and other nanoparticle and substrate surface characterization techniques to
observe iron(III) (hydr)oxide [10-4 M Fe(NO3)3 in 10 mM NaNO3] precipitation on
quartz and on polyaspartate- and alginate-coated glass substrates and in solution
(pH = 3.7 +/- 0.2). Polyaspartate was determined to be the most negatively
charged substrate and quartz the least; however, after 2 h, total nanoparticle
volume calculations--from GISAXS--indicate that positively charged precipitation
on quartz is twice that of alginate and 10 times higher than on polyaspartate,
implying that electrostatics do not govern iron(III) (hydr)oxide nucleation. On
the basis of contact angle measurements and surface characterization, we
concluded that the degree of hydrophilicity may control heterogeneous nucleation
on quartz and organic-coated substrates. The arrangement of functional groups at
the substrate surface (--OH and --COOH) may also contribute. These results
provide new information for elucidating the effects of polymeric organic
substrate coatings on the size, volume, and location of nucleating iron
hydroxides, which will help predict nanoparticle interactions in natural and
engineered systems.
PMID- 23153373
TI - Microfluidic fabrication and thermoreversible response of core/shell photonic
crystalline microspheres based on deformable nanogels.
AB - Soft photonic crystals (PC) are more appealing due to the responsiveness of the
building blocking-deformable nanoparticles to the external stimuli. In this
report, we demonstrate, for the first time, the generation of soft core/shell PC
microspheres through a combination of a microfluidic technique, encapsulation of
well-ordered temperature responsive polymer nanogels suspension, and
photopolymerization of a transparent shell resin. This strategy not only ensures
the monodispersity of core/shell PC microspheres, but also precisely controls
their size, shell thickness, and optical properties by simply adjusting the flow
rate ratio and mass fraction of the nanogels. More interestingly, the intensity
of the reflection spectra of the crystalline nanogel arrays in the core can be
modulated reversibly by controlling the shell thickness or the temperature. As a
result of their symmetric structure, the resulting PC microspheres exhibited
excellent structural colors and photonic band gaps for normal incident light
independent of the position on the spherical surface. Multifunctional PC
microspheres can also be generated by simply dispersing functional species
together with the nanogels. This core/shell PC microsphere with tunable shell
thickness and reversible thermoresponse could be significant for potential
applications in the fields of chemical/biological sensors, display, encoding, and
optical switching.
PMID- 23153374
TI - Graphene/single-walled carbon nanotube hybrids: one-step catalytic growth and
applications for high-rate Li-S batteries.
AB - The theoretically proposed graphene/single-walled carbon nanotube (G/SWCNT)
hybrids by placing SWCNTs among graphene planes through covalent C-C bonding are
expected to have extraordinary physical properties and promising engineering
applications. However, the G/CNT hybrids that have been fabricated differ greatly
from the proposed G/SWCNT hybrids because either the covalent C-C bonding is not
well constructed or only multiwalled CNTs/carbon nanofibers rather than SWCNTs
are available in the hybrids. Herein, a novel G/SWCNT hybrid was successfully
fabricated by a facile catalytic growth on layered double hydroxide (LDH) at a
high temperature over 950 degrees C. The thermally stable Fe nanoparticles and
the uniform structure of the calcined LDH flakes are essential for the
simultaneously catalytic deposition of SWCNTs and graphene. The SWCNTs and the
CVD-grown graphene, as well as the robust connection between the SWCNTs and
graphene, facilitated the construction of a high electrical conductive pathway.
The internal spaces between the two stacked graphene layers and among SWCNTs
offer room for sulfur storage. Therefore, the as obtained G/SWCNT-S cathode
exhibited excellent performance in Li-S batteries with a capacity as high as 650
mAh g(-1) after 100 cycles even at a high current rate of 5 C. Such a novel
G/SWCNT hybrid can serve not only as a prototype to shed light on the chemical
principle of G/CNT synthesis but also as a platform for their further
applications in the area of nanocomposites, heterogeneous catalysis, drug
delivery, electrochemical energy storage, and so on.
PMID- 23153375
TI - The reconstruction of two large full-thickness wounds of the upper lip with
different operative techniques: when possible, a local flap repair is preferable
to reconstruction with free tissue transfer.
AB - BACKGROUND: Large full-thickness wounds of the upper lip are often referred to
operating room-based surgeons for repair given the perceived difficulties in
restoring upper lip form and function with simpler operative techniques.
OBJECTIVE: To illustrate the functional, aesthetic, and cost differences between
two techniques used to repair full-thickness wounds of the upper lip. MATERIALS
AND METHODS: Two patients with difficult full-thickness wounds of the majority of
the upper lip were reviewed. One patient underwent reconstruction with a
composite free flap in an operating room, and one underwent repair using local
tissue rearrangement using bilateral modified nasolabial flaps in an outpatient
setting. RESULTS: Both patients were adequately reconstructed, but the patient
repaired using local tissue rearrangement had a better aesthetic outcome and
superior preservation of oral competency. In addition, the costs of this
patient's reconstructive care were less than 2.4% of the costs of the care of the
patient repaired using a free flap. CONCLUSION: When possible, large, full
thickness wounds of the upper lip should be repaired with local tissue
rearrangement in an outpatient setting to offer patients potential improvements
in functional and aesthetic outcomes while minimizing treatment costs.
PMID- 23153376
TI - Duplex destabilization by four ribosomal DEAD-box proteins.
AB - DEAD-box proteins are believed to participate in the folding of RNA by
destabilizing RNA secondary or tertiary structures. Although these proteins bind
and hydrolyze ATP, the mechanism by which nucleotide hydrolysis is coupled to
helix destabilization may vary among different DEAD-box proteins. To investigate
their abilities to disrupt helices and couple ATP hydrolysis to unwinding, we
assayed the Saccharomyces cerevisiae ribosomal DEAD-box proteins, Dbp3p, Dbp4p,
Rok1p, and Rrp3p utilizing a series of RNA substrates containing a short duplex
and either a 5' or 3' single-stranded region. All four proteins unwound a 10 bp
helix in vitro in the presence of ATP; however, significant dissociation of
longer helices was not observed. While Dbp3p did not require a single-stranded
extension to disrupt a helix, the unwinding activities of Dbp4p, Rok1p, and Rrp3p
were substantially stimulated by either a 5' or 3' single-stranded extension.
Interestingly, these proteins showed a clear length dependency with 3' extensions
that was not observed with 5' extensions, suggesting that they bind substrates
with a preferred orientation. In the presence of AMPPNP or ADP, all four proteins
displayed displacement activity suggesting that nucleotide binding is sufficient
to facilitate duplex disruption. Further enhancement of the strand displacement
rate in the presence of ATP was observed for only Dbp3p and Rrp3p.
PMID- 23153377
TI - Pyrethroid pesticide exposure and risk of childhood acute lymphocytic leukemia in
Shanghai.
AB - Significant amounts of pyrethroid pesticides are used throughout China. Previous
studies have suggested that exposure to pesticides may increase the risk of
childhood cancer; however, few studies have focused on pyrethroid metabolites. We
investigated five nonspecific metabolites of pyrethroid pesticides found in
children's urine and examined the correlation with childhood leukemia. We
conducted a hospital-based case-control study of childhood acute lymphocytic
leukemia (ALL) in Shanghai between 2010 and 2011. The study included 176 children
aged 0-14 years and 180 controls matched for age and sex. Compared with those in
the lowest quartiles of total and individual metabolites, the highest quartiles
were associated with an approximate 2-fold increased risk of ALL [total
metabolites: odds ratio (OR) = 2.75, 95% confidence interval (CI), 1.43-5.29; cis
DCCA: OR = 2.21, 95% CI, 1.16-4.19; trans-DCCA: OR = 2.33, 95% CI, 1.23-4.41; and
3-PBA: OR = 1.84, 95% CI, 1.00-3.38], and most of the positive trends were
significant (p < 0.05). Our findings suggest that urinary levels of pyrethroid
metabolites may be associated with an elevated risk of childhood ALL and
represent a previously unreported quantitative exposure assessment for childhood
leukemia.
PMID- 23153378
TI - Comparing P300 modulations: target-to-target interval versus infrequent nontarget
to-nontarget interval in a three-stimulus task.
AB - This study examined temporal determinants of the P300 component of the ERP in a
three-stimulus visual oddball task. Frequent standards, with equiprobable targets
and infrequent nontargets, were utilized. We tested whether the infrequent
nontarget-to-nontarget interval (infrequent NNI) influences P300 amplitudes and
latencies analogously to the target-to-target interval (TTI). EEG was recorded
from 27 participants, and response time and P300 effects of TTIs and infrequent
NNIs were assessed. Increases in TTI augmented target P300 amplitudes and
decreased latencies and response times. However, this modulation of P300
amplitude was weak for manipulations of infrequent NNI. P300 latencies increased
initially before decreasing across infrequent NNI levels. Together, these
findings support the notion that the P300 has an underlying temporal mechanism
that is modulated by motivationally significant events. Theoretical implications
are discussed.
PMID- 23153379
TI - Benefits of hyperthermic intraperitoneal chemotherapy for patients with serosal
invasion in gastric cancer: a meta-analysis of the randomized controlled trials.
AB - BACKGROUND: In this meta-analysis we aimed to determine the effectiveness and
safety of hyperthermic intraperitoneal chemotherapy (HIPC) for patients with
advanced gastric cancer who underwent gastrectomy. METHODS: In accordance with
standard meta-analysis procedures, our study included patients who underwent
resection for advanced gastric cancer and were randomly allocated to receive
either hyperthermic intraperitoneal chemotherapy or control. We searched PubMed
(up to November 2011), EMBASE (up to November 2011), Cochrane Database of
Systematic Reviews (CDSR), and Cochrane Central Register of Controlled Trials
(CCTR) (up to November 2011). Both published and unpublished trials were included
in the analysis, and no search restrictions were imposed. There was no language
restriction. The results were analyzed using RevMan 5.1 software, which was
provided by Cochrane Collaboration. RESULTS: There were ten randomized controlled
trials included in the analysis. A total of 1062 patients with gastric cancer in
these studies were divided into the HIPC group (n = 518) and control group (n =
544). A significant improvement in survival was observed in the HIPC groups
compared to the control group in the mitomycin C (MMC) subgroup (RR = 0.75, 95%CI
0.65-0.86; P < 0.00001) and the 5-FU group (RR = 0.69, 95%CI 0.52-0.90; P <
0.00001); the total RR was 0.73 (95%CI 0.64-0.83; P < 0.00001). Our findings
indicated that HIPC potentially exhibited a lower peritoneal recurrence rate in
the HIPC group compared to the control group (RR = 0.45, 95%CI 0.28-0.72; P =
0.001). CONCLUSIONS: Our meta-analysis demonstrated that HIPC may improve the
overall survival rate for patients who receive resection for advance gastric
cancer potentially, and help to prevent peritoneal local recurrence among
patients with serosal invasion in gastric cancer.
PMID- 23153380
TI - Temporal aggregation impacts on epidemiological simulations employing
microcontact data.
AB - BACKGROUND: Microcontact datasets gathered automatically by electronic devices
have the potential augment the study of the spread of contagious disease by
providing detailed representations of the study population's contact dynamics.
However, the impact of data collection experimental design on the subsequent
simulation studies has not been adequately addressed. In particular, the impact
of study duration and contact dynamics data aggregation on the ultimate outcome
of epidemiological models has not been studied in detail, leaving the potential
for erroneous conclusions to be made based on simulation outcomes. METHODS: We
employ a previously published data set covering 36 participants for 92 days and a
previously published agent-based H1N1 infection model to analyze the impact of
contact dynamics representation on the simulated outcome of H1N1 transmission. We
compared simulated attack rates resulting from the empirically recorded contact
dynamics (ground truth), aggregated, typical day, and artificially generated
synthetic networks. RESULTS: No aggregation or sampling policy tested was able to
reliably reproduce results from the ground-truth full dynamic network. For the
population under study, typical day experimental designs - which extrapolate from
data collected over a brief period - exhibited too high a variance to produce
consistent results. Aggregated data representations systematically overestimated
disease burden, and synthetic networks only reproduced the ground truth case when
fitting errors systemically underestimated the total contact, compensating for
the systemic overestimation from aggregation. CONCLUSIONS: The
interdepedendencies of contact dynamics and disease transmission require that
detailed contact dynamics data be employed to secure high fidelity in simulation
outcomes of disease burden in at least some populations. This finding serves as
motivation for larger, longer and more socially diverse contact dynamics tracing
experiments and as a caution to researchers employing calibrated aggregate
synthetic representations of contact dynamics in simulation, as the calibration
may underestimate disease parameters to compensate for the overestimation of
disease burden imposed by the aggregate contact network representation.
PMID- 23153381
TI - Synthesis of a potent antimalarial amphilectene.
AB - 7-Isocyano-11(20),14-epiamphilectadiene, the most potent of antimalarial
amphilectenes, is synthesized in seven steps from readily available materials.
The synthesis is enabled by a new dendrimeric triene (Danishefsky [3]-dendralene)
and a new method for stereo- and chemoselective isocyanation. This chemistry
provides a useful entry into an underexplored yet promising family of
antimalarial terpenoids.
PMID- 23153382
TI - Efficacy of single-session abreactive ego state therapy for combat stress injury,
PTSD, and ASD.
AB - Using abreactive Ego State Therapy (EST), 36 patients meeting DSM-IV-TR and PTSD
checklist (PCL) criteria were exposed to either 5-6 hours of manualized treatment
or placebo in a single session. EST emphasizes repeated hypnotically activated
abreactive "reliving" of the trauma experience combined with therapists' ego
strength. Both the placebo and EST treatment groups showed significant reductions
in PTSD checklist scores immediately posttreatment (placebo: mean 17.34 points;
EST: mean 53.11 points) but only the EST patients maintained significant
treatment effect at 4-week and 16- to 18-week follow-ups. Abreactive EST appears
to be an effective and durable treatment for PTSD inclusive of combat stress
injury and acute stress disorder.
PMID- 23153383
TI - Efficacy of abreactive ego state therapy for PTSD: trauma resolution, depression,
and anxiety.
AB - Using manualized abreactive Ego State Therapy (EST), 30 subjects meeting DSM-IV
TR and Clinician-Administered PTSD Scale (CAPS) criteria were exposed to either 5
6 hours of treatment or the Ochberg Counting Method (placebo) in a single
session. EST emphasized repeated hypnotically activated abreactive "reliving" of
the trauma and ego strengthening by the cotherapists. Posttreatment 1-month and 3
month follow-ups showed EST to be an effective treatment for PTSD. Using the
Davidson Trauma Scale, Beck Depression II, and Beck Anxiety Scales, EST subjects
showed significant positive effects from pretreatment levels at all posttreatment
measurement periods in contrast to the placebo treatment. Most of the EST
subjects responded and showed further improvement over time.
PMID- 23153384
TI - Group hypnotherapy for irritable bowel syndrome with long-term follow-up.
AB - This study tested whether group gut-focused hypnotherapy would improve irritable
bowel syndrome (IBS). Several possible outcome predictors were also studied.
Before treatment, 75 patients completed a Symptom Severity Scale, a Mind-Body
attribution questionnaire, and a Quality of Relationship Inventory (QRI). The
symptom scale was completed posttreatment, 3, 6, and 12 months later. There was
significant symptom reduction at each data point (p < .001). Sixty percent had a
reduction of more than 50 points, indicative of clinical improvement. Initial
severity score (p = .0004) and QRI conflict (p = .057) were directly correlated
with a response to hypnotherapy, while attribution of symptoms to mind
(emotional) causation was inversely correlated (p = .0056). The authors conclude
that group hypnotherapy is effective in patients with IBS.
PMID- 23153385
TI - Flexibility in processing visual information: effects of mood and hypnosis.
AB - This quasi-experiment using a real/simulator model investigated differences in
cognitive flexibility in high and low hypnotizable participants. Using the
variables of hypnotizability (low/high), consciousness
(nonhypnotized/hypnotized), mood (happy/sad), and visual-information processing
(global/local), reaction times and target detection paradigms of the subjects
were evaluated during both nonhypnotic and hypnotic states. Flexibility in
cognitive processing was operationalized as the ability to overcome the typical
global precedence and answer quickly about the nonprevalent local features. It
was observed that the low hypnotizable participants were not influenced in their
preference for the global or local dimension by any manipulated variable, whereas
the high hypnotizables were more flexible.
PMID- 23153386
TI - What motivates professionals to learn and use hypnosis in clinical practice?
AB - The authors devised and validated a questionnaire assessing the various possible
motivations for learning and using hypnosis and administered it to 125 Israeli
psychologists, physicians, and dentists who study and/or use hypnosis in their
clinical work. The results suggest that most professionals were motivated by a
desire to improve their professional performance and that a majority of
professionals were primarily influenced in their desire to learn hypnosis by
colleagues in academically or clinically oriented settings.
PMID- 23153387
TI - A cross-validation of two differing measures of hypnotic depth.
AB - Several sets of regression analyses were completed, attempting to predict 2
measures of hypnotic depth: the self-reported hypnotic depth score and hypnoidal
state score from variables of the Phenomenology of Consciousness Inventory:
Hypnotic Assessment Procedure (PCI-HAP). When attempting to predict self-reported
hypnotic depth, an R of .78 with Study 1 participants shrank to an r of .72 with
Study 2 participants, suggesting mild shrinkage for this more attributional
measure of hypnotic depth. Attempting to predict hypnoidal state (an estimate of
trance) using the same procedure, yielded an R of .56, that upon cross-validation
shrank to an r of .48. These and other results suggest that, although there is
some variance in common, the self-reported hypnotic depth score appears to be
tapping a different construct from the hypnoidal state score.
PMID- 23153388
TI - Hypnosis for management of fibromyalgia.
AB - This randomized, controlled trial contrasted the effects of 5 not-standardized
sessions of hypnosis over 2 months in 59 women with fibromyalgia who were
randomly assigned to treatment (n = 30) or a wait-list control group (n = 29).
Patients in the treated group were encouraged to practice self-hypnosis.
Fibromyalgia Impact Questionnaire (FIQ), MOS-Sleep Scale, Multidimensional
Fatigue Inventory (MFI), Cognitive Strategy Questionnaire (CSQ), and Patient
Global Impression of Change (PGIC) were administered at baseline, 3 months (M3),
and 6 months (M6) after inclusion. Compared to the control, the hypnosis group
reported better improvement on PGIC (p = .001 at M3, p = .01 at M6) and a
significant improvement in sleep and CSQ dramatization subscale (both at M6).
PMID- 23153389
TI - Imageability, age of acquisition, and frequency factors in acronym comprehension.
AB - In spite of their unusual orthographic and phonological form, acronyms (e.g.,
BBC, HIV, NATO) can become familiar to the reader, and their meaning can be
accessed well enough that they are understood. The factors in semantic access for
acronym stimuli were assessed using a word association task. Two analyses
examined the time taken to generate a word association response to acronym cues.
Responses were recorded more quickly to cues that elicited a large proportion of
semantic responses, and those that were high in associative strength.
Participants were shown to be faster to respond to cues which were imageable or
early acquired. Frequency was not a significant predictor of word association
responses. Implications for theories of lexical organisation are discussed.
PMID- 23153390
TI - Sjogren's syndrome-associated oxidative stress and mitochondrial dysfunction:
prospects for chemoprevention trials.
AB - An involvement of oxidative stress (OS) was found in recent studies of Sjogren's
syndrome (SS) that reported significant changes in protein oxidation,
myeloperoxidase activity, TNF-alpha, nitrotyrosine, and GSH levels in plasma from
SS patients. Excess levels of OS markers, as oxidative DNA damage and propanoyl
lysine, were reported in saliva from SS patients. Previous reports concurred with
a role of OS in SS pathogenesis, by showing a decreased expression of antioxidant
activities in conjunctival epithelial cells of SS patients and in parotid gland
tissue samples from SS patients. A link between OS and mitochondrial dysfunction
(MDF) is recognized both on the grounds of the established role of mitochondria
in reactive oxygen species (ROS) formation and by the occurrence of MDF in a set
of OS-related disorders. Earlier studies detected mitochondrial alterations in
cells from SS patients, related to the action of antimitochondrial
autoantibodies, and affecting specific mitochondrial activities. Thus, a link
between MDF and OS may be postulated in SS, prompting studies aimed at
elucidating SS pathogenesis and in the prospect of chemoprevention trials in SS
clinical management.
PMID- 23153391
TI - Cloning and characterization of A cDNA encoding prohibitin1 from Lampetra
japonica and its expression analysis.
AB - To investigate that prohibitin is probably concerned in B--lymphocyte--like cells
mediated signal pathways in Lamprey, a necessary and fundamental plan is firstly
conducted. A full--length cDNA encoding the prohibitin1 protein was cloned from
Lampetra japonica by EST sequence analysis in L. japonica leukocyte cDNA library
conducted by our laboratory. Prohibitin1 contains a 828 bp open reading frame,
encoded 275 amino acids residues, and molecular weight is 29.9517 KD, isoelectric
point is 6.93, consists of 31 negatively charged amino acids residues (Asp+Glu)
and 21 positively charged ones (Arg+Lys). The Prohibitin1 gene sequence from L.
japonica is 71% identical to the ones of other 24 eukaryotic species, which shows
the putative prohibitin1 gene is highly conserved. Western blotting analysis
results showed the recombinant proteins were the target proteins in prokaryote.
Real--time quantitative polymerase chain reaction analysis indicated that the
expression of the prohibitin1 gene is significantly up--regulated in leukocyte,
heart and gill of L. japonica by LPS stress treatment. In conclusion, we have
cloned and identified the full--length cDNA of Prohibitin1 in L. japonica and
found that it was related to adaptive immune response in lamprey for the first
time.
PMID- 23153392
TI - Migratory gene expression signature predicts poor patient outcome: are cancer
stem cells to blame?
AB - Breast cancer metastasis accounts for the majority of deaths from this disease.
In the previous issue of Breast Cancer Research, Patsialou and colleagues used a
novel in vivo invasion assay to capture migrating breast cancer cells and
demonstrate that the gene expression signature of these cells predicts breast
cancer metastasis in a large cohort of patients. Furthermore, specific genes
identified play a functional role in the invasion of MDA-MB-231 breast cancer
cells and in patient-derived breast tumors. These genes regulate pathways known
to be induced in invasion and metastases and play an important role in the
regulation of cancer stem cells.
PMID- 23153393
TI - High-resolution autosomal radiation hybrid maps of the pig genome and their
contribution to the genome sequence assembly.
AB - BACKGROUND: The release of the porcine genome sequence offers great perspectives
for Pig genetics and genomics, and more generally will contribute to the
understanding of mammalian genome biology and evolution. The process of producing
a complete genome sequence of high quality, while facilitated by high-throughput
sequencing technologies, remains a difficult task. The porcine genome was
sequenced using a combination of a hierarchical shotgun strategy and data
generated with whole genome shotgun. In addition to the BAC contig map used for
the clone-by-clone approach, genomic mapping resources for the pig include two
radiation hybrid (RH) panels at two different resolutions. These two panels have
been used extensively for the physical mapping of pig genes and markers prior to
the availability of the pig genome sequence. RESULTS: In order to contribute to
the assembly of the pig genome, we genotyped the two radiation hybrid (RH) panels
with a SNP array (the Illumina porcineSNP60 array) and produced high density
physical RH maps for each pig autosome. We first present the methods developed to
obtain high density RH maps with 38,379 SNPs from the SNP array genotyping. We
then show how they were useful to identify problems in a draft of the pig genome
assembly, and how the RH maps enabled the problems to be corrected in the porcine
genome sequence. Finally, we used the RH maps to predict the position of 2,703
SNPs and 1,328 scaffolds currently unplaced on the porcine genome assembly.
CONCLUSIONS: A complete process, from genotyping of a high density SNP array on
RH panels, to the construction of genome-wide high density RH maps, and finally
their exploitation for validating and improving a genome assembly is presented
here. The study includes the cross-validation of RH based findings with
independent information from genetic data and comparative mapping with the Human
genome. Several additional resources are also provided, in particular the
predicted genomic location of currently unplaced SNPs and associated scaffolds
summing up to a total of 72 megabases, that can be useful for the exploitation of
the pig genome assembly.
PMID- 23153394
TI - Composition of fatty acids in the maternal and umbilical cord plasma of
adolescent and adult mothers: relationship with anthropometric parameters of
newborn.
AB - BACKGROUND: Considering the importance of long chain polyunsaturated fatty acids
to fetal development and the lack of studies that have compared the status of
fatty acids between adolescents and adults mothers, the purpose of this study was
to evaluate the composition of fatty acids in maternal and umbilical cord plasma
from adolescent and adults mothers. METHODS: Forty pregnant adolescents and forty
pregnant adults were selected to assess the distribution profile of fatty acids
in the maternal and umbilical cord plasma. Quantification of fatty acids in the
total lipids of the sample groups was performed through the use of gas-liquid
chromatography. RESULTS: The maternal and umbilical cord plasma of the
adolescents showed a greater concentration of AA than did that of the adults (P <
0.05). However, a greater percentage of EPA was found in the umbilical cord
plasma of the adults (P < 0.05). DHA in the plasma of the adolescent mothers
correlated positively to birth weight and head circumference. CONCLUSIONS: This
suggests that in situations of greater nutritional risk, as in adolescent
pregnancy, n-3PUFA concentrations have a greater influence on the proper
development of newborns. Moreover, variations in fatty acid concentrations in the
maternal and cord plasma of adolescents and adults may indicate that pregnancy
affects the LC-PUFA status of adults and adolescents in distinct ways.
PMID- 23153395
TI - The Uganda Newborn Study (UNEST): an effectiveness study on improving newborn
health and survival in rural Uganda through a community-based intervention linked
to health facilities - study protocol for a cluster randomized controlled trial.
AB - BACKGROUND: Reducing neonatal-related deaths is one of the major bottlenecks to
achieving Millennium Development Goal 4. Studies in Asia and South America have
shown that neonatal mortality can be reduced through community-based
interventions, but these have not been adapted to scalable intervention packages
for sub-Saharan Africa where the culture, health system and policy environment is
different. In Uganda, health outcomes are poor for both mothers and newborn
babies. Policy opportunities for neonatal health include the new national Health
Sector Strategic Plan, which now prioritizes newborn health including use of a
community model through Village Health Teams (VHT). The aim of the present study
is to adapt, develop and cost an integrated maternal-newborn care package that
links community and facility care, and to evaluate its effect on maternal and
neonatal practices in order to inform policy and scale-up in Uganda.
METHODS/DESIGN: Through formative research around evidence-based practices, and
dialogue with policy and technical advisers, we constructed a home-based neonatal
care package implemented by the responsible VHT member, effectively a Community
Health Worker (CHW). This CHW was trained to identify pregnant women and make
five home visits - two before and three just after birth - so that linkages will
be made to facility care and targeted messages for home-care and care-seeking
delivered. The project is improving care in health units to provide standardized
care for the mother and the newborn in both intervention and comparison areas.The
study is taking place in a new Demographic Surveillance Site in two rural
districts, Iganga and Mayuge, in Uganda. It is a two-arm cluster randomized
controlled design with 31 intervention and 32 control areas (villages). The
comparison parishes receive the standard care already being provided by the
district, but to the intervention villages are added a system for CHWs to visit
the mother five times in her home during pregnancy and the neonatal period. Both
areas benefit from a standardized strengthening of facility care for mothers and
neonates. DISCUSSION: UNEST is designed to directly feed into the
operationalization of maternal and newborn care in the national VHT strategy,
thereby helping to inform scale-up in rural Uganda. The study is registered as a
randomized controlled trial, number ISRCTN50321130.
PMID- 23153396
TI - Ultraviolet disinfection of antibiotic resistant bacteria and their antibiotic
resistance genes in water and wastewater.
AB - Disinfection of wastewater treatment plant effluent may be an important barrier
for limiting the spread of antibiotic-resistant bacteria (ARBs) and antibiotic
resistance genes (ARGs). While ideally disinfection should destroy ARGs, to
prevent horizontal gene transfer to downstream bacteria, little is known about
the effect of conventional water disinfection technologies on ARGs. This study
examined the potential of UV disinfection to damage four ARGs, mec(A), van(A),
tet(A), and amp(C), both in extracellular form and present within a host ARBs:
methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant
Enterococcus faecium (VRE), Escherichia coli SMS-3-5, and Pseudomonas aeruginosa
01, respectively. An extended amplicon-length quantitative polymerase chain
reaction assay was developed to enhance capture of ARG damage events and also to
normalize to an equivalent length of target DNA (~1000 bp) for comparison. It was
found that the two Gram-positive ARBs (MRSA and VRE) were more resistant to UV
disinfection than the two Gram-negative ARBs (E. coli and P. aeruginosa). The two
Gram-positive organisms also possessed smaller total genome sizes, which could
also have reduced their susceptibility to UV because of fewer potential
pyrimidine dimer targets. An effect of cell type on damage to ARGs was only
observed in VRE and P. aeruginosa, the latter potentially because of
extracellular polymeric substances. In general, damage of ARGs required much
greater UV doses (200-400 mJ/cm2 for 3- to 4-log reduction) than ARB inactivation
(10-20 mJ/cm2 for 4- to 5-log reduction). The proportion of amplifiable ARGs
following UV treatment exhibited a strong negative correlation with the number of
adjacent thymines (Pearson r < -0.9; p < 0.0001). ARBs surviving UV treatment
were negatively correlated with total genome size (Pearson r < -0.9; p < 0.0001)
and adjacent cytosines (Pearson r < -0.88; p < 0.0001) but positively correlated
with adjacent thymines (Pearson r > 0.85; p < 0.0001). This suggests that
formation of thymine dimers is not the sole mechanism of ARB inactivation.
Overall, the results indicate that UV is limited in its potential to damage ARGs
and other disinfection technologies should be explored.
PMID- 23153397
TI - Terpecurcumins A-I from the rhizomes of Curcuma longa: absolute configuration and
cytotoxic activity.
AB - Terpecurcumins A-I (1-9), together with three known analogues (10-12), were
isolated from the rhizomes of Curcuma longa (turmeric). They were derived from
the hybridization of curcuminoids and bisabolanes. The structures and absolute
configurations of 1-9 were elucidated on the basis of extensive spectroscopic
data analysis, including NMR and electronic circular dichroism spectra. The
configuration of 10 was further confirmed by X-ray crystallography. A plausible
biogenetic relationship for 1-12 is proposed. Compounds 4, 6, 7, 10, and 11
showed higher cytotoxic activities (IC(50), 10.3-19.4 MUM) than curcumin (IC(50),
31.3-49.2 MUM) against human cancer cell lines (A549, HepG2, and MDA-MB-231).
PMID- 23153398
TI - Laparoscopic umbilical hernia repair is the preferred approach in obese patients.
AB - INTRODUCTION: The optimal method of umbilical hernia repair (UHR) in the obese
population, laparoscopic vs open, is not standardized. The purpose of this study
was to determine the optimal surgical option for UHR in the obese population.
METHODS: A retrospective chart review was conducted on 123 obese patients (body
mass index [BMI] >30) who underwent UHR from 2003 to 2009 at a single
institution. Patients were grouped by surgical approach (open vs laparoscopic).
Intraoperative and postoperative courses were compared. Follow-up in the
postoperative period was obtained from patient records and telephone interviews.
RESULTS: Of the 123 patients undergoing UHR, 40 and 83 patients were operated on
with the laparoscopic and open approach, respectively. Patients were well matched
by demographics as well as comorbidities. No difference in the mean BMI was shown
between the laparoscopic and open groups (37 vs 35, P = not significant,
respectively). The operative time was significantly prolonged in the laparoscopic
group (106 vs 71 minutes, P < .01). Intraoperatively, no complications occurred
in either group. In the immediate postoperative period, 1 patient who underwent
laparoscopic UHR was readmitted for small bowel obstruction, and 2 patients in
the open group were readmitted, 1 for pain control and 1 for wound infection.
Follow-up was achieved in 63% of the laparoscopic group and 58% of the open group
with a mean follow-up of 15 months in the laparoscopic group and 20 months in the
open group (P = not significant). A significant increase in wound infection was
reported in the open group with mesh insertion when compared with the
laparoscopic procedure (26% vs 4%, P < .05, respectively). No hernia recurrence
was shown in the laparoscopic vs the open group with mesh insertion (0% vs 4%, P
= not significant, respectively). CONCLUSIONS: In obese patients, the
laparoscopic approach was associated with a significantly lower rate of
postoperative infection and no hernia recurrence. Laparoscopic hernia repair may
be the preferred option in the obese patient.
PMID- 23153399
TI - Total synthesis of (-)-isatisine A.
AB - A modular total synthesis of (-)-isatisine A is described in which four
consecutive metal-mediated transformations have been employed at the final stage.
These include [Pd]-catalyzed Sonogashira coupling, [Pd]-catalyzed nitroalkyne
cycloisomerization leading to isatogens, and addition of indoles to isatogens
using InCl(3)- and [Rh]-catalyzed oxidative N-heterocyclization of amino alcohol
to form the key amide bond. In addition to these, the removal of the protecting
groups has also been carried out in a selective fashion employing either
catalytic or stoichiometric metal/metal-based reagents.
PMID- 23153400
TI - Challenging age-old ideas about stroke.
PMID- 23153401
TI - Traumatic brain injury and neuropsychiatric outcomes.
PMID- 23153402
TI - Sham neurosurgical procedures: the patients' perspective.
PMID- 23153403
TI - West Nile virus bites back.
PMID- 23153404
TI - Andres Kanner: shining light on the behavioural aspects of epilepsy.
PMID- 23153406
TI - Antithrombotic therapy for stroke prevention in non-valvular atrial fibrillation.
AB - The world faces an epidemic of atrial fibrillation and atrial fibrillation
related stroke. An individual's risk of atrial fibrillation-related stroke can be
estimated with the CHADS(2) or CHA(2)DS(2)VASc scores, and reduced by two-thirds
with effective anticoagulation. Vitamin K antagonists, such as warfarin, are
underused and often poorly managed. The direct thrombin inhibitor dabigatran
etexilate and factor Xa inhibitors rivaroxaban and apixaban are new oral
anticoagulants that are at least as efficacious and safe as warfarin. Their
advantages are predictable anticoagulant effects, low propensity for drug
interactions, and lower rates of intracranial haemorrhage than with warfarin. A
disadvantage is the continuing need to develop and validate rapidly effective
antidotes for major bleeding and standardised tests that accurately measure
plasma concentrations and anticoagulant effects, together with the disadvantage
of possible higher rates of gastrointestinal haemorrhage and greater expense than
with warfarin. The new oral anticoagulants should increase the number of patients
with atrial fibrillation at risk of stroke who are optimally anticoagulated, and
reduce the burden of atrial fibrillation-related stroke.
PMID- 23153407
TI - Measurement and clinical effect of grey matter pathology in multiple sclerosis.
AB - During the past 10 years, the intense involvement of the grey matter of the CNS
in the pathology of multiple sclerosis has become evident. On gross inspection,
demyelination in the grey matter is rather inconspicuous, and lesions in the grey
matter are mostly undetectable with traditional MRI sequences. However, the
results of immunohistochemical studies have shown extensive involvement of grey
matter, and researchers have developed and applied new MRI acquisition methods as
a result. Imaging techniques specifically developed to visualise grey matter
lesions indicate early involvement, and image analysis techniques designed to
measure the volume of grey matter show progressive loss. Together, these
techniques have shown that grey matter pathology is associated with neurological
and neuropsychological disability, and the strength of this association exceeds
that related to white matter lesions or whole brain atrophy. By focusing on the
latest insights into the in-vivo measurement of grey matter lesions and atrophy,
we can assess their clinical effects.
PMID- 23153408
TI - Cognitive decline in older adults with a history of traumatic brain injury.
AB - Traumatic brain injury (TBI) is an important public health problem with
potentially serious long-term neurobehavioural sequelae. There is evidence to
suggest that a history of TBI can increase a person's risk of developing
Alzheimer's disease. However, individuals with dementia do not usually have a
history of TBI, and survivors of TBI do not invariably acquire dementia later in
life. Instead, a history of traumatic brain injury, combined with brain changes
associated with normal ageing, might lead to exacerbated cognitive decline in
older adults. Strategies to increase or maintain cognitive reserve might help to
prevent exacerbated decline after TBI. Systematic clinical assessment could help
to differentiate between exacerbated cognitive decline and mild cognitive
impairment, a precursor of Alzheimer's disease, with important implications for
patients and their families.
PMID- 23153409
TI - Autonomous movement of controllable assembled Janus capsule motors.
AB - We demonstrate the first example of a self-propelled Janus polyelectrolyte
multilayer hollow capsule that can serve as both autonomous motor and smart
cargo. This new autonomous Janus capsule motor composed of partially coated
dendritic platinum nanoparticles (Pt NPs) was fabricated by using a template
assisted layer-by-layer (LbL) self-assembly combined with a microcontact printing
method. The resulting Janus capsule motors still retain outstanding delivery
capacities and can respond to external stimuli for controllable encapsulation and
triggered release of model drugs. The Pt NPs on the one side of the Janus capsule
motors catalytically decompose hydrogen peroxide fuel, generating oxygen bubbles
which then recoil the movement of the capsule motors in solution or at an
interface. They could autonomously move at a maximum speed of above 1 mm/s (over
125 body lengths/s), while exerting large forces exceeding 75 pN. Also, these
asymmetric hollow capsules can be controlled by an external magnetic field to
achieve directed movement. This LbL-assembled Janus capsule motor system has
potential in making smart self-propelling delivery systems.
PMID- 23153410
TI - Clinical impact of unsolicited post-prescription antibiotic review in surgical
and medical wards: a randomized controlled trial.
AB - This study aimed to determine the clinical course of patients and the quality of
antibiotic use using a systematic and unsolicited post-prescription antibiotic
review. Seven hundred and fifty-three adult patients receiving antibiotic therapy
for 3-5 days were randomized to receive either a post-prescription review by the
infectious disease physician (IDP), followed by a recommendation to the attending
physician to modify the prescription when appropriate, or no systematic review of
the prescription. In the intervention group, 63.3% of prescriptions prompted IDP
recommendations, which were mostly followed by ward physicians (90.3%). Early
antibiotic modifications were more frequent in the intervention group (57.1% vs.
25.7%, p <0.0001), including stopping therapy, shortening duration and de
escalating broad-spectrum antibiotics. IDP intervention led to a significant
reduction of the median [IQR] duration of antibiotic therapy (6 [4-9] vs. 7 days
[5-9], p <0.0001). In-hospital mortality, ICU admission and new course of
antibiotic therapy rates did not differ between the two groups. Fewer patients in
the intervention group were readmitted for relapsing infection (3.4% vs. 7.9%, p
0.01). There was a trend for a shorter length of hospital stay in patients
suffering from community-acquired infections in the intervention group (5 days [3
10] vs. 6 days [3-14], p 0.06). This study provides clinical evidence that a post
prescription antibiotic review followed by unsolicited IDP advice is effective in
reducing antibiotic exposure of patients and increasing the quality of antibiotic
use, and may reduce hospital stay and relapsing infection rates, with no adverse
effects on other patient outcomes.
PMID- 23153411
TI - Aggregation and dynamics of oligocholate transporters in phospholipid bilayers
revealed by solid-state NMR spectroscopy.
AB - Macrocycles made of cholate building blocks were previously found to transport
glucose readily across lipid bilayers. In this study, an (15)N, (13)Calpha
labeled glycine was inserted into a cyclic cholate trimer and attached at the end
of a linear trimer, respectively. The isotopic labeling allowed us to use solid
state NMR spectroscopy to study the dynamics, aggregation, and depth of insertion
of these compounds in lipid membranes. The cyclic compound was found to be mostly
immobilized in DLPC, POPC/POPG, and POPC/POPG/cholesterol membranes, whereas the
linear trimer displayed large-amplitude motion that depended on the membrane
thickness and viscosity. (13)C-detected (1)H spin diffusion experiments revealed
the depth of insertion of the compounds in the membranes, as well as their
contact with water molecules. The data support a consistent stacking model for
the cholate macrocycles in lipid membranes, driven by the hydrophobic
interactions of the water molecules in the interior of the macrocycles. The study
also shows a strong preference of the linear trimer for the membrane surface,
consistent with its lack of transport activity in earlier liposome leakage
assays.
PMID- 23153412
TI - Reactive transport modeling of chromium isotope fractionation during Cr(VI)
reduction.
AB - Chromium isotope fractionation is indicative of mass-transfer processes, such as
reduction of Cr(VI) to Cr(III) during groundwater remediation. Laboratory
experiments comparing batch and column treatment of Cr(VI) using organic carbon
suggest that the associated isotope fractionation may be influenced by solute
transport mechanisms. These batch and column experiments were simulated using the
reactive transport model MIN3P to further evaluate the effects of Cr reduction
and transport on isotope fractionation under saturated flow conditions.
Simulation of the batch experiment provided a good fit to the experimental data,
where a fractionation factor (alpha53) of 0.9965 was attributed to a single,
dominant Cr(VI) removal mechanism. Calibration of the column simulations to the
experimental results suggested the presence of a second, more rapid Cr(VI)
removal mechanism with alpha53 = 0.9992. Results from this study demonstrate that
the interpretation of Cr isotope fractionation during reduction can be complex,
particularly where multiple removal mechanisms are evident. Reactive transport
modeling of Cr isotope fractionation can provide a quantitative assessment of the
contaminant removal mechanisms, thus improving the application of Cr isotope
measurements as a tool to track Cr(VI) migration and attenuation in groundwater.
PMID- 23153413
TI - [The Mexican consensus on gastroesophageal reflux disease. Part I].
AB - BACKGROUND: The changes, advances, and new discoveries regarding different
aspects of gastroesophageal reflux disease (GERD) have made it necessary to
update the Mexican Consensus published in 2002. AIMS: To elaborate a new Mexican
Consensus on GERD. METHODS: The general project coordinators selected six GERD
experts to carry out an extensive review of the literature for the purpose of
elaborating statements on the principal aspects of GERD. These were then placed
under the consideration of specialists in the study of this disease. Definitive
approval by all participants was reached using the modified Delphi method with
three rounds of anonymous and iterative voting. The following scale was employed:
A- in complete agreement; B- in agreement, but with minor concerns; C- in
agreement, but with major concerns; D- in disagreement, but with major concerns;
E- in disagreement, but with minor concerns; or F- in complete disagreement.
Consensus was declared when 67.00% or more of the participants concurred on a
category of agreement (A, B, or C). RESULTS: A consensus was reached on 160 of
the statements upon completion of the voting rounds, with 90.00% concurrence for
the majority of them. CONCLUSIONS: The 2011 Mexican Consensus on Gastroesophageal
Disease is a practical and up-to-date consultation tool, providing the opinion of
Mexican experts on all the new information available about this disease. It
allows there to be homogeneity in diagnostic and therapeutic criteria, all of
which serves to benefit our patients.
PMID- 23153414
TI - [Clostridium difficile: Is it time to start worrying?].
PMID- 23153415
TI - [The "rendez-vous" maneuver as a technical option to access the bile ducts: case
series report].
AB - The "rendez-vous" maneuver is a technical option, to have in mind, for the bile
ducts access. This technique assures a "guided" canulation of the bile duct
during the laparoscopic cholecystectomy (LC). We analyzed three clinical cases of
patients with cholecysto-choledocolithiasis, in whose were planned Endoscopic
Retrograde Cholangio-Pancreatography (ERCP) and LC during the same surgical
intervention. The "rendez-vous" maneuver was employed as a technical option to
access the bile duct, after an initial (failed) endoscopic attempt of
cannulation. An intraoperative cholangiography was performed and a guide wire was
inserted through the cystic duct, allowing the endoscopic capture and the guided
cannulation of the bile duct. The therapeutic objective was achieved in all
patients. There was not associated morbid-mortality and all patients were
satisfied with the surgical outcome. In these series of cases, the "rendez-vous"
maneuver was a viable, safe and useful technical option to access the bile ducts.
Futhermore, the cholecysto-choledocolithiasis was treated during the same
surgical intervention. A postoperative bile duct exploration becomes unnecessary.
PMID- 23153416
TI - [Blue rubber bleb nevus syndrome: A case report].
AB - Blue Rubber Bleb Nevus Syndrome (BRBS) is a rare disease, characterized by
multiple vascular malformations in the skin and gastrointestinal tract. Other
organs can also be affected, presenting different clinical manifestations such as
arthralgia, epistaxis, hemoptysis, hematuria, hemothorax, mild thrombocytopenia,
consumptive coagulopathy, and bone deformities, among others. We present a case
of BRBS in a nine-year-old boy with the characteristic clinical manifestations of
punctated purplish-blue skin lesions that vary in size and gastrointestinal
vascular malformations with upper digestive tract bleeding.
PMID- 23153417
TI - An ECM-based culture system for the generation and maintenance of xeno-free human
iPS cells.
AB - Pluripotent stem cells (PSCs) including induced pluripotent stem cells (iPSCs)
and embryonic stem cells (ESCs) have emerged as a promising source for treating
incurable diseases. Problems that urgently need to be resolved before the
clinical application include avoiding potential xenopathogenic transmission and
immune rejection that may be caused by the exposure of PSCs to animal-derived
products. In addition, an efficient feeder cell-free culture condition would be
required for reducing batch-to-batch variation and facilitating scale-up.
Therefore, establishing an efficient xeno-free and extracelluar matrix-based
culture system is a prerequisite for the clinical application of PSCs. In this
study, by blocking protein kinase C and histone deacetylase activities, we
formulated a medium that, in combination with vitronectin as an extracellular
matrix, not only allows the long-term culture of hESCs and iPSCs but also
efficiently generates xeno-free iPSCs. This xeno-free and feeder cell-free
culture system would facilitate the clinical applications of both iPSC- and ESC
based cell therapies in the future.
PMID- 23153418
TI - The effect of graphene oxide on conformation change, aggregation and cytotoxicity
of HIV-1 regulatory protein (Vpr).
AB - The fragment of viral protein R (Vpr), Vpr13-33, plays an important role in
regulating nuclear importing of HIV through ion channel formation with a leucine
zipper-like alpha-helical conformation. Herein we report an approach to reduce
cytotoxicity of Vpr13-33 by graphene oxide induced conformation change and
aggregation. Preferential adsorption of Vpr13-33 on graphene oxide accompanied by
conformation change from alpha-helix to beta-sheet structures has been observed
by using atomic force microscopy (AFM) and circular dichroism (CD). The
submolecular structures of the Vpr13-33 peptide assembly on graphite surface have
been identified by using scanning tunneling microscopy (STM), which confirms the
beta-sheet structures of Vpr13-33 on graphene oxide surface. The reduced
cytotoxicity of Vpr13-33 to neuroblastoma cells and T cells are detected by MTT
assay, which could be associated with the conformation change and stimulated
aggregation of Vpr13-33 upon addition of graphene oxide through hydrophobic
interaction. Furthermore, fluorescent leakage assay by using large unilamellar
vesicles (LUVs) indicated that the GO reduced Vpr13-33-induced cytotoxicity could
be associated with the inhibited "pore forming" function of Vpr13-33 by
conformation change and aggregation.
PMID- 23153420
TI - Fibroblast growth factor 2 induces the precocious development of endothelial cell
networks in bovine luteinising follicular cells.
AB - The transition from follicle to corpus luteum represents a period of intense
angiogenesis; however, the exact roles of angiogenic factors during this time
remain to be elucidated. Thus, the roles of vascular endothelial growth factor
(VEGF) A, fibroblast growth factor (FGF) 2 and LH in controlling angiogenesis
were examined in the present study. A novel serum-free luteinising follicular
angiogenesis culture system was developed in which progesterone production
increased during the first 5 days and was increased by LH (P<0.01). Blockade of
signalling from FGF receptors (SU5402; P<0.001) and, to a lesser extent, VEGF
receptors (SU1498; P<0.001) decreased the development of endothelial cell (EC)
networks. Conversely, FGF2 dose-dependently (P<0.001) induced the precocious
transition of undeveloped EC islands into branched networks associated with a
twofold increase in the number of branch points (P<0.001). In contrast, VEGFA had
no effect on the area of EC networks or the number of branch points. LH had no
effect on the area of EC networks, but it marginally increased the number of
branch points (P<0.05) and FGF2 production (P<0.001). Surprisingly, progesterone
production was decreased by FGF2 (P<0.01) but only on Day 5 of culture.
Progesterone production was increased by SU5402 (P<0.001) and decreased by SU1498
(P<0.001). These results demonstrate that FGF and VEGF receptors play a
fundamental role in the formation of luteal EC networks in vitro, which includes
a novel role for FGF2 in induction of EC sprouting.
PMID- 23153419
TI - Inflammation and diabetes-accelerated atherosclerosis: myeloid cell mediators.
AB - Monocytes and macrophages respond to and govern inflammation by producing a
plethora of inflammatory modulators, including cytokines, chemokines, and
arachidonic acid (C20:4)-derived lipid mediators. One of the most prevalent
inflammatory diseases is cardiovascular disease, caused by atherosclerosis, and
accelerated by diabetes. Recent research has demonstrated that
monocytes/macrophages from diabetic mice and humans with type 1 diabetes show
upregulation of the enzyme, acyl-CoA synthetase 1 (ACSL1), which promotes C20:4
metabolism, and that ACSL1 inhibition selectively protects these cells from the
inflammatory and proatherosclerotic effects of diabetes, in mice. Increased
understanding of the role of ACSL1 and other culprits in monocytes/macrophages in
inflammation and diabetes-accelerated atherosclerosis offers hope for new
treatment strategies to combat diabetic vascular disease.
PMID- 23153421
TI - Early discharge does not increase readmission or mortality after high-risk
vascular surgery.
AB - PURPOSE: Clinical pathways aimed at reducing hospital length of stay following
vascular surgery have been broadly implemented to reduce costs. However, early
hospital discharge may adversely affect the risk of readmission or mortality. To
address this question, we examined the relationship between early discharge and
30-day outcomes among patients undergoing a high-risk vascular surgery procedure,
thoracic aortic aneurysm (TAA) repair. METHODS: Using Medicare claims from 2000
to 2007, we identified all patients who were discharged home following elective
thoracic endovascular aneurysm repair (TEVAR) and open repair for nonruptured
TAAs. For each procedure, we examined the correlation between early discharge (<3
days for TEVAR, <7 days for open TAA repair) and 30-day readmission, 30-day
mortality, and hospital costs. Predictors of readmission were evaluated using
logistic regression models controlling for patient comorbidities, perioperative
complications, and discharge location. RESULTS: Our sample included 9764
patients, of which 7850 (80%) underwent open TAA repair, and 1914 (20%) underwent
TEVAR. Patients discharged to home early were more likely to be female (66% early
vs 56% late), Caucasian (94% early vs 91% late), younger (73 years early vs 74
years late), and have fewer comorbidities (mean Charlson score: 0.7 early vs 1.0
late) than patients discharged home late (all P < .01). As compared with patients
who were discharged late, patients discharged home early following uncomplicated
open TAA repair and TEVAR had significantly lower 30-day readmission rates
([open: 17% vs 24%; P < .001] [TEVAR: 12% vs 23%; P < .001]) and hospital costs
([open: $73,061 vs $136,480; P < .001] [TEVAR: $58,667 vs $128,478; P < .001]),
without an observed increase in 30-day postdischarge mortality. In multivariable
analysis, early hospital discharge was associated with a significantly lower
likelihood of readmission following both open TAA repair (odds ratio, 0.70; 95%
confidence interval, 0.57-0.85; P < .001) and TEVAR (odds ratio, 0.57; 95%
confidence interval, 0.38-0.85; P < .01) procedures. CONCLUSIONS: Discharging
patients home early following uncomplicated TEVAR or open TAA repair is
associated with reduced hospital costs without adversely impacting 30-day
readmission or mortality rates. These data support the safety and cost
effectiveness of programs aimed at early hospital discharge in selected vascular
surgery patients.
PMID- 23153422
TI - Current status and future developments of contrast-enhanced ultrasound of carotid
atherosclerosis.
AB - B-mode and Doppler ultrasound are commonly used for the evaluation of
atherosclerosis in the carotid arteries. Recently, contrast-enhanced ultrasound
(CEUS) has been introduced as a technique to improve the detection of carotid
atherosclerosis and evaluate the presence of intraplaque neovascularization,
which is considered a marker of plaque vulnerability. The present review focuses
on the role of CEUS for the assessment of atherosclerosis and plaque instability.
Currently available literature and future developments with CEUS are discussed.
PMID- 23153423
TI - Primary balloon angioplasty of small (<=2 mm) cephalic veins improves primary
patency of arteriovenous fistulae and decreases reintervention rates.
AB - PURPOSE: The purpose of this study was to evaluate the effect of primary balloon
angioplasty (PBA) of cephalic veins with diameter<=2 mm on patency and maturation
time of autogenous radiocephalic arteriovenous fistulae (AVF) for hemodialysis.
METHODS: Forty patients, all candidates for distal AVF, with a cephalic vein<=2
mm, were randomized to two different surgical procedures: (1) PBA of a long
segment of the cephalic vein from the wrist up to the elbow (n=19); and (2)
hydrostatic dilatation (HD) of a short venous segment (5 cm) at the level of the
anastomosis (n=21). PBA was performed using a standard balloon 4*150 mm. Primary
end points were primary patency and reintervention rates. Secondary end points
were maturation time and the rate of working AVF. Follow-up included physical and
duplex ultrasound (DUS) examinations at 1,4, and 8 weeks, and every 3 months
thereafter. RESULTS: Risk factors were homogeneously distributed between the two
groups. Mean vein diameter was 1.8+/-0.2 mm for the PBA group and 1.7+/-0.2 mm
for HD. Immediate success rate was 100% for PBA and 67% for HD groups (P=.04).
Causes of failure in the HD group included early vein thrombosis in seven
patients (33%). Mean fistula maturation time was 32 days in the PBA group and 55
days in the HD group (P=.04). During the mean follow-up of 7 months, three
patients underwent drug-eluting balloon angioplasty for failure of AVF to mature
due to stenosis (1 in the PBA group and 2 in the HD group). Six-month
reintervention rate was significantly lower in the PBA group (5%) compared with
the HD group (43%) (P=.02). At 6 months, primary patency rates were 95% in the
PBA group and 57% in the HD group (P=.01). Working AVF rate was 100% in the PBA
vs 90% in the HD group. CONCLUSIONS: PBA of very small cephalic veins during the
creation of a distal AVF for hemodialysis is a safe and feasible procedure. This
technique assures excellent primary patency, maturation time, and dramatically
decreases reintervention rate.
PMID- 23153424
TI - [Surgical treatment of liver metastases of gastric cancer].
AB - INTRODUCTION: Gastric cancer, despite of its decreasing incidence, remains a
serious medical problem. Many patients see a specialist as late as in the IVth
stage of the disease with peritoneal seedings or liver metastases. Liver
resection for gastric cancer metastases remains to be a controversial issue.
MATERIAL AND METHODS: The aim of this study is to present, through our case
report and literature review, the current opinions on liver resections for
metastatic gastric cancer. RESULTS: Based on our experience and review of the
Medline literature of the last five years, we would like to present the current
trends in this field. CONCLUSIONS: Liver resection for gastric cancer metastases
remains a controversial topic. However, in a very carefully selected group of
patients, improved survival can be reached by combining liver resection and
modern systemic treatment.
PMID- 23153425
TI - [Delayed gastric emptying after partial duodenopancreatectomy].
AB - INTRODUCTION: Delayed gastric emptying (DGE) is a relatively common complication
in patients after partial duodenopancreatectomy (PDPE) and significantly
contributes to their postoperative morbidity. There has only been a small amount
of interest attributed to DGE in Czech literature. The aim of this article is to
present and analyze our own experience with the occurrence of DGE after PDPE.
MATERIALS AND METHODS: Retrospective analysis of prospectively collected data
from 106 patients who underwent a PDPE at the Department of Surgery, University
Hospital Motol and 2nd Medical Faculty, between 2001 and 2011. The data were
statistically analyzed using the Chi-square test with statistical significance
set at 5% of probability value (p < 0.05). RESULTS: During the reporting period,
PDPE was performed in 106 patients with a pathological process in the pancreatic
head. 4 patients died in the postoperative period (30-day mortality 3.8%). Major
postoperative complications occurred in 31 patients (morbidity 29%), with
clinically significant DGE (grade B and C) in almost half of them (16 patients).
Along with the DGE, 4 patients suffered from other major complications (2
pancreatic anastomotic insufficiency, 1 bile fistula and 1 external pancreatic
fistula). We did not prove a statistically significant difference in the
incidence of DGE depending either on the type of resection or pancreatic
anastomosis type. CONCLUSION: DGE contributes significantly to postoperative
morbidity in patients after PDPE and is associated with other serious
postoperative complications in a considerable number of cases.
PMID- 23153426
TI - [K-ras mutational status and tumour-infiltrating lymphocytes in human colon
cancer: state of the art and future perspectives].
AB - INTRODUCTION: Nowadays, the prognosis of newly diagnosed colorectal cancer
patients relies mostly on the tumour-node-metastasis (TNM) classification which
is also a determining criterion for the indication of adjuvant oncological
treatment. Currently, new prognostic and predictive biomarkers are sought after
in order to more precisely define prognosis and better predict the benefits of
adjuvant treatment in colorectal cancer. Besides several molecular biomarkers,
such as mutations in the proto-oncogene K-ras, analyses of tumour-infiltrating
lymphocytes have shown promising prognostic value. The aim of the study is to
examine the correlations between K-ras mutational status and tumour-infiltrating
immune cells in colon cancer patients with respect to colon cancer recurrence.
MATERIAL AND METHODS: Formalin-fixed paraffin-embedded specimens were obtained
from 44 patients with surgically resected colon cancer (R0 resection) treated
between 2004 and 2009. K-ras mutational status was detected using PCR
amplification of exon 1 followed by direct sequencing and K-ras StripAssay.
Tumour-infiltrating immune cells were detected by immunofluorescence staining
using monoclonal antibodies against CD3, CD8, FoxP3, CD1a and DC-LAMP. RESULTS:
All 44 patients in our cohort underwent radical resection of colon cancer. In 16
patients the tumour relapsed (36.4%). K-ras mutations were found in 45.5% (n=20)
of the primary carcinomas: 65% in codon 12 and 35% in codon 13. Although codon 13
K-ras mutations were associated with disease relapse, they were present in both
disease-free and relapsed patients. However, disease-free and relapsed patients
differed markedly in their patterns of tumour-infiltrating immune cells. There
was a trend towards decreased density of tumour-infiltrating lymphocytes within
the group of relapsed patients. In addition, relapsed patients with codon 13
mutations had markedly lower levels of tumour-infiltrating mature DC-LAMP+
dendritic cells and higher frequency of CD1a+ cells compared to disease-free
patients. CONCLUSION: Colon cancer patients with low levels of tumour
infiltrating lymphocytes, a high CD1a+/DC-LAMP+ tumour-infiltrating DC ratio and
a K-ras mutation in codon 13 are at a high risk of disease recurrence.
PMID- 23153427
TI - [Injury to the abdominal wall by a foreign body with a late perforation of the
GIT].
AB - The authors present the case of a patient with an abdominal puncture wound who
developed, in two weeks, perforation of the colon with an unrecognized foreign
body in the abdominal cavity.
PMID- 23153428
TI - [Complications of breast augmentation - a case report].
AB - As with any surgery, breast augmentation does have certain risks and
complications. The aim of this article is to point out a rare complication of
breast augmentation - axillary silicone lymphadenopathy (defined as the presence
of silicone in the lymph nodes). The authors present a case report of silicone
lymphadenopathy in a young woman after the rupture of a silicone breast implant.
As the number of women with breast implants is increasing, it is necessary to
bear this rare complication of breast augmentation in mind in differential
diagnosis of axillary lymphadenopathy.
PMID- 23153430
TI - [Endoscopic therapy of early gastric carcinoma].
PMID- 23153431
TI - [Surgical treatment of gastric carcinoma].
PMID- 23153432
TI - [Surgical treatment of gastroesophageal junction tumors].
PMID- 23153433
TI - [Laparoscopic surgery for gastric carcinoma].
PMID- 23153434
TI - [Use of laser Doppler to assess peripheral tissue perfusion in critically ill
children].
AB - OBJECTIVE: To analyze skin tissue perfusion at different sites in critically ill
children. PATIENTS AND METHODS: A prospective observational study was performed
on 41 critically ill children with a median age of 12 months and weight of 8.2
kg. Skin tissue flow was measured in each patient using laser Doppler
consecutively in the foot, forearm, thigh and hypochondrium, and its association
with demographic and hemodynamic variables, as well as lactate and inotropic
index, was analyzed. RESULTS: A total of 144 tissue flow measurements were made,
with a median flow of 3.2+/-2.2 ml/min/100 g tissue. There was a moderate
correlation between the tissue flow measured in central locations, abdomen-arm
(r(2): 0.574, P=.001), abdomen-thigh (r(2): 0.423, P=.002) and thigh-arm (r(2):
0.703, P<.000), but not with the peripheral measurements (sole of the foot). The
limits of agreement, measured between the different locations, were wide (range
6.1 to -2.5 ml/min/100g). There was a slight-moderate correlation between the
flow in the sole of the foot with weight (-0.355, P=.039), age (-0.343, P=.044),
peripheral temperature (0.503, P=.017) and inotropic index (-0.443, P=.008).
CONCLUSIONS: Tissue flow in the foot correlates with weight, age, peripheral
temperature and inotropic index. Further studies are needed to analyze its
usefulness in assessing peripheral perfusion in situations of shock.
PMID- 23153435
TI - Fasting blood glucose and insulin sensitivity are unaffected by HAART duration in
Cameroonians receiving first-line antiretroviral treatment.
AB - AIMS: This study assessed the relationship between highly active antiretroviral
therapy (HAART) duration and cardiometabolic disorders in HIV-infected
Cameroonians. METHODS: HIV-infected Cameroonians aged 21 years or above were
cross-sectionally recruited at the Yaounde Central Hospital, a certified HIV care
centre, and their anthropometry, body composition (impedancemetry), fasting blood
glucose (FBG) and lipid levels, and insulin sensitivity (IS; short insulin
tolerance test) were measured. RESULTS: A total of 143 participants with various
durations of HAART [treatment-naive (n=28), 1-13 months (n=44), 14-33 months
(n=35) and 34-86 months (n=36)] were recruited. They were mostly women (72%), and
had a mean age of 39.5 (SD: 9.8) years. Half (52%) were using a stavudine
containing regimen. There was a significant trend towards a positive change in
body mass index and waist-to-hip ratio with increasing duration of HAART (all
P=0.02). Systolic (P=0.04) and diastolic (P=0.03) blood pressure, total
cholesterol (P=0.01), prevalence of hypertension (P=0.04) and
hypercholesterolaemia (P=0.007) were also significantly increased with HAART
duration, whereas triglycerides, FBG and IS were unaffected. Clustering of
metabolic disorders increased (P=0.02 for >=1 component of the metabolic syndrome
and P=0.09 for >=2 components) with HAART duration. CONCLUSION: HAART duration is
associated with obesity, fat distribution, blood pressure and cholesterol levels
in HIV-infected Cameroonians, but does not appear to significantly affect glucose
metabolism.
PMID- 23153436
TI - Lgr5 is a potential marker of colorectal carcinoma stem cells that correlates
with patient survival.
AB - BACKGROUND: Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5)
has recently been identified as an intestinal stem cell marker. In order to
determine whether Lgr5 is a potential marker of cancer stem cells, we
investigated whether Lgr5 expression correlated with Ki-67 expression and
prognosis in colorectal carcinoma. METHODS: Lgr5 and Ki-67 expression were
evaluated by immunohistochemistry in 192 colorectal carcinoma specimens.
Selection of side population (SP) cells was performed by staining with Hoechest
33342, and Lgr5 expression in Colo205 SP cells was then detected by
immunofluorescence. RESULTS: Lgr5 expression was significantly higher in
carcinoma than in normal mucosa (P=0.001). Lgr5 was positively correlated with
histological grade (P=0.001), depth of invasion (P=0.001), lymph node metastasis
(P=0.001), distant metastasis (P=0.004), pTNM stage (P=0.001), and Ki-67
(r=0.446, P=0.001). Multivariate analysis showed that the effect of Lgr5 on
survival was independent of Ki-67 (P=0.037). In the in vitro study, Hoechst low
staining cells were counted in 7% of the Colo205 colon cancer cell line
population, and Lgr5 expression was strikingly stronger in Hoechst low-staining
cells than in high-staining cells (P=0.001). CONCLUSIONS: These findings suggest
that Lgr5 may play an important role in the progression and prognosis of
colorectal carcinoma, and may be a potential new therapeutic target for the
treatment of colorectal cancer patients. It may also be considered as a potential
marker for colorectal cancer stem cells (CSCs).
PMID- 23153437
TI - Safety and immunogenicity of the pneumococcal pneumolysin derivative PlyD1 in a
single-antigen protein vaccine candidate in adults.
AB - BACKGROUND: Pneumococcal vaccines based on conserved protein antigens have the
potential to offer expanded protection against Streptococcus pneumoniae.
OBJECTIVE: This study examined the safety and immunogenicity in adults of three
doses of a pneumococcal single-antigen protein vaccine candidate formulated with
aluminum hydroxide adjuvant and recombinantly derived, highly detoxified,
genetically mutated pneumolysin protein (PlyD1). METHODS: This phase I,
randomized, placebo-controlled, observer-blinded, dose-escalating study enrolled
adults (18-50 years). In a pilot safety study, participants received a single
injection of 10 MUg PlyD1 and were observed for 24 h. Following review of the
pilot safety data, participants were randomized (2:1) to receive two injections
of PlyD1 at one of three doses or placebo 30 days apart. Assignment of second
injection and successive dose cohorts was made after blinded safety reviews after
each injection at each dose level. Safety endpoints included rates of solicited
injection site reactions, solicited systemic reactions, unsolicited adverse
events (AEs), serious AEs (SAEs), and safety laboratory tests. Immunogenicity
endpoints included geometric mean concentrations of anti-PlyD1 IgG as determined
by ELISA and functional assessment in an in vitro toxin neutralization assay.
RESULTS: The study included a total of 100 participants, including 10 in the
pilot study and 90 in the randomized study. None of the participants in the pilot
study had SAEs, allergic reactions, or other safety concerns. Ninety participants
received two doses of or placebo (n=30) or active vaccine candidate at 10 (n=20),
25 (n=20), or 50 MUg (n=20). No vaccine-related SAE or discontinuation due to an
AE occurred. Most solicited reactions were mild and transient. The most
frequently reported solicited reactions were pain at the injection site and
myalgia. Antigen-specific IgG levels and functional activity showed dose-related
increases. When comparing the three dose levels, a plateau effect was observed at
the 25 MUg dose. CONCLUSIONS: All dose levels were safe and immunogenic. Repeat
vaccination significantly increased the level of anti-PlyD1 antibodies.
Functional antibody activity was demonstrated in sera from vaccinated individuals
(ClinicalTrials.gov no. NCT01444352).
PMID- 23153438
TI - Yersinia enterocolitica ghost with msbB mutation provides protection and reduces
proinflammatory cytokines in mice.
AB - Yersinia enterocolitica is an important human pathogen. Yersiniosis, caused by Y.
enterocolitica, has become more prevalent globally in recent years. Prevention of
yersiniosis still remains a challenge, and an efficacious and safe vaccine that
confers protection against this enteric pathogen needs to be developed. In this
study, a novel vaccine based on the bacterial ghost, in combination with mutation
of the Y. enterocolitica msbB gene, was developed and the immunopotency of this
vaccine was evaluated in mice. Significant levels of IgG1/IgG2a antibodies and IL
4/IFN-gamma cytokines were detected after mice were administered this vaccine
intragastrically, indicating that a Th1/Th2-mediated mixed immune response was
stimulated. Importantly, mutation of the msbB gene efficiently reduced secretion
of the proinflammatory cytokines IL-1beta, IL-6 and TNF-alpha, suggesting a
reduction in inflammatory reaction caused by lipopolysaccharide. In addition,
when challenged with a dose that was 100-fold the minimal lethal dose of the
virulent wild strain of Y. enterocolitica, this mutated ghost vaccine was capable
of eliciting the same effective protection (80%) in comparison with the non
mutated ghost strain, and the survival time was extended by at least two days.
Together, our results demonstrated that this novel ghost bacterial strain could
be used as a safe and effective vaccine against Y. enterocolitica.
PMID- 23153439
TI - Cost-effectiveness of adult pneumococcal vaccination: responding to: Weycker D,
Sato R, Strutton D, Edelsberg J, Atwood M, Jackson LA. Public health and economic
impact of 13-valent pneumococcal conjugate vaccine in US adults aged >=50 years.
Vaccine 2012;30(August (36)):5437-44.
PMID- 23153440
TI - Low opsonic activity to the infecting serotype in pediatric patients with
invasive pneumococcal disease.
AB - Serotype-specific protective immunity in pediatric patients with invasive
pneumococcal disease (IPD) has not been fully investigated. To determine the
protective immunity to the infecting serotype, the serotype-specific
immunoglobulin G (IgG) levels and opsonization indices (OIs) were examined in 24
Japanese pediatric patients whose serum was collected within one month of an IPD
episode between May 2008 and June 2011. The median age (range) of IPD patients
was 17 (10-108) months and 63% were boys. In all 17 patients tested, the levels
of serotype-specific IgG to the infecting serotype were higher than 0.2 MUg/ml,
but the OIs to the infecting serotype were <8. The avidities of 19F- or 6B
specific IgG in patients with levels higher than 5.0 MUg/ml, but with
undetectable OIs, were confirmed to be lower than those in patients with high
OIs. Our data demonstrated that although the levels of serotype-specific IgG to
the infecting serotype were higher than 0.2 MUg/ml in sera of pediatric patients
with IPD, the OIs were low one month after the IPD episode. Low opsonic
activities in these patients may, in part, be explained by the low avidity of
serotype-specific IgG.
PMID- 23153441
TI - Comprehensive evaluation of the adenovirus/alphavirus-replicon chimeric vector
based vaccine rAdV-SFV-E2 against classical swine fever.
AB - Classical swine fever (CSF) is an economically important, highly contagious swine
disease caused by classical swine fever virus (CSFV). Marker vaccines and
companion serological diagnostic tests are thought to be a promising strategy for
future control and eradication of CSF. Previously, we have demonstrated that an
adenovirus-vectored Semliki forest virus replicon construct expressing the E2
glycoprotein from CSFV, rAdV-SFV-E2, induced sterile immunity against a lethal
CSFV challenge. In this study, we further evaluated the vaccine with respect to
its safety, number and dose of immunization, and effects of maternally derived
antibodies, re-immunization of the vaccine or co-administration with pseudorabies
vaccine on the vaccine efficacy. The results showed that: (1) the vaccine was
safe for mice, rabbits and pigs; (2) two immunizations with a dose as low as
6.25*10(5) TCID(50) or a single immunization with a dose of 10(7) TCID(50) rAdV
SFV-E2 provided complete protection against a lethal CSFV challenge; (3)
maternally derived antibodies had no inhibitory effects on the efficacy of the
vaccine; (4) the vaccine did not induce interfering anti-vector immunity; and (5)
co-administration of rAdV-SFV-E2 with a live pseudorabies vaccine induced
antibodies and protection indistinguishable from immunization with either vaccine
administered alone. Taken together, the chimeric vaccine represents a promising
marker vaccine candidate for control and eradication of CSF.
PMID- 23153442
TI - Acinetobacter baumannii rOmpA vaccine dose alters immune polarization and
immunodominant epitopes.
AB - BACKGROUND: The rOmpA vaccine has been shown to protect mice from lethal
infection caused by extreme-drug-resistant (XDR) Acinetobacter baumannii. The
role of dose in immunology of the rOmpA vaccine was explored. METHODS: Mice were
vaccinated with various doses of rOmpA plus aluminum hydroxide (Al(OH)(3))
adjuvant. The impact of dose on antibody titers, cytokine production, and
immunodominant epitopes was defined. RESULTS: Anti-rOmpA IgG and IgG subtype
titers were higher at larger vaccine doses (30 and 100 MUg vs. 3 MUg). The 3 MUg
dose induced a balanced IFN-gamma-IL-4 immune response while the 100 MUg dose
induced a polarized IL-4/Type 2 response. Epitope mapping revealed distinct T
cell epitopes that activated IFN-gamma-, IL-4-, and IL-17-producing splenocytes.
Vaccination with the 100 MUg dose caused epitope spreading among IL-4-producing
splenocytes, while it induced fewer reactive epitopes among IFN-gamma-producing
splenocytes. CONCLUSIONS: Vaccine dose escalation resulted in an enhanced Type 2
immune response, accompanied by substantial IL-4-inducing T cell epitope
spreading and restricted IFN-gamma-inducing epitopes. These results inform
continued development of the rOmpA vaccine against A. baumannii, and also are of
general importance in that they indicate that immune polarization and epitope
selectivity can be modulated by altering vaccine dose.
PMID- 23153444
TI - The role of non-viral antigens in the cotton rat model of respiratory syncytial
virus vaccine-enhanced disease.
AB - In the 1960s, infant immunization with a formalin-inactivated respiratory
syncytial virus (FI-RSV) vaccine candidate caused enhanced respiratory disease
(ERD) following natural RSV infection. Because of this tragedy, intensive effort
has been made to understand the root causes of how the FI-RSV vaccine induced a
pathogenic response to subsequent RSV infection in vaccinees. A well-established
cotton rat model of FI-RSV vaccine-enhanced disease has been used by numerous
researchers to study the mechanisms of ERD. Here, we have dissected the model and
found it to have significant limitations for understanding FI-RSV ERD. This view
is shaped by our finding that a major driver of lung pathology is cell-culture
contaminants, although FI-RSV immunization and RSV challenge serve as co-factors
to exacerbate disease. Specifically, non-viral products from the vaccine and
challenge preparations that are devoid of RSV give rise to alveolitis, which is
considered a hallmark of FI-RSV ERD in the cotton rat model. Although FI-RSV
immunization and RSV challenge promote more severe alveolitis, they also drive
stronger cellular immune responses to non-viral antigens. The severity of
alveolitis is associated with T cells specific for non-viral antigens more than
with T cells specific for RSV. These results highlight the limitations of the
cotton rat ERD model and the need for an improved animal model to evaluate the
safety of RSV vaccine candidates.
PMID- 23153443
TI - Safety and immunogenicity of recombinant Rift Valley fever MP-12 vaccine
candidates in sheep.
AB - The safety and immunogenicity of two authentic recombinant (ar) Rift Valley fever
(RVF) viruses, one with a deletion in the NSs region of the S RNA segment (arMP
12DeltaNSs16/198) and the other with a large deletion of the NSm gene in the pre
Gn region of the M RNA segment (arMP-12DeltaNSm21/384) of the RVF MP-12 vaccine
virus were tested in crossbred ewes at 30-50 days of gestation. First, we
evaluated the neutralizing antibody response, measured by plaque reduction
neutralization (PRNT(80)), and clinical response of the two viruses in groups of
four ewes each. The virus dose was 1*10(5)plaque forming units (PFU). Control
groups of four ewes each were also inoculated with a similar dose of RVF MP-12 or
the parent recombinant virus (arMP-12). Neutralizing antibody was first detected
in 3 of 4 animals inoculated with arMP-12DeltaNSm21/384 on Day 5 post inoculation
and all four animals had PRNT(80) titers of >=1:20 on Day 6. Neutralizing
antibody was first detected in 2 of 4 ewes inoculated with arMP-12DeltaNSs16/198
on Day 7 and all had PRNT(80) titers of >=1:20 on Day 10. We found the mean
PRNT(80) response to arMP-12DeltaNSs16/198 to be 16- to 25-fold lower than that
of ewes inoculated with arMP-12DeltaNSm21/384, arMP-12 or RVF MP-12. No abortions
occurred though a single fetal death in each of the arMP-12 and RVF MP-12 groups
was found at necropsy. The poor PRNT(80) response to arMP-12DeltaNSs16/198 caused
us to discontinue further testing of this candidate and focus on arMP
12DeltaNSm21/384. A dose escalation study of arMP-12DeltaNSm21/384 showed that
1*10(3)plaque forming units (PFU) stimulate a PRNT(80) response comparable to
doses of up to 1*10(5)PFU of this virus. With further study, the arMP
12DeltaNSm21/384 virus may prove to be a safe and efficacious candidate for a
livestock vaccine. The large deletion in the NSm gene may also provide a negative
marker that will allow serologic differentiation of naturally infected animals
from vaccinated animals.
PMID- 23153445
TI - Effectiveness of influenza vaccination in elderly diabetic patients: a
retrospective cohort study.
AB - PURPOSE: Studies regarding the clinical benefits of influenza vaccination in
diabetic patients are limited. This study evaluated if the elderly diabetic
patients who have had influenza vaccination would have benefits such as reduced
medical care and mortality. METHODS: We used the universal insurance claims data
from 2001 to 2009 in Taiwan to identify annual elderly patients with diabetes
cohorts with (N=4454) and without (N=4571) influenza vaccination. The risk of
developing pneumonia or influenza, respiratory failure, intensive care,
hospitalization, and mortality were measured and compared between cohorts within
one year of follow-up. RESULTS: The vaccine cohort had lower incidences of
pneumonia or influenza and respiratory failure compared with the non-vaccine
cohort. More importantly, the vaccine cohort had a hospitalization rate that was
11% less than the non-vaccine cohort (29.6 vs. 33.1 per 100 person-years) with an
adjusted hazard ratio (HR) of 0.88 (95% CI 0.81-0.96). The vaccine cohort was
also less likely to be admitted to the intensive care unit (ICU) [0.58 vs. 2.05
per 100 person-year; adjusted HR 0.30 (95% CI 0.19-0.47)] and less likely to
expire [3.13 vs. 7.96 per 100 person-year; adjusted HR 0.44 (95% CI 0.36-0.54)].
Influenza vaccination reduced the hospitalization cost by 1282.6 USD, compared
with patients without influenza vaccination (95% CI -2210.3, -354.8). CONCLUSION:
Influenza vaccination is associated with a reduced risk of morbidity,
hospitalization, ICU admissions, and mortality. In addition, the hospitalization
cost is reduced.
PMID- 23153446
TI - Reprint of: Serotyping and antibiotic susceptibility of Streptococcus pneumoniae
strains isolated in Algeria from 2001 to 2010.
AB - INTRODUCTION: Pneumococcal infections are a major public health problem because
of the virulence of this bacterium and its ability to develop resistance.
MATERIAL AND METHOD: Two hundred and ninety-four strains of Streptococcus
pneumoniae were isolated from sterile (56.8%) and non-sterile samples (43.2%),
from January 2001 to July 2010. RESULTS: The interpretation of antibiotic
susceptibility testing, according to CLSI criteria (M100-S21 2011), yielded a
25.2% overall resistance to penicillin, with 23.5% of strains isolated from CSF
(meningitis), and only 1.7% in other samples. Resistance to cefotaxime was 8.1%
(including 4.4% at a high level). The most common serotypes were: 14 (19.5%), 23F
(9.7%), 6B (9.3%), 19F (5.4%), and serotype 1 (5%). The percentage of these
serotypes isolated from normally sterile sites in children under 5 years of age
was 31.25% for 14, 10.4% for 23F, 8.3% for 19F, 6.25% for 6B, and 4.2% for
serotype 1. The theoretical vaccinal coverage against invasive infections in
children under 2 years of age was 61.5%, 69.2%, and 76.9% for the 7-valent, 10
valent, and 13-valent conjugate vaccines, respectively. Penicillin non
susceptible Streptococcus pneumoniae (PNSP) strains accounted for 67.1, 68.6, and
72.8% for each of these three vaccines. CONCLUSION: There was a variation of
serotype rates compared to previous studies. The increase in pneumococcal
antibiotic resistance is concerning, particularly for the treatment of
pneumococcal infections in children and infants. Pneumococcal vaccination is not
compulsory yet in Algeria.
PMID- 23153447
TI - Immune evasion strategies of flaviviruses.
AB - Flavivirus is a genus of the family Flaviviridae. It includes West Nile virus
(WNV), dengue virus (DENV), yellow fever virus (YFV), Japanese encephalitis virus
(JEV), tick-borne encephalitis virus (TBEV), and several other viruses which lead
to extensive morbidity and mortality in humans. To establish infection and
replication in the hosts, flaviviruses have evolved a variety of strategies to
modulate the host's immune responses. In this review, the strategies employed by
flaviviruses to evade the innate and adaptive immunity of host are summarized
based on current studies, with a major focus on the inhibition of interferon,
complement, natural killer (NK) cell, B cell, and T cell responses. This review
aims to provide an overview of the current understanding for the mechanisms used
by flaviviruses to escape the host's immune response, which will facilitate the
future studies on flavivirus pathogenesis and the development of anti-flavivirus
therapeutics.
PMID- 23153448
TI - Immune responses and protection in children in developing countries induced by
oral vaccines.
AB - Oral mucosal vaccines have great promise for generating protective immunity
against intestinal infections for the benefit of large numbers of people
especially young children. There however appears to be a caveat since these
vaccines have to overcome the inbuilt resistance of mucosal surfaces and
secretions to inhibit antigen stimulation and responses. Unfortunately, these
vaccines are not equally immunogenic nor protective in different populations.
When compared to industrialized countries, children living in developing
countries appear to have lower responses, but the reasons for these lowered
responses are not clearly defined. The most likely explanations relate to
undernutrition, micronutrient deficiencies, microbial overload on mucosal
surfaces, alteration of microbiome and microbolom and irreversible changes on the
mucosa as well as maternal antibodies in serum or breast milk may alter the
mucosal pathology and lower immune responses to interventions using oral
vaccines. The detrimental effect of adverse environment and malnutrition may
bring about irreversible changes in the mucosa of children especially in the
first 1000 days of life from conception to after birth and up to two years of
age. This review aims to summarize the information available on lowered immune
responses to mucosal vaccines and on interventions that may help address the
constraints of these vaccines when they are used for children living under the
greatest stress and under harmful adverse circumstances.
PMID- 23153449
TI - Safety and immunogenicity of a Sf9 insect cell-derived respiratory syncytial
virus fusion protein nanoparticle vaccine.
AB - OBJECTIVE: We performed a Phase 1 randomized, observer-blinded, placebo
controlled trial to evaluate the safety and immunogenicity of a recombinant
respiratory syncytial virus (RSV) fusion (F) protein nanoparticle vaccine.
METHODS: Six formulations with (5, 15, 30 and 60 MUg) and without (30 and 60 MUg)
aluminum phosphate (AdjuPhos) were administered intramuscularly on day 0 and 30
in a dose escalating fashion to healthy adults 18-49 years of age. Solicited and
unsolicited events were collected through day 210. Immunogenicity measures taken
at day 0, 30 and 60 included RSV A and B microneutralization, anti-F IgG,
antigenic site II peptide and palivizumab competitive antibodies. RESULTS: The
vaccine was well-tolerated, with no evident dose-related toxicity or attributable
SAEs. At day 60 both RSV A and B microneutralization was significantly increased
in vaccinees versus placebo. Across all vaccinees there was a 7- to 19-fold
increase in the anti-F IgG and a 7- to 24-fold increase in the antigenic site II
binding and palivizumab competitive antibodies. CONCLUSIONS: The RSV F
nanoparticle vaccine candidate was well tolerated without dose-related increases
in adverse events. Measures of immunity indicate that neutralization, anti-RSV F
IgG titers and palivizumab competing antibodies were induced at levels that have
been associated with decreased risk of hospitalization. NCT01290419.
PMID- 23153451
TI - Effects of fatty acids on angiogenic activity in the placental extravillious
trophoblast cells.
AB - Fatty acids regulate angiogenesis although no such information is available in
first trimester placental trophoblast cells despite the fact that angiogenesis is
a critical step involving these cells in early placentation. We investigated
effects of different fatty acids on angiogenesis, their uptake and metabolism and
expression of lipid metabolic genes in first trimester placental trophoblast
cells using HTR-8/SVneo cell line. Fatty acid uptake by these cells exhibited a
saturable kinetics. Uptake of AA was consistently greater compared with that of
EPA and DHA throughout the incubation period of 180 min. Use of triacsin C, an
inhibitor of acyl-CoA synthetase, significantly inhibited fatty acid uptake as
well as fatty acid induced cell proliferation in these cells. Angiogenic effect
(as measured by tube formation) of these fatty acids was in the following order
DHA> EPA> AA> OA. Angiogenic effect of these fatty acids (AA, EPA, OA) was
significantly decreased in ANGPTL4 knocked down cells, indicating ANGPTL4 may be
involved at least in part in fatty acid induced angiogenesis. In addition, these
fatty acids altered expression of several lipid metabolic genes such as ADRP,
FABP4, FABP3, and COX-2 those are involved in angiogenesis. All these data
suggest that fatty acids regulate angiogenic processes in these cells via
different mechanisms.
PMID- 23153450
TI - Adsorption of recombinant poxvirus L1-protein to aluminum hydroxide/CpG vaccine
adjuvants enhances immune responses and protection of mice from vaccinia virus
challenge.
AB - The stockpiling of live vaccinia virus vaccines has enhanced biopreparedness
against the intentional or accidental release of smallpox. Ongoing research on
future generation smallpox vaccines is providing key insights into protective
immune responses as well as important information about subunit-vaccine design
strategies. For protein-based recombinant subunit vaccines, the formulation and
stability of candidate antigens with different adjuvants are important factors to
consider for vaccine design. In this work, a non-tagged secreted L1-protein, a
target antigen on mature virus, was expressed using recombinant baculovirus
technology and purified. To identify optimal formulation conditions for L1, a
series of biophysical studies was performed over a range of pH and temperature
conditions. The overall physical stability profile was summarized in an empirical
phase diagram. Another critical question to address for development of an
adjuvanted vaccine was if immunogenicity and protection could be affected by the
interactions and binding of L1 to aluminum salts (Alhydrogel) with and without a
second adjuvant, CpG. We thus designed a series of vaccine formulations with
different binding interactions between the L1 and the two adjuvants, and then
performed a series of vaccination-challenge experiments in mice including
measurement of antibody responses and post-challenge weight loss and survival. We
found that better humoral responses and protection were conferred with vaccine
formulations when the L1-protein was adsorbed to Alhydrogel. These data
demonstrate that designing vaccine formulation conditions to maximize antigen
adjuvant interactions is a key factor in smallpox subunit-vaccine immunogenicity
and protection.
PMID- 23153452
TI - Knowledge and practice among Hong Kong oncology nurses in the management of
chemotherapy-induced nausea and vomiting.
AB - PURPOSE: To examine nurses' roles in the prevention and management of
chemotherapy-induced nausea and vomiting (CINV), and to identify their related
educational needs. METHODS: This was a descriptive cross-sectional study with a
self-reported survey completed by 103 oncology nurses caring for and
administering chemotherapy to cancer patients in the department of oncology in
three Hong Kong public hospitals. The survey was developed to identify key issues
pertinent to the role of nurses in managing CINV. Data were collected from the
following areas (a) demographics, (b) assessment of CINV, (c) CINV management and
(d) barriers and facilitators to good CINV practice. RESULTS: Only a third of
respondents performed a CINV assessment before starting chemotherapy, and more
than 40% reported that the use of a standardised assessment tool was uncommon.
Nearly half recognised that they had inadequate knowledge of different aspects of
CINV, but the majority could clearly state the most common pharmacological agents
used to treat chemotherapy-induced nausea (88.3%) and vomiting (87.4%). The
barriers respondents most frequently encountered in CINV prevention and
management were lack of time and a heavy workload. Adopting a standardised CINV
assessment tool and management protocol together with further professional
training were identified as the major facilitators in improving CINV prevention
and management. CONCLUSIONS: Respondents perceived their knowledge of CINV
prevention and management as inadequate. There is a need to adopt a standardised
assessment tool, to develop a management protocol and to introduce further
professional training to meet the expanding needs of both patients and nurses.
PMID- 23153453
TI - Toxicities, complications, and clinical encounters during intraperitoneal
chemotherapy in 17 women with ovarian cancer.
AB - PURPOSE OF THE RESEARCH: Intraperitoneal (IP) chemotherapy is a viable and
superior treatment to standard intravenous (IV) chemotherapy in women with small
volume residual ovarian cancer following optimal debulking. Despite this clinical
advantage, widespread adoption of the treatment regimen has been hampered by
concerns related to toxicities and complications. The purpose of this descriptive
study was to describe nursing implications related to toxicities, complications
and clinical encounters in 17 women with ovarian cancer who received IP
chemotherapy. METHODS AND SAMPLE: Women with ovarian cancer who received IP
chemotherapy at one NCI-designated comprehensive cancer center were accrued. Data
related to IP chemotherapy summary, clinical encounters and admissions were
obtained through comprehensive chart audits. KEY RESULTS: Common treatment
related toxicities included nausea and vomiting, fatigue, hypomagnesia, pain,
neuropathy, anemia, and constipation. Reasons for dose-modifications were multi
factorial, and were primarily related to catheter complications and chemotherapy
toxicities. The number of clinical encounters was high, and they were primarily
related to admissions for inpatient IP chemotherapy and follow-up clinic visits.
CONCLUSIONS: Treatment-related toxicities and complications were common in women
with ovarian cancer who received IP chemotherapy. Use of IP chemotherapy results
in multiple clinical encounters, such as outpatient clinic visits and inpatient
admissions. Nursing is a critical part of the interdisciplinary approach in
caring for women treated with IP chemotherapy. Interdisciplinary teams with high
levels of knowledge and skills related to IP chemotherapy administration are
needed to manage treatment-related toxicities and complications, and support
multiple clinical encounters during treatment.
PMID- 23153454
TI - Chromoblastomycosis caused by Fonsecaea: clinicopathology, susceptibility and
molecular identification of seven consecutive cases in Southern China.
AB - The clinicopathological and microbiological features of chromoblastomycosis
caused by Fonsecaea pedrosoi or Fonsecaea monophora are summarized. Four F.
monophora and three F. pedrosoi strains were isolated from seven consecutive
chromoblastomycosis patients and identified by genetic analysis between 2004 and
2012 in a teaching hospital in southern China. Six strains were sensitive to
voriconazole, itraconazole and terbinafine using E-test and Neo-Sensitabs. Six
patients healed after oral itraconazole or terbinafine, and one was lost to
follow up. Internal transcribed spacer sequence is sufficient for species
delimitation of Fonsecaea, and the Neo-Sensitabs test and E-test are comparable
in their susceptibility testing. Itraconazole and/or terbinafine may be the
preferred treatment for this chromoblastomycosis.
PMID- 23153456
TI - IFNalpha converts IL-22 into a cytokine efficiently activating STAT1 and its
downstream targets.
AB - Besides their antiviral activity, type I Interferons (IFN) display context
specific immunomodulation. In contrast to long-known IFNalpha/beta, Interleukin
(IL)-22 is an anti-bacterial, largely tissue protective cytokine that recently
gained attention. Herein, cellular IFNalpha/IL-22 interactions are investigated.
We report that pre-conditioning of epithelial cells with IFNalpha initiated
dramatic changes in IL-22 signaling normally dominated by signal transducer and
activator of transcription (STAT)-3. Specifically, by using human DLD1 colon
epithelial/carcinoma cells we demonstrate that, upon IFNalpha, IL-22 converts
into a cytokine robustly activating STAT1 and its downstream pro-inflammatory
targets CXCL9, CXCL10, and inducible nitric oxide synthase (iNOS). Accordingly,
only after IFNalpha pre-incubation was IL-22-induced STAT1 binding to the CXCL10
promoter detectable. Using the viral mimic polyinosinic:polycytidylic acid and
the IFNalpha/beta antagonist B18R we furthermore demonstrate the capability of
endogenous IFN to promote IL-22-induced STAT1 activation and expression of
CXCL10. IL-22-induced STAT1 activation subsequent to IFNalpha priming became
likewise apparent in human Caco2 colon epithelial/carcinoma cells, HepG2 hepatoma
cells, and primary keratinocytes. Current observations may relate to
characteristics of IFNalpha/beta in clinical therapy and expose margins of tissue
protection by IL-22 application.
PMID- 23153455
TI - Overexpression of ATP-binding cassette transporter ABCG2 as a potential mechanism
of acquired resistance to vemurafenib in BRAF(V600E) mutant cancer cells.
AB - Melanoma is the most serious type of skin cancer with a high potential for
metastasis and very low survival rates. The discovery of constitutive activation
of the BRAF kinase caused by activating BRAF(V600E) kinase mutation in most
melanoma patients led to the discovery of the first potent BRAF(V600E) signaling
inhibitor, vemurafenib. Vemurafenib was effective in treating advanced melanoma
patients and was proposed for the treatment of other BRAF(V600E) mutant cancers
as well. Unfortunately, the success of vemurafenib was hampered by the rapid
development of acquired resistance in different types of BRAF(V600E) mutant
cancer cells. It becomes important to identify and evaluate all of the potential
mechanisms of cellular resistance to vemurafenib. In this study, we characterized
the interactions of vemurafenib with three major ATP-binding cassette (ABC)
transporters, ABCB1, ABCC1 and ABCG2. We found that vemurafenib stimulated the
ATPase activity and potently inhibited drug efflux mediated by ABCB1 and ABCG2.
Vemurafenib also restored drug sensitivity in ABCG2-overexpressing cells.
Moreover, we revealed that in the presence of functional ABCG2, BRAF kinase
inhibition by vemurafenib is reduced in BRAF(V600E) mutant A375 cells. Taken
together, our findings indicate that ABCG2 confers resistance to vemurafenib in
A375 cells, suggesting involvement of this transporter in acquired resistance to
vemurafenib. Thus, combination chemotherapy targeting multiple pathways could be
an effective therapeutic strategy to overcome acquired resistance to vemurafenib
for cancers harboring the BRAF(V600E) mutation.
PMID- 23153457
TI - Estrogen receptor beta agonists affect growth and gene expression of human breast
cancer cell lines.
AB - Expression of estrogen receptor beta (ERbeta) has been described to reduce growth
of cancer cell lines derived from hormone-dependent tumors, like breast cancer.
In this study we tested to what extent two ERbeta agonists, androgen derivative
3beta-Adiol and flavonoid Liquiritigenin, would affect growth and gene expression
of different ERbeta-positive human breast cancer cell lines. Under standard cell
culture conditions, we observed 3beta-Adiol to inhibit growth of MCF-7 cells in a
dose-dependent manner, whereas growth of BT-474 and MCF-10A cells was suppressed
by the maximum concentration (100 nM) only. When treated in serum-free medium,
all cell lines except of MDA-MB-231 were responsive to 1 nM 3beta-Adiol, and ZR75
1 cells exhibited a dose-dependent antiproliferative response. Providing putative
mechanisms underlying the observed growth-inhibitory effect, expression of Ki-67
or cyclins A2 and B1 was downregulated after 3beta-Adiol treatment in all
responsive lines. In contrast, treatment with lower doses of Liquiritigenin did
not affect growth. In MCF-7 cells, the highest dose of this flavonoid exerted
proliferative effects accompanied by increased expression of cyclin B1, PR and
PS2, indicating unspecific activation of ERalpha. In conclusion, the ERbeta
agonists tested exerted distinct concentration-dependent and cell line-specific
effects on growth and gene expression. The observed inhibitory effects of 3beta
Adiol on breast cancer cell growth encourage further studies on the potential of
this and other ERbeta agonists as targeted drugs for breast cancer therapy.
PMID- 23153458
TI - Proteome-wide study of endoplasmic reticulum stress induced by thapsigargin in
N2a neuroblastoma cells.
AB - Disturbances in intraluminal endoplasmic reticulum (ER) Ca(2+) concentration
leads to the accumulation of unfolded proteins and perturbation of intracellular
Ca(2+) homeostasis, which has a huge impact on mitochondrial functioning under
normal and stress conditions and can trigger cell death. Thapsigargin (TG) is
widely used to model cellular ER stress as it is a selective and powerful
inhibitor of sarcoplasmic/endoplasmic reticulum Ca(2+) ATPases. Here we provide a
representative proteome-wide picture of ER stress induced by TG in N2a
neuroblastoma cells. Our proteomics study revealed numerous significant protein
expression changes in TG-treated N2a cell lysates analysed by two-dimensional
electrophoresis followed by mass spectrometric protein identification. The
proteomic signature supports the evidence of increased bioenergetic activity of
mitochondria as several mitochondrial enzymes with roles in ATP-production,
tricarboxylic acid cycle and other mitochondrial metabolic processes were
upregulated. In addition, the upregulation of the main ER resident proteins
confirmed the onset of ER stress during TG treatment. It has become widely
accepted that metabolic activity of mitochondria is induced in the early phases
in ER stress, which can trigger mitochondrial collapse and subsequent cell death.
Further investigations of this cellular stress response in different neuronal
model systems like N2a cells could help to elucidate several neurodegenerative
disorders in which ER stress is implicated.
PMID- 23153459
TI - Coupling microbial catabolic actions with abiotic redox processes: a new recipe
for persistent organic pollutant (POP) removal.
AB - The continuous release of toxic persistent organic pollutants (POPs) into the
environment has raised a need for effective cleanup methods. The tremendous
natural diversity of microbial catabolic mechanisms suggests that catabolic
routes may be applied to the remediation of POP-contaminated fields. A large
number of the recalcitrant xenobiotics have been shown to be removable via the
natural catabolic mechanisms of microbes, and detailed biochemical studies of the
catabolic methods, together with the development of sophisticated genetic
engineering, have led to the use of synthetic microbes for the bioremediation of
POPs. However, the steric effects of substituted halogen moieties, microbe
toxicity, and the low bioavailability of POPs still deteriorate the efficiency of
removal strategies based on natural and synthetic catabolic mechanisms. Recently,
abiotic redox processes that induce rapid reductive dehalogenation, hydroxyl
radical-based oxidation, or electron shuttling have been reasonably coupled with
microbial catabolic actions, thereby compensating for the drawbacks of biotic
processes in POP removal. In this review, we first compare the pros and cons of
individual methodologies (i.e., the natural and synthetic catabolism of microbes
and the abiotic processes involving zero-valent irons, advanced oxidation
processes, and small organic stimulants) for POP removal. We then highlight
recent trends in coupling the biotic-abiotic methodologies and discuss how the
processes are both feasible and superior to individual methodologies for POP
cleanup. Cost-effective and environmentally sustainable abiotic redox actions
could enhance the microbial bioremediation potential for POPs.
PMID- 23153460
TI - Enhancing stem cell survival in vivo for tissue repair.
AB - The ability to use progenitor cells for regenerative medicine remains an evolving
but elusive clinical goal. A serious obstacle towards widespread use of stem
cells for tissue regeneration is the challenges that face these cells when they
are placed in vivo into a wound for therapy. These environments are hypoxic,
acidic, and have an upregulation of inflammatory mediators creating a region that
is hostile towards cellular survival. Within this environment, the majority of
progenitor cells undergo apoptosis prior to participating in lineage
differentiation and cellular integration. In order to maximize the clinical
utility of stem cells, strategies must be employed to increase the cell's ability
to survive in vivo through manipulation of both the stem cell and the surrounding
environment. This review focuses on current advances and techniques being used to
increase in vivo stem cell survival for the purpose of tissue regeneration.
PMID- 23153461
TI - [Audiological care should be reformed].
PMID- 23153462
TI - [Acute medical coordination dispatch centres will be key partners, allowing more
people to survive out-of-hospital cardiac arrests].
PMID- 23153463
TI - [Renewal of a hearing aid is a medical task].
AB - A 67 year-old man was known to have a right-sided hearing loss with a normal
discrimination score (DS) and was treated with a hearing aid (HA) in the right
ear. An MRI-scan was normal. In 2006 and 2010 the HA was renewed at a private
hearing aid clinic. No DS was performed. At the audiology clinic we found a
masked DS of 0% and progression of the hearing loss. An MRI-scan revealed a
vestibular schwannoma (VS) on the right side. The patient was fitted with an HA
in the left ear and MRI-scans every six months. A masked DS could have revealed
the VS and correct treatment thus could have been initiated sooner.
PMID- 23153464
TI - [Vestibular schwannoma as cause of sudden unilateral deafness and tinnitus].
AB - Vestibular schwannoma (VS) is a rare disorder. In Denmark, approximately 120
patients are being diagnosed yearly. This is a case report of a 29-year-old
female patient with VS, which began with sudden deafness 6-7 years ago. The
correct diagnosis was made relatively late.
PMID- 23153465
TI - [Health professional operators at dispatch centres shall ensure identification of
cardiac arrest and initiate counselling by telephone].
AB - Denmark has introduced health professional operators (HPO) at the dispatch
centres to ensure early identification of cardiac arrest and earlier initiation
of cardiopulmonary resuscitation (CPR) to improve survival. Communicative skills
and personal competences are important, and the HPOs' medical background will
probably lead to better triage of patients. Their use of a protocol, leads to a
more frequent recognition of cardiac arrest and contributes to better CPR
guidance. A common national training for all the HPOs' has been implemented and
future guidance might include video-transmission.
PMID- 23153466
TI - [Pilonidal disease is a benign condition].
AB - Malignant transformation in pilonidal disease is rare and never reported in
Denmark. There are 75 cases in the literature, mostly squamous cell carcinoma.
The cost-benefit of routine histological examination of specimens from pilonidal
surgery is questionable, as malignancy is extremely rare. Due to increased
incidence of cancer, specimens from patients with many years of pilonidal
disease, known immunodeficiencies and/or human papillomavirus infection or
clinical abnormal presentation, should always be investigated.
PMID- 23153467
TI - [Characteristics, diagnosis and therapy of patients with autoimmune hepatitis].
AB - Autoimmune hepatitis is a relatively rare disease that may lead to rapidly
progressing liver cirrhosis and even fulminant liver failure, if diagnosis and
treatment is delayed or ineffective. Diagnosing the disease can be challenging,
and one in five patients respond insufficiently to standard treatment. Patients,
who are diagnosed late in the disease course or only respond partly to medical
treatment, are at high risk of developing severe liver insufficiency. This
article summarizes the present knowledge and evidence regarding diagnostics,
therapy and disease course.
PMID- 23153468
TI - [Mirtazapine versus other antidepressive agents for depression].
AB - A Cochrane analysis compared efficacy and side effects of mirtazapine with other
antidepressants. After six weeks of treatment no reliable difference of efficacy
between mirtazapine, selective serotonin reuptake inhibitors (SSRI),
noradrenaline reuptake inhibitors or tricyclic antidepressants was found. The
side effects like increased sleep and weight gain were compared by treatment with
mirtazapine and treatment with SSRI antidepressants. The very fact of the sleep
effect and the fast onset of action have probably increased the effect size
compared with SSRI antidepressants. The results of the Cochrane analysis cannot
for certain be generalized to inpatients, as other studies have found tricyclic
antidepressants to be especially effective.
PMID- 23153469
TI - [Family occurrence of steroid-sensitive idiopathic nephrotic syndrome].
AB - Nephrotic syndrome (NS) presented within three weeks in siblings aged six and ten
years. Both children experienced proteinuria, hypoalbuminaemia and oedema, with
the most pronounced symptoms in the older. Standard treatment with prednisolone
led to remission of the nephrotic syndrome in the younger, whereas the older
required additional therapy with tacrolismus before remission. In view of the low
incidence of NS in children, a near simultaneously onset in two siblings must
lead to genetic elucidation. Genetic disorders and other causes of childhood NS
are discussed.
PMID- 23153470
TI - [Bullectomy of giant bullae gave significant improvement of lung function].
AB - A 49-year-old male smoker experienced acute deterioration of a progressive
breathlessness. Spontaneous pneumothorax was diagnosed, and drainage was applied.
Subsequent computed tomography revealed severe bilateral emphysematous bullae
with right-sided predominance, and basal atelectasis. A lung function test showed
severe obstructive disease. Right-sided bullectomy was performed through anterior
thoracotomy with removal of giant bullae. Postoperative examination revealed
markedly improved lung function and expansion of right-sided, previously
consolidated lung tissue.
PMID- 23153471
TI - Subcutaneous phaeohyphomycosis due to Curvularia lunata in a renal transplant
patient.
AB - BACKGROUND: Phaeohyphomycosis is defined as an infection caused by melanized
fungi. It predominates in tropical climate and is currently classified as
superficial, allergic, central nervous system or lung infections, and
disseminated. Curvularia is one of the many genres which can cause this disease.
Phialophora, Alternaria and Exophiala are more commonly isolated from
subcutaneous lesions. CASE REPORT: A 25-year-old male, renal transplant recipient
presents with an ulcer on his left leg. Subcutaneous phaeohyphomycosis due to
Curvularia lunata was diagnosed based on mycological examination and
histopathological findings. He was successfully treated with systemic
itraconazole and surgical resection. CONCLUSION: The incidence of
phaeohyphomycosis has increased in the last decades, especially in
immunosuppressed individuals; nevertheless the number of cases does not allow for
therapeutic controlled trials to be performed. Hence, we consider that it is
important to communicate individual cases and reviews of the literature, to
increase awareness of the disease, its clinical presentation and response to
treatment.
PMID- 23153472
TI - Acupuncture in the treatment of obesity: a narrative review of the literature.
AB - Obesity is one of the leading health risk factors worldwide and is associated
with several other risk factors and health problems including type 2 diabetes
mellitus, cardiovascular disease and malignancies. Current conventional
therapeutic strategies for obesity cannot achieve adequate weight control in all
patients, so complementary types of treatment are also performed. Acupuncture,
one of the oldest healing practices, represents the most rapidly growing
complementary therapy which is recognised by both the National Institutes of
Health and the WHO. A previous review concluded that acupuncture was superior to
lifestyle advice, to sham acupuncture and to conventional medication. In this
narrative review, the possible mechanisms of actions and the results of recent
experimental and clinical studies with different forms of acupuncture (eg, body,
auricular, manual and electroacupuncture) are presented. In particular, the
effects of acupuncture on anorexigenic and orexigenic peptides, insulin
resistance, lipid metabolism and inflammatory markers are discussed. Both
experimental and clinical current data suggest that acupuncture exerts beneficial
effects on the mechanisms of obesity. Some data suggest that electroacupuncture
may be more effective than manual acupuncture; however, the most effective
frequency remains controversial. Combination of different forms of acupuncture
with diet and exercise seems to be necessary for achieving and maintaining weight
loss. Further prospective clinical trials are needed to establish the
effectiveness of this complementary method for obesity treatment.
PMID- 23153473
TI - Ongoing outbreak of an acute muscular Sarcocystis-like illness among travellers
returning from Tioman Island, Malaysia, 2011-2012.
AB - As of 4 November, 2012, 100 patients with an acute muscular Sarcocystis-like
illness associated with travel to Tioman Island, Malaysia, have been identified.
Thirty-five travelled there mostly during July and August 2011 and 65 mostly
during July and August 2012, suggesting an ongoing outbreak. Epidemiological
investigations are ongoing. Public health agencies and practicing clinicians
should be aware of this rarely-reported disease in humans and consider it as
differential diagnosis in travellers returning from Tioman Island.
PMID- 23153474
TI - Recurrent pyelonephritis due to NDM-1 metallo-beta-lactamase producing
Pseudomonas aeruginosa in a patient returning from Serbia, France, 2012.
AB - We describe the first isolation in France of a New-Delhi metallo-beta-lactamase-1
(NDM-1) producing Pseudomonas aeruginosa. In March 2012, a patient with history
of prior hospitalisation in Serbia was diagnosed in France with acute
pyelonephritis due to NDM-1 producing P. aeruginosa. Clinical and microbiological
cure was obtained under appropriate antibiotic treatment. Two months later, she
presented with a recurrence due to the same bacteria, with a favourable
evolution. During both hospitalisations, contact isolation precautions were
implemented and no cross-transmission was observed.
PMID- 23153475
TI - Hospitalisation associated with the 2009 H1N1 pandemic and seasonal influenza in
Hong Kong, 2005 to 2010.
AB - Reliable estimates of the morbidity burden caused by the 2009 pandemic influenza
(pH1N1) are important for assessing the severity of the pandemic. Poisson
regression models were fitted to weekly numbers of cause-specific hospitalisation
in Hong Kong from 2005 to 2010. Excess hospitalisation associated with the 2009
pandemic and seasonal influenza was derived from the model by incorporating the
proxy variables of weekly proportions of specimens positive for the pandemic
influenza A(H1N1)pdm09, seasonal influenza A (subtypes H3N2 and H1N1) and B
viruses. Compared with seasonal influenza, pH1N1 influenza was associated with
higher hospitalisation rates for acute respiratory disease (ARD) among children
younger than 18 years and adults aged between 18 and 64 years, but among the
elderly aged 65 years and older the hospitalisation rates were lower for pH1N1
than for seasonal H3N2 and H1N1 influenza. Hospitalisation rates for chronic
diseases associated with pH1N1 influenza were generally higher than those
associated with seasonal influenza. The reported hospitalised cases with
laboratory-confirmed pandemic infections accounted for only 16% of pH1N1
influenza-associated hospitalisations for ARD in the age group 75 years and
older, and 5-66% of hospitalisations for chronic diseases in those older than 40
years. The 2009 H1N1 influenza pandemic was associated with a dramatically
increased risk of hospitalisation among children and young adults. The morbidity
burden of pandemic was underreported in old people and in those with chronic
conditions.
PMID- 23153476
TI - Assessment of the bio-preparedness and of the training of the French hospital
laboratories in the event of biological threat.
AB - A national laboratory network 'Biotox-Piratox' was created in 2003 in France with
the purpose of detecting, confirming and reporting potential biological and
chemical threat agents. This network is divided into three levels: Level 1 is
dedicated to the evaluation of risks (biological, chemical, radiological), to
sampling and packing. Level 2 consists of university and military hospitals, who
deal with biological specimens, and of environmental and veterinary laboratories,
who deal with environmental and animal samples. Level 3 comprises national
reference laboratories and the Jean Merieux biosafety level (BSL)-4 laboratory in
Lyon. This report presents the results of four bio-preparedness exercises to
check critical points in the processing of samples. These exercises took place in
2007, 2009, 2010 and 2011. Each of them consisted of two parts. The first part
was the identification of an unknown bacterial strain and its susceptibility to
antibiotics used as a default in case of a bioterrorist event. The second part
was the detection of Class III microorganisms, mainly by molecular techniques.
The main lesson learnt in these exercises was that the key to successful
detection of biological agents in case of a biological threat was standardisation
and validation of the methods implemented by all the laboratories belonging to
the network.
PMID- 23153477
TI - Pre-cachexia and cachexia at diagnosis of stage III non-small-cell lung
carcinoma: an exploratory study comparing two consensus-based frameworks.
AB - Despite the development of consensus-based frameworks to define cancer cachexia,
the validity and usefulness of these frameworks are relatively unknown. The aim
of the present study was to study the presence of pre-cachexia and cachexia in
patients with stage III nonsmall-cell lung carcinoma (NSCLC) by using a cancer
specific framework and a general framework for cachexia, and to explore the
prognostic value of pre-cachexia and cachexia. In forty patients at diagnosis of
stage III NSCLC, weight loss, fat-free mass, handgrip strength, anorexia and
serum biochemistry, assessed before the first chemotherapy, were used to define
'cancer cachexia' or 'cachexia'. The cancer-specific framework also classified
for pre-cachexia and refractory cachexia. Additionally, quality of life was
assessed by the European Organisation for Research and Treatment of Cancer
Quality of Life Questionnaire C30. Groups were compared using independent t
tests, ANOVA, Kaplan-Meier and Cox survival analyses. Based on the cancer
specific framework, pre-cachexia was present in nine patients (23%) and cancer
cachexia was present in seven patients (18%). Cancer cachexia was associated with
a reduced quality of life (P = 0.03) and shorter survival (hazard ratio (HR) =
2.9; P = 0.04). When using the general framework, cachexia was present in eleven
patients (28%), and was associated with a reduced quality of life (P = 0.08) and
shorter survival (HR = 4.4; P = 0.001). In conclusion, pre-cachexia and cachexia
are prevalent in this small population of patients at diagnosis of stage III
NSCLC. For both frameworks, cachexia appears to be associated with a reduced
quality of life and shorter survival. Further studies are warranted to more
extensively explore the validity and prognostic value of these new frameworks in
cancer patients.
PMID- 23153478
TI - Diet-induced antisecretory factor prevents intracranial hypertension in a dosage
dependent manner.
AB - Intake of specially processed cereal (SPC) stimulates endogenous antisecretory
factor (AF) activity, and SPC intake has proven to be beneficial for a number of
clinical conditions. The aim of the present study was to investigate the dosage
relationship between SPC intake and plasma AF activity and to further correlate
achieved AF levels to a biological effect. SPC was fed to rats in concentrations
of 5, 10 or 15% for 2 weeks. A further group was fed 5% SPC for 4 weeks. AF
activity and the complement factors C3c and factor H were analysed in plasma
after the feeding period. Groups of rats fed the various SPC concentrations were
subjected to a standardised freezing brain injury, known to induce increases in
intracranial pressure (ICP). The AF activity in plasma increased after intake of
SPC, in a dosage- and time-dependent manner. The complement factors C3c and
factor H increased in a time-dependent manner. Measurements of ICP in animals fed
with SPC prior to the brain injury showed that the ICP was significantly lower,
compared with that of injured rats fed with a standard feed, and that the change
was dose and time dependent. AF activity increases, in a dosage- and time
dependent manner, after intake of SPC. The inverse relationship between ICP after
a head injury and the percentage of SPC in the feed indicate that the protective
effect is, to a large extent, due to AF.
PMID- 23153480
TI - Statement regarding the pre and post market assessment of durable, implantable
ventricular assist devices in the United States: executive summary.
AB - The incorporation of complex medical device technologies into clinical practice
is governed by critical oversight of the US Food and Drug Administration. This
regulatory process requires a judicious balance between assuring safety and
efficacy, while providing efficient review to facilitate access to innovative
therapies. Recent contrasting views of the regulatory process have emphasized the
difficulties in obtaining an optimal balance. Mechanical circulatory support has
evolved to become an important therapy for patients with advanced heart failure
with the advent of more durable, implantable ventricular assist devices. The
regulatory oversight of these new technologies has been difficult owing to the
complexities of these devices, associated adverse event profile, and severity of
illness of the intended patient population. Maintaining a regulatory environment
to foster efficient introduction of safe and effective technologies is critical
to the success of ventricular assist device therapy and the health of patients
with advanced heart failure. Physicians representing key surgical and cardiology
societies, and representatives from the Food and Drug Administration, National
Heart Lung, and Blood Institute, Centers for Medicare and Medicaid Services,
Interagency Registry of Mechanically Assisted Circulatory Support, and industry
partners gathered to discuss relevant issues regarding the current regulatory
environment assessing ventricular assist devices. The goal of the meeting was to
explore innovative ways to foster the introduction of technologically advanced,
safe, and effective ventricular assist devices. The following summary reflects
opinions and conclusions endorsed by The Society of Thoracic Surgeons, American
Association for Thoracic Surgery, American Heart Association, Heart Failure
Society of America, International Society for Heart and Lung Transplantation, and
the Interagency Registry of Mechanically Assisted Circulatory Support.
PMID- 23153481
TI - Statement regarding the pre and post market assessment of durable, implantable
ventricular assist devices in the United States.
AB - The incorporation of complex medical device technologies into clinical practice
is governed by critical oversight of the US Food and Drug Administration. This
regulatory process requires a judicious balance between assuring safety and
efficacy, while providing efficient review to facilitate access to innovative
therapies. Recent contrasting views of the regulatory process have emphasized the
difficulties in obtaining an optimal balance. Mechanical circulatory support has
evolved to become an important therapy for patients who have advanced heart
failure with the advent of more durable, implantable ventricular assist devices.
The regulatory oversight of these new technologies has been difficult owing to
the complexities of these devices, associated adverse event profile, and severity
of illness of the intended patient population. Maintaining a regulatory
environment to foster efficient introduction of safe and effective technologies
is critical to the success of ventricular assist device therapy and the health of
patients with advanced heart failure. Physicians representing key surgical and
cardiology societies, and representatives from the Food and Drug Administration,
National Heart Lung, and Blood Institute, Centers for Medicare and Medicaid
Services, Interagency Registry of Mechanically Assisted Circulatory Support, and
industry partners gathered to discuss relevant issues regarding the current
regulatory environment assessing ventricular assist devices. The goal of the
meeting was to explore innovative ways to foster the introduction of
technologically advanced, safe, and effective ventricular assist devices. The
following summary reflects opinions and conclusions endorsed by The Society of
Thoracic Surgeons, American Association for Thoracic Surgery, American Heart
Association, Heart Failure Society of America, International Society for Heart
and Lung Transplantation, and Interagency Registry of Mechanically Assisted
Circulatory Support.
PMID- 23153482
TI - Neuropsychological profiles of children with aqueductal stenosis and Spina Bifida
myelomeningocele.
AB - We compared neuropsychological profiles in children with shunted hydrocephalus
secondary to aqueductal stenosis (AS), a rare form of congenital hydrocephalus,
and spina bifida myelomeningocele (SBM), a common form of congenital
hydrocephalus. Participants were 180 children with shunted hydrocephalus grouped
according to etiology: SBM (n = 151), AS (n = 29), and typically developing (TD;
n = 60) individuals. The group with AS performed below the TD group on all tasks
except for reading, and their overall performance was higher than the group with
SBM, who had the lowest performance in the sample. Both clinical groups
significantly differed from the TD group on tasks of spatial function, concept
formation, motor function, and memory. Performance of the subgroup of AS children
with normal cerebellum status approximated that of the TD group, while those with
cerebellar anomalies performed lower than others with AS. Cerebellar
abnormalities (present in the whole SBM group and in a subset of the AD group)
are associated with more compromise of cognitive as well as motor function.
PMID- 23153483
TI - Quality control and fidelity.
PMID- 23153485
TI - Curvature, lipid packing, and electrostatics of membrane organelles: defining
cellular territories in determining specificity.
AB - Whereas some rare lipids contribute to the identity of cell organelles, we focus
on the abundant lipids that form the matrix of organelle membranes. Observations
using bioprobes and peripheral proteins, notably sensors of membrane curvature,
support the prediction that the cell contains two broad membrane territories: the
territory of loose lipid packing, where cytosolic proteins take advantage of
membrane defects, and the territory of electrostatics, where proteins are
attracted by negatively charged lipids. The contrasting features of these
territories provide specificity for reactions occurring along the secretory
pathway, on the plasma membrane, and also on lipid droplets and autophagosomes.
PMID- 23153484
TI - Building complexity: insights into self-organized assembly of microtubule-based
architectures.
AB - Successful completion of diverse cellular functions, such as mitosis, positioning
organelles, and assembling cilia, depends on the proper assembly of microtubule
based structures. While essentially all of the proteins needed to assemble these
structures are now known, we cannot explain how even simple features such as size
and shape are determined. As steps toward filling this knowledge gap, there have
been several recent efforts toward reconstituting, with purified proteins, the
basic structural motifs that recur in diverse cytoskeletal arrays. We discuss
these studies and highlight how they shed light on the self-organized assembly of
complex and dynamic cytoskeleton-based cellular structures.
PMID- 23153486
TI - Design principles of protein biosynthesis-coupled quality control.
AB - The protein biosynthetic machinery, composed of ribosomes, chaperones, and
localization factors, is increasingly found to interact directly with factors
dedicated to protein degradation. The coupling of these two opposing processes
facilitates quality control of nascent polypeptides at each stage of their
maturation. Sequential checkpoints maximize the overall fidelity of protein
maturation, minimize the exposure of defective products to the bulk cellular
environment, and protect organisms from protein misfolding diseases.
PMID- 23153487
TI - Chromothripsis: chromosomes in crisis.
AB - During oncogenesis, cells acquire multiple genetic alterations that confer
essential tumor-specific traits, including immortalization, escape from
antimitogenic signaling, neovascularization, invasiveness, and metastatic
potential. In most instances, these alterations are thought to arise
incrementally over years, if not decades. However, recent progress in sequencing
cancer genomes has begun to challenge this paradigm, because a radically
different phenomenon, termed chromothripsis, has been suggested to cause complex
intra- and interchromosomal rearrangements on short timescales. In this Review,
we review established pathways crucial for genome integrity and discuss how their
dysfunction could precipitate widespread chromosome breakage and rearrangement in
the course of malignancy.
PMID- 23153488
TI - Silencing by throwing away: a role for chromatin diminution.
AB - Chromatin diminution during development generates cells with varying genetic
content within the same organism. Two recent papers demonstrate that in two
different systems chromatin diminution removes a considerable number of genes
from somatic cells, thereby restricting their expression to the germline.
PMID- 23153489
TI - A new direction for gene looping.
AB - Upon binding to a promoter, RNA polymerase II can synthesize either a coding mRNA
or a divergently transcribed noncoding RNA. In a recent issue of Science, Tan
Wong et al. (2012) find that intragenic looping increases the proper orientation
of RNA polymerase II, reducing the production of divergent noncoding transcripts.
PMID- 23153490
TI - IRE1, a double-edged sword in pre-miRNA slicing and cell death.
AB - IRE1alpha, the most conserved transducer of the unfolded protein response, plays
critical roles in many biological processes and cell fate decisions. Reporting in
Science, Upton et al. (2012) broadened our understanding of IRE1alpha as a cell
death executioner, showing that upon ER stress, IRE1alpha degrades microRNAs to
promote translation of caspase-2.
PMID- 23153491
TI - Choreographing the axo-dendritic dance.
AB - The assembly of neuronal synapses in the brain relies on a sophisticated
bidirectional signal exchange between synaptic partners. In a recent issue of
Neuron, Ito-Ishida and colleagues (2012) uncover a morphogenetic program
underlying the formation of presynaptic terminals.
PMID- 23153492
TI - Arl13b in primary cilia regulates the migration and placement of interneurons in
the developing cerebral cortex.
AB - Coordinated migration and placement of interneurons and projection neurons lead
to functional connectivity in the cerebral cortex; defective neuronal migration
and the resultant connectivity changes underlie the cognitive defects in a
spectrum of neurological disorders. Here we show that primary cilia play a
guiding role in the migration and placement of postmitotic interneurons in the
developing cerebral cortex and that this process requires the ciliary protein,
Arl13b. Through live imaging of interneuronal cilia, we show that migrating
interneurons display highly dynamic primary cilia and we correlate cilia dynamics
with the interneuron's migratory state. We demonstrate that the guidance cue
receptors essential for interneuronal migration localize to interneuronal primary
cilia, but their concentration and dynamics are altered in the absence of Arl13b.
Expression of Arl13b variants known to cause Joubert syndrome induce defective
interneuronal migration, suggesting that defects in cilia-dependent interneuron
migration may in part underlie the neurological defects in Joubert syndrome
patients.
PMID- 23153493
TI - Anisotropy of Crumbs and aPKC drives myosin cable assembly during tube formation.
AB - The formation of tubular structures from epithelial sheets is a key process of
organ formation in all animals, but the cytoskeletal rearrangements that cause
the cell shape changes that drive tubulogenesis are not well understood. Using
live imaging and super-resolution microscopy to analyze the tubulogenesis of the
Drosophila salivary glands, I find that an anisotropic plasma membrane
distribution of the protein Crumbs, mediated by its large extracellular domain,
determines the subcellular localization of a supracellular actomyosin cable in
the cells at the placode border, with myosin II accumulating at edges where
Crumbs is lowest. Laser ablation shows that the cable is under increased tension,
implying an active involvement in the invagination process. Crumbs anisotropy
leads to anisotropic distribution of aPKC, which in turn can negatively regulate
Rok, thus preventing the formation of a cable where Crumbs and aPKC are
localized.
PMID- 23153494
TI - The NF-kappaB signaling protein Bcl10 regulates actin dynamics by controlling AP1
and OCRL-bearing vesicles.
AB - The protein Bcl10 contributes to adaptive and innate immunity through the
assembly of a signaling complex that plays a key role in antigen receptor and FcR
induced NF-kappaB activation. Here we demonstrate that Bcl10 has an NF-kappaB
independent role in actin and membrane remodeling downstream of FcR in human
macrophages. Depletion of Bcl10 impaired Rac1 and PI3K activation and led to an
abortive phagocytic cup rich in PI(4,5)P(2), Cdc42, and F-actin, which could be
rescued with low doses of F-actin depolymerizing drugs. Unexpectedly, we found
Bcl10 in a complex with the clathrin adaptors AP1 and EpsinR. In particular,
Bcl10 was required to locally deliver the vesicular OCRL phosphatase that
regulates PI(4,5)P(2) and F-actin turnover, both crucial for the completion of
phagosome closure. Thus, we identify Bcl10 as an early coordinator of NF-kappaB
mediated immune response with endosomal trafficking and signaling to F-actin
remodeling.
PMID- 23153495
TI - Sox2 in the dermal papilla niche controls hair growth by fine-tuning BMP
signaling in differentiating hair shaft progenitors.
AB - How dermal papilla (DP) niche cells regulate hair follicle progenitors to control
hair growth remains unclear. Using Tbx18(Cre) to target embryonic DP precursors,
we ablate the transcription factor Sox2 early and efficiently, resulting in
diminished hair shaft outgrowth. We find that DP niche expression of Sox2
controls the migration speed of differentiating hair shaft progenitors.
Transcriptional profiling of Sox2 null DPs reveals increased Bmp6 and decreased
BMP inhibitor Sostdc1, a direct Sox2 transcriptional target. Subsequently, we
identify upregulated BMP signaling in knockout hair shaft progenitors and
demonstrate that Bmp6 inhibits cell migration, an effect that can be attenuated
by Sostdc1. A shorter and Sox2-negative hair type lacks Sostdc1 in the DP and
shows reduced migration and increased BMP activity of hair shaft progenitors.
Collectively, our data identify Sox2 as a key regulator of hair growth that
controls progenitor migration by fine-tuning BMP-mediated mesenchymal-epithelial
crosstalk.
PMID- 23153496
TI - Single-cell-resolution imaging of the impact of Notch signaling and mitosis on
segmentation clock dynamics.
AB - Vertebrate body segmentation is controlled by the segmentation clock, a molecular
oscillator involving transcriptional oscillations of cyclic genes in presomitic
mesoderm cells. The rapid and highly dynamic nature of this oscillating system
has proved challenging for study at the single-cell level. We achieved
visualization of clock activity with a cellular level of resolution in living
embryos, allowing direct comparison of oscillations in neighbor cells. We provide
direct evidence that presomitic mesoderm cells oscillate asynchronously in
zebrafish Notch pathway mutants. By tracking oscillations in mitotic cells, we
reveal that a robust cell-autonomous, Notch-independent mechanism resumes
oscillations after mitosis. Finally, we find that cells preferentially divide at
a certain oscillation phase, likely reducing the noise generated by cell division
in cell synchrony and suggesting an intriguing relationship between the mitotic
cycle and clock oscillation.
PMID- 23153497
TI - Mechanistic differences in the transcriptional interpretation of local and long
range Shh morphogen signaling.
AB - Morphogens orchestrate tissue patterning in a concentration-dependent fashion
during vertebrate embryogenesis, yet little is known of how positional
information provided by such signals is translated into discrete transcriptional
outputs. Here we have identified and characterized cis-regulatory modules (CRMs)
of genes operating downstream of graded Shh signaling and bifunctional Gli
proteins in neural patterning. Unexpectedly, we find that Gli activators have a
noninstructive role in long-range patterning and cooperate with SoxB1 proteins to
facilitate a largely concentration-independent mode of gene activation. Instead,
the opposing Gli-repressor gradient is interpreted at transcriptional levels,
and, together with CRM-specific repressive input of homeodomain proteins,
comprises a repressive network that translates graded Shh signaling into regional
gene expression patterns. Moreover, local and long-range interpretation of Shh
signaling differs with respect to CRM context sensitivity and Gli-activator
dependence, and we propose that these differences provide insight into how
morphogen function may have mechanistically evolved from an initially binary
inductive event.
PMID- 23153498
TI - [Paralysing lumbar disc herniation: a surgical emergency? Reflexion about a
series of 24 patients and literature data].
AB - BACKGROUND AND PURPOSE: Paralysing lumbar disc herniation (LDH): what and when to
do? Few studies have analyzed the optimal timing of surgery in case of paralysing
LDH. METHODS: Twenty-four charts were retrospectively reviewed of patients
suffering of LDH with severe motor deficit. RESULTS: There were 16 men and eight
women. Mean age was 45.1 years. Seventeen patients suffered of lumbar pain, 15 of
radicular pain and all of a severe motor deficit, implying mostly the ankle
flexion (17 patients). LDH was most frequently located at L4/L5 or L5/S1 level.
Surgery was proposed to all patients at the end of the consultation. Nine
patients were operated within 48 hours. The mean interval between onset of motor
deficit and operation was 20 days. The statistical analysis did not reveal any
significant difference among different prognostic factors between the 17 patients
with good motor recovery and the seven patients with poor motor recovery. In
particular the operative delay did not appear to influence the degree of motor
recovery. Literature review on paralysing LDH provides five published series
since 1996, including 28 to 116 patients. Two series, including the single
prospective one, conclude that the degree of recovery of motor function is
inversely related to the degree and duration of motor deficit. CONCLUSIONS: Our
retrospective series of 24 operated paralysing LDH did not reveal any prognostic
factor for motor recovery. There is no evidence based medicine data in the
literature about the optimal timing of decompressive surgery. A relative
consensus exists among spine surgeons for paralysing LDH: since operative
indication is obvious, surgery should be done as soon as possible.
PMID- 23153499
TI - (234)U/(238)U signatures associated with uranium ore bodies: part 1 Ranger 3.
AB - The Ranger 3 ore body is an early Proterozoic U ore body in the Alligator Rivers
U province, Northern Territory, Australia. It has surface expression with a redox
front located between 30 and 50 m below the surface. The ground water U
concentration and (234)U/(238)U AR signature in the top 10 m of the weathered
zone are reported for 357 samples collected over 4 wet seasons, at 5 depths,
along a transect in-line with the hydraulic gradient and along the centre line of
the ore body and its associated dispersion halo. The results show that the
weathered zone displays a general U isotope feature for this type of ore body
with the (234)U/(238)U AR for the ground water and amorphous phase of the solid
matrix being less than 1. The ground water (234)U/(238)U AR is independent of the
annual monsoonal climate and depth within the range surface to 10 m. In the
vicinity of the U ore body the ground water (234)U/(238)U AR is 0.75 and is very
similar to the (234)U/(238)U AR of the amorphous phase of the solid (0.76). The
(234)U/(238)U ARs of the amorphous phase and ground water rise and separate to
values of 0.88 and 1.02 at the end of the transect. The rise and separation in
(234)U/(238)U AR are interpreted as evidence that the source of the U in the
ground water is from the water-soluble sub-phase of the amorphous phase and that
the ground water flow is too fast to allow the processes occurring across the
solid-water interface to reach chemical equilibrium. The data set is a robust
characterisation of the coarse and fine detail of the (234)U/(238)U AR signature
in the weathered zone of U ore bodies.
PMID- 23153500
TI - NR5A1 (SF-1) gene variants in a group of 26 young women with XX primary ovarian
insufficiency.
AB - OBJECTIVE: To determine whether NR5A1 (SF-1) variants are a cause of primary
ovarian insufficiency (POI) in 26 young women with similar genetic background.
DESIGN: Genetic and functional mutation study. SETTING: University hospitals.
PATIENT(S): Genetic analysis of the NR5A1 gene in 26 XX girls with POI.
INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): NR5A1 molecular and functional
analysis. RESULT(S): Genetic analysis revealed a new c.763C>T (p.Arg255Cys)
mutation and a recurrent c.437G>C (p.Gly146Ala) variant. Functional analysis of
the p.Arg255Cys mutant showed a marked decrease in transactivation on the Cyp11a1
and Amh promoters. The p.Gly146Ala variant was identified significantly more
often in the patients (46.1%) than in ancestry-matched control subjects (10%).
CONCLUSION(S): We identified one new NR5A1 mutation in a patient of our POI
cohort (prevalence 3.8%). Moreover, although our study is limited in the number
of cases, we report the high frequency of the p.Gly146Ala variant in this cohort
compared with the ancestry-matched control subjects. This work highlights the
important role of SF-1 in ovarian function.
PMID- 23153501
TI - Review: Transport across the placenta of mice and women.
AB - Since the advent of technologies to produce genetic knockout and transgenic mice,
the number of mouse strains suggested to be useful as models for pregnancy
related complications in the human has risen substantially. Some of these share
features in common with fetal growth restriction (FGR) and preeclampsia (PE) and
could be useful for investigating aetiologies and for testing potential
therapeutics to improve outcome in these diseases. However, since placental
pathology is a major underlying factor in both FGR and PE, it is important to
understand the similarities and differences in structure and function of the
placenta between mice and women. The main aim of this review is to directly
compare placental exchange physiology between human and mouse. The review will
compare human and mouse in both normal and pathological circumstances, to attempt
to answer the question of whether placental studies in the mouse can be
translated to the human. The review includes descriptions of placental structure
between the species, comparisons of nutrient transport, including amino acids,
glucose and calcium, and evidence of how these transport systems are altered in
both human FGR and mouse models of this disease. Finally, our review will
conclude by examining studies in which mouse models of FGR/PE have been treated
with drugs of potential therapeutic value in women and consider whether data
obtained in mice can be a prelude for clinical trials in human.
PMID- 23153502
TI - The ciliary pocket.
AB - Cilia are fascinating highly conserved organelles shared by very different
organisms from unicellular eukaryotes to vertebrates where they are involved in
motility and sensory functions. In vertebrates, the function of the primary
cilium, a unique nonmotile cilium found at the surface of most cell types during
development, remained mysterious during 40 years until its crucial function in
the control of key signaling cascades during development and its involvement in
complex genetic disorders now called ciliopathies were uncovered. Recent studies
have focused on a specific membrane domain found at the base of primary cilia in
most cell types which was already mentioned in the first descriptions of these
cilia but did not raise much interest during 50 years. This membrane domain, the
'ciliary pocket', also found at the base of some motile cilia, may act as a
platform for cilia-associated vesicular trafficking and as an interface with the
actin cytoskeleton but also likely in additional important functions which remain
to be discovered.
PMID- 23153503
TI - Enhanced gemcitabine-mediated cell killing of human lung adenocarcinoma by vector
based RNA interference against PLK1.
AB - Specific PLK1 silencing may be an effective gene therapy modality of treating
PLK1-overexpressed cancers. In this study, we first explored the anticancer
efficacy of three different short hairpin-expressing plasmids targeting PLK1 in
animal model, and then determined the combination therapy effect of gemcitabine
with PLK1-shRNA as an adjuvant. Transfection of the PLK1-shRNAs to A549 lung
cancer cells induced significant PLK1 depletion, growth inhibition and apoptosis.
In vivo administration of PLK1-shRNA constructs to tumor-bearing mice resulted in
xenograft regression. Moreover, the combination of PLK1-shRNA plus low-dose
gemcitabine (GEM) produced an additive antitumor activity on the lung tumors
owing to an inhibition of cancer cell survival and augmented apoptosis. These
results indicated a feasible bio-chemotherapeutic strategy for cancer.
PMID- 23153504
TI - Towards a "Lyon molecular signature" to individualize the treatment of rectal
cancer. Prognostic analysis of a prospective cohort of 94 rectal cancers T1-2-3
Nx MO to be the basis of a molecular signature.
AB - PURPOSE: In 1998 a translational research was initiated in Lyon aiming at
identifying a prognostic "biomolecular signature" in rectal cancer. This paper
presents the clinical outcome of the patients included in this study. PATIENTS
AND METHODS: A total of 94 patients were included between 1998 and 2001. A
staging with rectoscopy and biopsies was performed before treatment. In case of
surgery, the operative specimen was analysed to evaluate the pathological
response. There were two types of treatment: neoadjuvant radiotherapy (with or
without concurrent chemotherapy) followed by surgery (76 cases) and radiotherapy
alone with 'contactherapy' often associated with external beam radiotherapy (18
patients). RESULTS: The patients had a mean age of 63years. Stage was T1: 4, T2:
24, T3: 65 and T4: 1. The overall survival of the 94 patients was 62% at 8years
with a rate of distant metastases of 29%. Rate of local recurrence at 8years was
6% in the neoadjuvant group and 16% in the radiotherapy group with an overall
8years survival in both groups respectively: 64% and 53%. There was a trend
towards more metastases in cT3, tumour diameter above 4cm, circumferential
extension. There was a significant increase in the risk of metastases for ypT3,
ypN1-2 and Dworak score 1-2-3. In multivariate analysis ypT3 was significantly
associated with a high rate of metastases (55%; P=0.0003). CONCLUSION: The rate
of distant metastases is a major prognostic factor. These clinical results will
serve as the base line to identify a "biomolecular signature" which could
complement the TN(M) classification.
PMID- 23153505
TI - Role of the investigator in phase 1 trials of anticancer drugs.
PMID- 23153506
TI - Tolerability, safety, pharmacokinetics, and efficacy of doxorubicin-loaded anti
EGFR immunoliposomes in advanced solid tumours: a phase 1 dose-escalation study.
AB - BACKGROUND: Results of preclinical studies have shown that EGFR immunoliposomes
have substantial antitumour effects. We aimed to assess the tolerability, safety,
pharmokinetics, and efficacy of anti-EGFR immunoliposomes loaded with doxorubicin
(anti-EGFR ILs-dox) in patients with solid tumours. METHODS: In this first-in
man, open-label, phase 1 clinical study, we enrolled patients at University
Hospital of Basel, Switzerland, who had EGFR-overexpressing advanced solid
tumours no longer amenable to standard treatment. Anti-EGFR ILs-dox nanoparticles
were constructed by covalently linking pegylated liposomes containing doxorubicin
to antigen-binding fragments (Fab') of cetuximab. We intravenously infused the
nanoparticle at escalating doses (doxorubicin 5 mg/m(2), 10 mg/m(2), 20 mg/m(2),
30 mg/m(2), 40 mg/m(2), 50 mg/m(2), and 60 mg/m(2)) once every 4 weeks for a
maximum of six cycles. The primary endpoint was to establish the maximum
tolerated dose. We analysed patients who received at least one dose of study
drug. This study is registered with ClinicalTrials.gov, number NCT01702129.
FINDINGS: Between Jan 30, 2007, and March 4, 2010, we gave the drug to 29
patients, three of whom were withdrawn from the study because we could not
complete a safety assessment. Of the 26 patients assessed for the primary
endpoint, two who received a dose of 60 mg/m(2) had dose-limiting toxicities (one
had neutropenia and the other had anaemia); therefore, the maximum tolerated dose
was defined as 50 mg/m(2). At all lower doses, anti-EGFR ILs-dox was well
tolerated; grade 1 skin toxicity occurred in two patients only. We recorded 22
serious adverse events (SAEs) in 17 patients, mostly due to tumour progression.
Three SAEs were fatal. Only three SAEs (febrile neutropenia, septicaemia, and a
fatal massive oral bleed) were probably or possibly related to study drug. No
patients had palmar-plantar erythrodysaesthesia, alopecia, cardiotoxicity, or
cumulative toxicity. Best response to treatment included one complete response,
one partial response, and ten stable disease lasting 2-12 months (median 5.75
months). INTERPRETATION: Because anti-EGFR ILs-dox was well tolerated up to 50 mg
doxorubicin per m(2), and we recorded clinical activity, further assessment of
this nanoparticle at this dose in phase 2 trials is warranted. FUNDING: Cancer
League Basel, Swiss Cancer League, Schoenmakers-Muller Foundation, and Werner
Geissberger Foundation.
PMID- 23153507
TI - A missense mutation in the ITGA8 gene, a cell adhesion molecule gene, is
associated with schizophrenia in Japanese female patients.
AB - BACKGROUND: Cell adhesion molecules (CAMs) play pivotal role in the development
of the central nervous system (CNS) and have also been reported to play role in
the pathophysiology of schizophrenia. Missense mutations in the CAMs genes might
alter the binding of their ligands, increasing the vulnerability to develop
schizophrenia. METHODS: We selected 15 missense mutations in the CAMs genes of
the CNS reported in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and
examined the association between these mutations and schizophrenia in 278
patients and 284 control subjects (first batch). We also genotyped the positive
single nucleotide polymorphisms (SNPs) in 567 patients and 710 control subjects
(second batch) and in 635 patients and 639 control subjects (replication
samples). RESULTS: Genotypic and allelic distributions of rs2298033 in the ITGA8
gene between the schizophrenia and control groups were significantly different in
the first batch (p=0.005 and 0.007, respectively). Gender-based analysis revealed
that the allelic and genotypic distributions of rs2298033 in the ITGA8 were
significantly different between the schizophrenia and control groups among
females in both batches (p=0.010, 0.011 and 0.0086, 0.010, respectively) but not
among males. Combine analysis of rs2298033 with the replication samples revealed
a more significant differences (p=0.0032; 0.0035 in the overall subjects and
p=0.0024; 0.0025 in the female subjects, respectively). The significant
differences for rs2802808 of the NFASC gene were only observed in the female
subgroup of the first batch. CONCLUSION: These results suggest that the ITGA8
gene might have gender-specific roles in the development of schizophrenia.
Further replication and functional studies are required to confirm these
findings.
PMID- 23153508
TI - Rac1/PAK1 signaling promotes epithelial-mesenchymal transition of podocytes in
vitro via triggering beta-catenin transcriptional activity under high glucose
conditions.
AB - Ras-related C3 botulinum toxin substrate 1 (Rac1), together with its major
downstream effector p21-activated kinase 1 (PAK1), has been identified a central
role in cellular events such as cell cytoskeletal remodeling that contributed to
cell migration and epithelial-mesenchymal transition (EMT). And there are data
implicating that podocytes underwent EMT under pathological conditions. However,
little is known about mechanisms of podocytes undergoing EMT. To address this, we
assessed the cellular changes of podocytes after high glucose stimulation in
vitro, detected the effects of Rac1/PAK1 signaling on podocytes in response to
the stimuli, and investigated interactions of Rac1/PAK1 axis with beta-catenin
and Snail under high glucose conditions. We found that in vitro high glucose
treatment led to remarkable down-regulation of nephrin and P-cadherin, as well as
significant up-regulation of alpha-SMA and FSP-1, suggesting that in the presence
of high glucose, podocytes underwent EMT, during which Rac1/PAK1 signaling was
activated. And these were notably ameliorated by Rac1 gene knockdown.
Furthermore, beta-catenin and Snail nuclear translocation were triggered by
Rac1/PAK1 axis, which were both markedly reversed via Rac1 gene knockdown or
pretreatment of IPA-3, a PAK1 inhibitor. These findings elaborated that Rac1/PAK1
signaling contributed to high glucose-induced podocyte EMT via promoting beta
catenin and Snail transcriptional activities, which could be a potential
mechanism involved in podocytes injury in response to stimuli under diabetic
conditions.
PMID- 23153509
TI - Down-regulation of NAMPT expression by miR-182 is involved in Tat-induced HIV-1
long terminal repeat (LTR) transactivation.
AB - Tat's transactivating activity is controlled by sirtuin 1 (SIRT1) that connects
HIV transcription with the metabolic state of the cell. Nicotinamide
phosphoribosyltransferase (NAMPT) is a key enzyme in the salvaging pathway for
the synthesis of nicotinamide adenine dinucleotide (NAD(+)) that is involved in
energy metabolism. Host encoded microRNAs (miRNAs) may influence viral
replication. In this study, our goal was aimed to investigate the regulation of
miR-182 in TZM-bl cells and explore the mechanisms by which miR-182 influenced
Tat-induced HIV-1 transactivation through targeting at down-regulation of NAMPT
expression. We showed that miR-182 was up-regulated when Tat was expressed in TZM
bl cells. MiR-182 significantly inhibited NAMPT protein expression by acting on
the 3'-UTR of the NAMPT mRNA. MiR-182 was involved in Tat-induced NAD(+)
depletion, down-regulation of SIRT1 protein expression and activity, increased
acetylation of p65. Forced expression of "miR-182 mimics" increased Tat-induced
LTR transactivation. Our results uncover previously unknown links between Tat and
a specific host cell miRNA that targets NAMPT. Our results suggest that
strategies to augment NAMPT protein expression by down-regulation of miR-182 may
have therapeutic benefits to prevent HIV-1 replication.
PMID- 23153511
TI - Evolution of improvement and cumulative culture.
AB - Humans have created highly developed cultures, brought about by iterative
improvements in technology. Using a mathematical model, I investigated the
conditions under which cultural traits tend to be improved for a higher level of
culture to evolve. In the model, I consider three ways of learning: individual
learning, simple social learning, and improvements of socially learned cultural
traits (social improvement). I obtain the evolutionarily stable number of
cultural traits acquired through each way of learning. I show that organisms
improve many socially learned cultural traits under the following conditions: (1)
environmental stability is intermediate; (2) the environment is severe; (3) the
success rate of individual learning is high; (4) the utility of cultural traits
acquired by individual learning is large; (5) the accuracy of social learning is
high; and (6) the increase in the utility of beneficial cultural traits attained
by social improvement is large. I also show that when organisms have greater
ability for social improvement, the average utility of the beneficial cultural
trait increases, the proportion of beneficial cultural traits among all cultural
traits decreases, and the total number of cultural traits acquired by the three
ways of learning is constant. These results shed light on the origins of human
cumulative culture.
PMID- 23153510
TI - Deletion of microRNA miR-223 increases Langerhans cell cross-presentation.
AB - Langerhans cells (LCs) are skin-residential dendritic cells that regulate skin
immunity. MicroRNAs (miRNAs) are key regulators in the control of biological
functions in a variety of cell types. Deletion of all miRNAs interrupts the
homeostasis and function of epidermal LCs. However, the roles of individual
miRNAs in regulating LC development and function are still completely unknown.
MiRNA miR-223 is especially expressed in the myeloid compartment. Here, we
reported that miR-223 is highly expressed in freshly isolated epidermal LCs, and
tested whether miR-223 regulates LC development and function using miR-223
knockout (KO) mice. We found that the number, maturation, migration and
phagocytic capacity of LCs were comparable between miR-223KO and wild-type mice.
However, lack of miR-223 significantly increases LCs-mediated antigen-specific
CD8(+) T cell proliferation in vivo and in vitro, while LCs from KO and WT mice
showed comparable stimulation for antigen-specific CD4(+) T cells. Our data
suggest that miR-223 negatively regulates LC cross-presentation, but may not be
required for normal LC homeostasis and development.
PMID- 23153512
TI - Proposed model for in vitro interaction between fenitrothion and DNA, by using
competitive fluorescence, (31)P NMR, (1)H NMR, FT-IR, CD and molecular modeling.
AB - In this work we proposed a model for in vitro interaction of fenitrothion (FEN)
with calf thymus-DNA by combination of multispectroscopic and two dimensional
molecular modeling (ONIOM) methods. The circular dichroism results showed that
FEN changes the conformation of B-DNA and caused some changes to C-DNA form. The
FT-IR results confirmed a partial intercalation between FEN and edges of all base
pairs. The competitive fluorescence, using methylene blue as fluorescence probe,
in the presence of increasing amounts of FEN, revealed that FEN is able to
release the non-intercalated methylene blue from the DNA. The weak chemical shift
and peak broadening of (1)H NMR spectrum of FEN in the presence of DNA confirmed
a non-intercalation mode. The (31)P NMR showed that FEN interacts more with DNA
via its -NO2 moiety. The ONIOM, based on the hybridization of QM/MM (DFT, 6.31++G
(d,p)/UFF) methodology, was also performed by Gaussian 2003 package. The results
revealed that the interaction is base sequence dependent, and FEN interacts more
with AT base sequences.
PMID- 23153513
TI - Circumcision benefits outweigh risks, but parents should choose according to
revised AAP policy.
PMID- 23153514
TI - Effects of natural radiation, photosynthetically active radiation and artificial
ultraviolet radiation-B on the chloroplast organization and metabolism of
Porphyra acanthophora var. brasiliensis (Rhodophyta, Bangiales).
AB - We undertook a study of Porphyra acanthophora var. brasiliensis to determine its
responses under ambient conditions, photosynthetically active radiation (PAR),
and PAR+UVBR (ultraviolet radiation-B) treatment, focusing on changes in
ultrastructure, and cytochemistry. Accordingly, control ambient samples were
collected in the field, and two different treatments were performed in the
laboratory. Plants were exposed to PAR at 60 MUmol photons m-2 s-1 and PAR + UVBR
at 0.35 W m-2 for 3 h per day during 21 days of in vitro cultivation. Confocal
laser scanning microscopy analysis of the vegetative cells showed single stellate
chloroplast in ambient and PAR samples, but in PAR+UVBR-exposed plants, the
chloroplast showed alterations in the number and form of arms. Under PAR+UVBR
treatment, the thylakoids of the chloroplasts were disrupted, and an increase in
the number of plastoglobuli was observed, in addition to mitochondria, which
appeared with irregular, disrupted morphology compared to ambient and PAR
samples. After UVBR exposure, the formation of carpospores was also observed.
Plants under ambient conditions, as well as those treated with PAR and PAR+UVBR,
all showed different concentrations of enzymatic response, including glutathione
peroxidase and reductase activity. In summary, the present study demonstrates
that P. acanthophora var. brasiliensis shows the activation of distinct
mechanisms against natural radiation, PAR and PAR+UVBR.
PMID- 23153515
TI - The impact of a multifaceted ergonomic intervention program on promoting
occupational health in community nurses.
AB - INTRODUCTION: Community nurses are exposed to high physical demands at work
resulting in musculoskeletal disorders. The present study examined the short- and
long-term benefits of a multifaceted intervention program designed especially for
community nurses in Hong Kong. METHODS: Fifty community nurses working in 4 local
hospitals participated in the study. All of them underwent an 8-week intervention
program consisting of ergonomic training, daily exercise program, equipment
modification, computer workstation assessment and typing training. RESULTS: All
participants showed significant improvement in musculoskeletal symptoms and
functional outcomes comparing pre- and post-intervention results. Significant
reduction in symptom score was observed at 1-year follow-up compared to post
intervention. Symptomatic group (n=40) showed more significant changes overall
compared to asymptomatic group (n=10). CONCLUSION: Results support the positive
benefits, both short- and long-term, of the multifaceted ergonomic intervention
programme for community nurses.
PMID- 23153516
TI - Identification and characterization of novel microRNA candidates from deep
sequencing.
AB - In our previous study, we screened a candidate new microRNA (miRNA) based on the
deep sequencing and bioinformatics analysis. In this paper, we evaluated the
novel miRNA in the following experiment: 1) the secondary structure of the
precursor of novel-miR has the characteristic of a stem-loop hairpin structure,
and mature miRNA is far from loops and bulges. 2) we used BLAST (Basic Local
Alignment Search Tool) to compare the novel-miR sequence to that found in the
GenBank. Novel-miR sequence existed in Mus musculus, Drosophila grimshawi, Rattus
norvegicus, Xenopus laevis, Spodoptera frugiperda, Papio anubis, Salmo salar and
so on. Then multiple sequence alignment (MSA) showed that sequence from 5 to 11
bp and 13 to 17 bp exhibited 100% similarity, where there is significant sequence
conservation. Novel-miR showed similarity in the seed region with the known miR
3675-3p, indicating that these miRNAs are likely to belong to the same family and
thus may share common biology. 3) novel-miR from MCF-7 and MB-MDA-231 was
validated by Northern blot and detected in the serum and tissue samples of BC
patients, respectively, by real-time PCR. The data showed that novel-miR was
downregulated in the BC cancerous tissues and serum of breast cancer patients
(P<0.05). 4) transfection of novel-miR mimics into MCF-7 cell significantly
inhibited cell growth detected by CCK-8 assay (P<0.05). 5) to identify the mRNA
targets of novel-miR, we performed a computational screen for genes with novel
miR complementary sites in their 3'-UTR using several open access databases. In
addition, we used the CapitalBio(r) Molecule Annotation System V3.0 to perform
gene ontology (GO) analysis on the target genes of novel-miR and specific
biological process categories were enriched. 7 genes (CUL3, KRAS, ETS1, MNT,
CNTN3, CCNK and FOXO3) which have a high prediction score and are associated with
cell proliferation, apoptosis and cell cycle were chosen. 3'-UTR luciferase
report assay suggested that miR-BS1 negatively regulated CNTN3. In the
conclusion, novel-miR, named miR-3675b, is a true, functional and novel miRNA.
Candidate novel miRNA from deep sequencing which will be qualified as a "real"
miRNA must be validated by a series of functional experiments.
PMID- 23153517
TI - Medicinal property, phytochemistry and pharmacology of several Jatropha species
(Euphorbiaceae): a review.
AB - The genus Jatropha (Euphorbiaceae) comprises of about 170 species of woody trees,
shrubs, subshrubs or herbs in the seasonally dry tropics of the Old and the New
World. They are used in medicinal folklore to cure various diseases of 80% of the
human population in Africa, Asia and Latin America. Species from this genus have
been popular to cure stomachache, toothache, swelling, inflammation, leprosy,
dysentery, dyscrasia, vertigo, anemia, diabetis, as well as to treat HIV and
tumor, opthalmia, ringworm, ulcers, malaria, skin diseases, bronchitis, asthma
and as an aphrodisiac. They are also employed as ornamental plants and energy
crops. Cyclic peptides alkaloids, diterpenes and miscellaneous compounds have
been reported from this genus. Extracts and pure compounds of plants from this
genus are reported for cytotoxicity, tumor-promoting, antimicrobial,
antiprotozoal, anticoagulant, immunomodulating, anti-inflammatory, antioxidant,
protoscolicidal, insecticidal, molluscicidal, inhibition AChE and toxicity
activities.
PMID- 23153518
TI - Tetracyclic triterpenoids and terpenylated coumarins from the bark of Ailanthus
altissima ("Tree of Heaven").
AB - Tetracyclic triterpenoids (named as altissimanins A-E, 1-5) and a terpenylated
coumarin (denominated as altissimacoumarin G, 6), along with fifteen known
compounds (7-21) were isolated from the bark of Ailanthus altissima. Structures
of compounds 1-6 were established by spectroscopic methods and chemical
transformations. Altissimanin A (1) is a tirucallane-type triterpenoid bearing an
uncommon oxetane ring in the side-chain, while altissimanins D (4) and E (5) are
two unprecedented dimers each consisting of one tirucallane-type and one
dammarane-type triterpenoid moiety. All the isolates were evaluated for their
cytotoxic effects against a small panel of human cancer cell lines.
PMID- 23153519
TI - Immediate breast reconstruction using porcine acellular dermal matrix
(StratticeTM): long-term outcomes and complications.
AB - BACKGROUND: There has been limited reported experience with the use of
StratticeTM (LifeCell Corp., Branchburg, NJ), a porcine-derived acellular dermal
matrix, in implant-based breast reconstruction. The purpose of this study is to
evaluate our experience with this matrix. METHODS: Patients who underwent
immediate single-stage or two-stage implant-based breast reconstruction with the
assistance of Strattice were included in this study. Patient charts were reviewed
for indications for mastectomy, adjunctive radiotherapy use, implant or expander
volume, length of follow-up period, and type and incidence of complications
during the follow-up period. Biopsies of Strattice were taken for histological
analyses. RESULTS: A total of 105 reconstructions were performed in 54 patients:
77% were prophylactic and 23% were oncologic. All, but 4, reconstructions were
single stage. Mean implant volume of single-stage reconstructions were 444.1
(range: 150-700 cc) and mean expander volume after completion of expansion was
400 (range: 350-450). Mean follow-up period was 41.3 months (range: 35.5-48.4
months). Total complication rate was 8.6%. Complications occurred in 9 breasts:
implant loss or explantation (3.8%), infection (3.8%), skin breakdown or necrosis
(2.9%), seroma (1.9%), implant exposure (1.0%), and delayed skin healing (1.0%).
Histological analyses of implanted Strattice revealed a viable matrix with
fibroblast infiltration and revascularization. CONCLUSIONS: Over a mean 3.5-year
follow-up period, low complication rates and good outcomes were observed with the
use of Strattice that are comparable to those reported with human acellular
dermal matrices.
PMID- 23153520
TI - Correcting radial shift in fractures of the distal radius.
PMID- 23153521
TI - What is the nature of serotonergic abnormalities in human aggression?
PMID- 23153522
TI - Adhesion of Fusobacterium necrophorum to bovine endothelial cells is mediated by
outer membrane proteins.
AB - Fusobacterium necrophorum, a Gram-negative anaerobe, is frequently associated
with suppurative and necrotic infections of animals and humans. The organism is a
major bovine pathogen, and in cattle, the common fusobacterial infections are
hepatic abscesses, foot rot, and necrotic laryngitis. The species comprises two
subspecies: F. necrophorum subsp. necrophorum and F. necrophorum subsp.
funduliforme. Bacterial adhesion to the host cell surface is a critical initial
step in the pathogenesis, and outer membrane proteins (OMP) play an important
role in adhesion and establishment of certain Gram-negative bacterial infections.
The means by which F. necrophorum attaches to epithelial or endothelial cells has
not been determined. We evaluated whether OMP of F. necrophorum, isolated from a
liver abscess, mediated adhesion to bovine endothelial cells (adrenal gland
capillary endothelial cell line). The extent of binding of subsp. necrophorum to
the endothelial cells was higher than that of F. necrophorum subsp. funduliforme.
Trypsin treatment of bacterial cells decreased their binding to endothelial cells
indicating the protein nature of adhesins. Preincubation of endothelial cells
with OMP extracted from F. necrophorum decreased the binding of bacterial cells.
In addition, binding of each subspecies to endothelial cells was inhibited by
polyclonal antibodies raised against respective OMP and the antibody-mediated
inhibition was subspecies specific. The western blot analysis of OMP bound to
endothelial cells with anti-OMP antibodies showed four OMP of 17, 24, 40 and 74
kDa. We conclude that OMP of F. necrophorum play a role in adhesion of bacterial
cells to the endothelial cells.
PMID- 23153523
TI - [Medical specialty choice: what impact of teaching? Results of a survey of two
medical schools].
AB - BACKGROUND: Determinants of career choice are numerous. The impact of teaching
has not yet been reported. OBJECTIVES: The objectives were to assess determinants
of career choice among DCEM 4 (sixth year) medical students at Paris Descartes
University and Pierre-et-Marie-Curie University; and to determine the impact of
teaching on career choice. MATERIALS AND METHODS: Prospective study based on an
online survey, after the 2011 National Grading Examination, among 865 DCEM 4
students. Collection of socio-demographic data, commonly reported determinants of
medical specialty choice, and the impact of the teaching on this choice. RESULTS:
Two hundred and seven (24%) students (67% female) answered the survey. During
their medical studies, students changed their mind on their career choice an
average of 3 times (range 0-10). Nearly 60% of them made their final choice
during the fifth year. Choices varied significantly between the beginning and end
of the studies (P<0.0001), with interest in surgical and pediatric careers
falling significantly (P<0.0001 and p=0.0003 respectively). At the time of
expressing the final choice, surgical careers were mainly chosen by male students
(19.8% of males vs. 9.9% of females, P=0.04), whereas medical careers were chosen
equally by males and females (37.7% vs. 35.5%, P=0.75). The main determinant was
interest in the specialty (96% of students), followed by perceived quality of
life (56% of students). Teaching was a determinant for 74% of students, of whom
88% were influenced by the teaching they received during their clinical training.
In 42% of cases, the teacher did not belong to the university corpus. In 10% of
cases, students were discouraged from their choice by a teacher (a university
professor in 50%). DISCUSSION AND CONCLUSION: Our results highlight the impact of
both teaching and the teacher on medical students' career choice. If career
choice is now compelled in France by the "careers law", teaching is more than
ever an effective way of interesting students in specialties which might appear
less attractive. At a time when the selection of candidates for hospital
university careers is mainly based on publications, this study calls for
reflection on the evaluation of these candidates' teaching qualities.
PMID- 23153524
TI - Alisertib (MLN8237) an investigational agent suppresses Aurora A and B activity,
inhibits proliferation, promotes endo-reduplication and induces apoptosis in T
NHL cell lines supporting its importance in PTCL treatment.
AB - Peripheral T-cell lymphomas (PTCL) are a diverse group of rare non-Hodgkin
lymphomas (NHL) that carry a poor prognosis and are in need of effective
therapies. Alisertib (MLN8237) an investigational agent that inhibits Aurora A
Ser/Thr kinase has shown activity in PTCL patients. Here we demonstrate that
aurora A and B are highly expressed in T-cell lymphoma cell lines. In PTCL
patient samples aurora A was positive in 3 of 24 samples and co-expressed with
aurora B. Aurora B was positive in tumor cells in 22 of 32 samples. Of the
subtypes of PTCL, aurora B was over-expressed in PTCL (NOS) [73%], T-NHL [100%],
ALCL (Alk-Neg) [100%] and AITL [100%]. Treatment with MLN8237 inhibited PTCL cell
proliferation in CRL-2396 and TIB-48 cells with an IC50 of 80-100nM. MLN8237
induced endo-reduplication in a dose and time dependent manner in PTCL cell lines
leading to apoptosis demonstrated by flow cytometry and PARP-cleavage at
concentrations achieved in early phase clinical trials. Moreover, inhibition of
HisH3 and aurora A phosphorylation was dose dependent and strongly correlated
with endo-reduplication. The data provide a sound rationale for aurora inhibition
in PTCL as a therapeutic modality and warrants clinical trial evaluation.
PMID- 23153525
TI - Localization of the NRAS:BCL-2 complex determines anti-apoptotic features
associated with progressive disease in myelodysplastic syndromes.
AB - We have previously demonstrated that two prognostic features of myelodysplastic
syndromes (MDS) and acute myelogenous leukemia (AML), mutant NRAS and over
expressing BCL-2, cooperate physically and functionally in vivo. Screening of MDS
patient bone marrow (BM) identified NRAS:BCL-2 co-localization in 64% cases,
correlating with percentage BM blasts, apoptotic features and disease status
(p<0.0001). Localization of the complex at the plasma membrane or the
mitochondria correlated with disease and apoptosis features in MDS patients,
whilst caspase-9 mediated mechanism was elucidated in vivo and in vitro. The
intensity and localization of the RAS:BCL-2 complex merits further evaluation as
a novel biomarker of MDS.
PMID- 23153526
TI - Bone marrow dendritic cells are reduced in patients with high-risk
myelodysplastic syndromes.
AB - Dendritic cells (DC) are antigen-presenting cells that play a pivotal role in
coordinating functions of the immune system. Previous studies suggest that bone
marrow (BM) failure in myelodysplastic syndromes (MDS) may be in part immune
mediated, and that the high propensity for relapse may reflect decreased immune
surveillance. This study aimed to assess the frequency of DC in BM samples from
well-annotated untreated MDS patients by using 4-colour flow cytometry. DC levels
were markedly reduced in all subtypes of MDS. The clinical impact of this finding
on therapy response and relapse after, e.g. allogeneic stem cell transplantation
warrants further investigation.
PMID- 23153528
TI - Metastatic ability: adapting to a tissue site unseen.
AB - The microenvironment of the primary as well as the metastatic tumor sites can
determine the ability for a disseminated tumor to progress. In this issue of
Cancer Cell, Calon and colleagues find that systemic TGF-beta can facilitate
colon cancer metastatic engraftment and expansion.
PMID- 23153527
TI - Association of retinol binding protein 4 with risk of gestational diabetes.
AB - AIM: We investigated association of maternal retinol binding protein 4 (RBP4)
with risk of gestational diabetes (GDM). METHODS: GDM cases (N=173) and controls
(N=187) were selected from among participants of a cohort study of risk factors
of pregnancy complications. Early pregnancy (16 weeks on average) serum RBP4
concentration was measured using an ELISA-based immunoassay. Logistic regression
was used to estimate unadjusted and adjusted odds ratios (ORs/aORs) and 95%
confidence intervals (95%CI). RESULTS: Mean serum RBP4 was significantly higher
among GDM cases compared with controls (47.1 vs. 41.1 MUg/ml, respectively; p
value <0.05). Participants in the highest quartile for serum RBP4 had a 1.89-fold
higher risk of GDM compared with participants in the lowest quartile (95%CI: 1.05
3.43). However, this relationship did not reach statistical significance after
adjustment for confounders (aOR: 1.54; 95%CI: 0.82-2.90). Women who were >=35
years old and who had high RBP4 (>=38.3 MUg/ml, the median) had a 2.31-fold
higher risk of GDM compared with women who were <35 years old and had low RBP4
(<38.3 MUg/ml) (aOR: 2.31; 95%CI: 1.26-4.23; p-value for interaction=0.021).
CONCLUSION: Overall, there is modest evidence of a positive association of early
pregnancy elevated RBP4 concentration with increased GDM risk, particularly among
women with advanced age.
PMID- 23153529
TI - PGAMgnam style: a glycolytic switch controls biosynthesis.
AB - Therapeutic strategies that target glycolysis and biosynthetic pathways in cancer
cells are currently the main focus of research in the field of cancer metabolism.
In this issue of Cancer Cell, Hitosugi and colleagues show that targeting PGAM1
could be a way of "killing two birds with one stone".
PMID- 23153530
TI - BMP meets AML: induction of BMP signaling by a novel fusion gene promotes
pediatric acute leukemia.
AB - In this issue of Cancer Cell, Gruber et al. report that a significant proportion
of children with acute megakaryoblastic leukemia acquire a translocation that
confers enhanced BMP signaling and promotes self-renewal of hematopoietic
progenitors. This study presents novel therapeutic targets that may lead to
improved therapies for this aggressive leukemia.
PMID- 23153531
TI - Epigenetic therapy leaps ahead with specific targeting of EZH2.
AB - The Polycomb epigenetic silencing protein EZH2 is affected by gain-of-function
somatic mutations in B cell lymphomas. Two recent reports describe the
development of highly selective EZH2 inhibitors and reveal mutant EZH2 as playing
an essential role in maintaining lymphoma proliferation. EZH2 inhibitors are thus
a promising new targeted therapy for lymphoma.
PMID- 23153532
TI - Dependency of colorectal cancer on a TGF-beta-driven program in stromal cells for
metastasis initiation.
AB - A large proportion of colorectal cancers (CRCs) display mutational inactivation
of the TGF-beta pathway, yet, paradoxically, they are characterized by elevated
TGF-beta production. Here, we unveil a prometastatic program induced by TGF-beta
in the microenvironment that associates with a high risk of CRC relapse upon
treatment. The activity of TGF-beta on stromal cells increases the efficiency of
organ colonization by CRC cells, whereas mice treated with a pharmacological
inhibitor of TGFBR1 are resilient to metastasis formation. Secretion of IL11 by
TGF-beta-stimulated cancer-associated fibroblasts (CAFs) triggers GP130/STAT3
signaling in tumor cells. This crosstalk confers a survival advantage to
metastatic cells. The dependency on the TGF-beta stromal program for metastasis
initiation could be exploited to improve the diagnosis and treatment of CRC.
PMID- 23153533
TI - Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote
tumor growth.
AB - It is unclear how cancer cells coordinate glycolysis and biosynthesis to support
rapidly growing tumors. We found that the glycolytic enzyme phosphoglycerate
mutase 1 (PGAM1), commonly upregulated in human cancers due to loss of TP53,
contributes to biosynthesis regulation in part by controlling intracellular
levels of its substrate, 3-phosphoglycerate (3-PG), and product, 2
phosphoglycerate (2-PG). 3-PG binds to and inhibits 6-phosphogluconate
dehydrogenase in the oxidative pentose phosphate pathway (PPP), while 2-PG
activates 3-phosphoglycerate dehydrogenase to provide feedback control of 3-PG
levels. Inhibition of PGAM1 by shRNA or a small molecule inhibitor PGMI-004A
results in increased 3-PG and decreased 2-PG levels in cancer cells, leading to
significantly decreased glycolysis, PPP flux and biosynthesis, as well as
attenuated cell proliferation and tumor growth.
PMID- 23153534
TI - Loss of the Par3 polarity protein promotes breast tumorigenesis and metastasis.
AB - Loss of epithelial organization is a hallmark of carcinomas, but whether polarity
regulates tumor growth and metastasis is poorly understood. To address this
issue, we depleted the Par3 polarity gene by RNAi in combination with oncogenic
Notch or Ras(61L) expression in the murine mammary gland. Par3 silencing
dramatically reduced tumor latency in both models and produced invasive and
metastatic tumors that retained epithelial marker expression. Par3 depletion was
associated with induction of MMP9, destruction of the extracellular matrix, and
invasion, all mediated by atypical PKC-dependant JAK/Stat3 activation.
Importantly, Par3 expression is significantly reduced in human breast cancers,
which correlates with active aPKC and Stat3. These data identify Par3 as a
regulator of signaling pathways relevant to invasive breast cancer.
PMID- 23153535
TI - Differential remodeling of actin cytoskeleton architecture by profilin isoforms
leads to distinct effects on cell migration and invasion.
AB - Dynamic actin cytoskeletal reorganization is integral to cell motility. Profilins
are well-characterized regulators of actin polymerization; however, functional
differences among coexpressed profilin isoforms are not well defined. Here, we
demonstrate that profilin-1 and profilin-2 differentially regulate membrane
protrusion, motility, and invasion; these processes are promoted by profilin-1
and suppressed by profilin-2. Compared to profilin-1, profilin-2 preferentially
drives actin polymerization by the Ena/VASP protein, EVL. Profilin-2 and EVL
suppress protrusive activity and cell motility by an actomyosin contractility
dependent mechanism. Importantly, EVL or profilin-2 downregulation enhances
invasion in vitro and in vivo. In human breast cancer, lower EVL expression
correlates with high invasiveness and poor patient outcome. We propose that
profilin-2/EVL-mediated actin polymerization enhances actin bundling and
suppresses breast cancer cell invasion.
PMID- 23153536
TI - ATF4 regulates MYC-mediated neuroblastoma cell death upon glutamine deprivation.
AB - Oncogenic Myc alters mitochondrial metabolism, making it dependent on exogenous
glutamine (Gln) for cell survival. Accordingly, Gln deprivation selectively
induces apoptosis in MYC-overexpressing cells via unknown mechanisms. Using MYCN
amplified neuroblastoma as a model, we identify PUMA, NOXA, and TRB3 as executors
of Gln-starved cells. Gln depletion in MYC-transformed cells induces apoptosis
through ATF4-dependent, but p53-independent, PUMA and NOXA induction. MYC
transformed cells depend on both glutamate-oxaloacetate transaminase and
glutamate dehydrogenase to maintain Gln homeostasis and suppress apoptosis.
Consequently, either ATF4 agonists or glutaminolysis inhibitors potently induce
apoptosis in vitro and inhibit tumor growth in vivo. These results reveal
mechanisms whereby Myc sensitizes cells to apoptosis, and validate ATF4 agonists
and inhibitors of Gln metabolism as potential Myc-selective cancer therapeutics.
PMID- 23153537
TI - Aberrant overexpression of IL-15 initiates large granular lymphocyte leukemia
through chromosomal instability and DNA hypermethylation.
AB - How inflammation causes cancer is unclear. Interleukin-15 (IL-15) is a pro
inflammatory cytokine elevated in human large granular lymphocyte (LGL) leukemia.
Mice overexpressing IL-15 develop LGL leukemia. Here, we show that prolonged in
vitro exposure of wild-type (WT) LGL to IL-15 results in Myc-mediated
upregulation of aurora kinases, centrosome aberrancies, and aneuploidy.
Simultaneously, IL-15 represses miR-29b via induction of Myc/NF-kappaBp65/Hdac-1,
resulting in Dnmt3b overexpression and DNA hypermethylation. All this is
validated in human LGL leukemia. Adoptive transfer of WT LGL cultured with IL-15
led to malignant transformation in vivo. Drug targeting that reverses miR-29b
repression cures otherwise fatal LGL leukemia. We show how excessive IL-15
initiates cancer and demonstrate effective drug targeting for potential therapy
of human LGL leukemia.
PMID- 23153538
TI - Crosstalk between ROR1 and the Pre-B cell receptor promotes survival of t(1;19)
acute lymphoblastic leukemia.
AB - We report that t(1;19) ALL cells universally exhibit expression of and dependence
on the cell surface receptor ROR1. We further identify t(1;19) ALL cell
sensitivity to the kinase inhibitor dasatinib due to its inhibition of the pre-B
cell receptor (pre-BCR) signaling complex. These phenotypes are a consequence of
developmental arrest at an intermediate/late stage of B-lineage maturation.
Additionally, inhibition of pre-BCR signaling induces further ROR1 upregulation,
and we identify distinct ROR1 and pre-BCR downstream signaling pathways that are
modulated in a counterbalancing manner-both leading to AKT phosphorylation.
Consistent with this, AKT phosphorylation is transiently eliminated after
dasatinib treatment, but is partially restored following dasatinib potentiation
of ROR1 expression. Consequently, ROR1 silencing accentuates dasatinib killing of
t(1;19) ALL cells.
PMID- 23153541
TI - SnapShot: Acute myeloid leukemia.
PMID- 23153539
TI - Relief of profound feedback inhibition of mitogenic signaling by RAF inhibitors
attenuates their activity in BRAFV600E melanomas.
AB - BRAF(V600E) drives tumors by dysregulating ERK signaling. In these tumors, we
show that high levels of ERK-dependent negative feedback potently suppress ligand
dependent mitogenic signaling and Ras function. BRAF(V600E) activation is Ras
independent and it signals as a RAF-inhibitor-sensitive monomer. RAF inhibitors
potently inhibit RAF monomers and ERK signaling, causing relief of ERK-dependent
feedback, reactivation of ligand-dependent signal transduction, increased Ras
GTP, and generation of RAF-inhibitor-resistant RAF dimers. This results in a
rebound in ERK activity and culminates in a new steady state, wherein ERK
signaling is elevated compared to its initial nadir after RAF inhibition. In this
state, ERK signaling is RAF inhibitor resistant, and MEK inhibitor sensitive, and
combined inhibition results in enhancement of ERK pathway inhibition and
antitumor activity.
PMID- 23153542
TI - Intrauterine stress and male cohort quality: the case of September 11, 2001.
AB - Empirical research and the theory of natural selection assert that male mortality
more than female mortality responds to ambient stressors in utero. Although
population stressors may adversely damage males that survive to birth, the rival
culled cohort hypothesis contends that males born during stressful times may
exhibit better health than males in other cohorts because fetal loss has "culled"
the frailest males. We tested these hypotheses by examining child developmental
outcomes in a U.S. birth cohort reportedly affected in utero by the September 11,
2001 attacks. We used as outcomes the Bayley cognitive score and child height-for
age from the Early Childhood Longitudinal Study-Birth Cohort. Previous research
demonstrates a male-specific effect of 9/11 on California infants born in
December 2001. We, therefore, compared cognition and height of this cohort with
males born prior to the 9/11 attacks. We controlled for unobserved confounding
across gender, season, and region by using triple-difference regression models (N
= 6950). At 24 months, California males born in December scored greater than
expected in cognitive ability (coef = 9.55, standard error = 3.37; p = 0.004). We
observed no relation with height. Results remained robust to alternative
specifications. Findings offer partial support for the culled cohort hypothesis
in that we observed greater than expected cognitive scores at two years of age
among a cohort of males affected by 9/11 in utero. Contemporary population
stressors may induce male-specific culling, thereby resulting in relatively
improved development among males that survive to birth.
PMID- 23153543
TI - Including quality attributes in efficiency measures consistent with net benefit:
creating incentives for evidence based medicine in practice.
AB - Evidence based medicine supports net benefit maximising therapies and strategies
in processes of health technology assessment (HTA) for reimbursement and subsidy
decisions internationally. However, translation of evidence based medicine to
practice is impeded by efficiency measures such as cost per case-mix adjusted
separation in hospitals, which ignore health effects of care. In this paper we
identify a correspondence method that allows quality variables under control of
providers to be incorporated in efficiency measures consistent with maximising
net benefit. Including effects framed from a disutility bearing (utility
reducing) perspective (e.g. mortality, morbidity or reduction in life years) as
inputs and minimising quality inclusive costs on the cost-disutility plane is
shown to enable efficiency measures consistent with maximising net benefit under
a one to one correspondence. The method combines advantages of radial properties
with an appropriate objective of maximising net benefit to overcome problems of
inappropriate objectives implicit with alternative methods, whether specifying
quality variables with utility bearing output (e.g. survival, reduction in
morbidity or life years), hyperbolic or exogenous variables. This correspondence
approach is illustrated in undertaking efficiency comparison at a clinical
activity level for 45 Australian hospitals allowing for their costs and mortality
rates per admission. Explicit coverage and comparability conditions of the
underlying correspondence method are also shown to provide a robust framework for
preventing cost-shifting and cream-skimming incentives, with appropriate
qualification of analysis and support for data linkage and risk adjustment where
these conditions are not satisfied. Comparison on the cost-disutility plane has
previously been shown to have distinct advantages in comparing multiple
strategies in HTA, which this paper naturally extends to a robust method and
framework for comparing efficiency of health care providers in practice.
Consequently, the proposed approach provides a missing link between HTA and
practice, to allow active incentives for evidence based net benefit maximisation
in practice.
PMID- 23153540
TI - An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive
subtype of pediatric acute megakaryoblastic leukemia.
AB - To define the mutation spectrum in non-Down syndrome acute megakaryoblastic
leukemia (non-DS-AMKL), we performed transcriptome sequencing on diagnostic
blasts from 14 pediatric patients and validated our findings in a
recurrency/validation cohort consisting of 34 pediatric and 28 adult AMKL
samples. Our analysis identified a cryptic chromosome 16 inversion
(inv(16)(p13.3q24.3)) in 27% of pediatric cases, which encodes a CBFA2T3-GLIS2
fusion protein. Expression of CBFA2T3-GLIS2 in Drosophila and murine
hematopoietic cells induced bone morphogenic protein (BMP) signaling and resulted
in a marked increase in the self-renewal capacity of hematopoietic progenitors.
These data suggest that expression of CBFA2T3-GLIS2 directly contributes to
leukemogenesis.
PMID- 23153544
TI - The re-construction of women's sexual lives after pelvic radiotherapy: a critique
of social constructionist and biomedical perspectives on the study of female
sexuality after cancer treatment.
AB - Pelvic radiotherapy creates physical effects and psychological responses that
negatively affect the sexual health of women and couples, yet these sexual
consequences are not frequently researched or clinically assessed. This focused
ethnographic study explored factors that influence the clinical assessment of
treatment-induced female sexual difficulties after pelvic radiotherapy within
routine medical follow-up. Participant observation of follow-up clinics (n = 69)
and in-depth interviews with 24 women, 5 partners and 20 health professionals
were undertaken at two cancer centres in the South East of England from 2005 to
2006. Thematic analysis of interview transcripts resulted in five emergent
themes, two of which are explored in detail within this paper. A social
constructionist approach to human sexuality was used to explore representations
of female sexuality in oncology follow-up constructed by clinicians, women and
their partners. Yet neither social constructionist nor biomedical (the
predominant model in medical follow-up) perspectives on human sexuality provided
an adequate interpretation of these study findings. This paper argues that the
comprehensive study and practice of sexual rehabilitation in oncology requires a
synthesis of both biomedical and social constructionist perspectives in order to
capture the complex, subjective and embodied nature of the female sexual response
in both health and illness.
PMID- 23153545
TI - Sonodynamic and sonocatalytic damage of BSA molecules by Cresol Red, Cresol Red
DA and Cresol Red-DA-Fe under ultrasonic irradiation.
AB - The interaction of Cresol Red derivatives (Cresol Red (o-Cresolsulfonphthalein),
Cresol Red-DA (3,3'-Bis [N,N-di (carboxymethyl) aminomethyl]-o
cresolsulfonphthalein) and Cresol Red-DA-Fe(III) (3,3'-Bis [N,N-di
(carboxymethyl) aminomethyl]-o-cresolsulfonphthalein-Ferrous(III)) with bovine
serum albumin (BSA) were studied by the combination of ultraviolet spectroscopy,
circular dichroism (CD) spectroscopy, fluorescence spectroscopy and synchronous
fluorescence spectroscopy. On that basis, the sonodynamic and sonocatalytic
damages of Cresol Red derivatives to BSA under ultrasonic irradiation were also
investigated by means of corresponding spectrum technology. Meanwhile, some
influenced factors such as ultrasonic irradiation time, Cresol Red derivatives
concentration and ionic strength on the damage degree of BSA molecules were also
reviewed. In addition, the binding site and damage site of BSA molecules were
estimated by synchronous fluorescence spectra. Finally, the results of oxidation
extraction photometry (OEP) using several reactive oxygen species (ROS)
scavengers indicated that the damage of BSA molecules is mainly due to the
generation of ROS. Perhaps, this paper may offer some important subjects for
broadening the application of Cresol Red derivatives in sonodynamic therapy (SDT)
and sonocatalytic therapy (SCT) technologies for tumor treatment.
PMID- 23153546
TI - Changes in male hormone profile after occupational organophosphate exposure. A
longitudinal study.
AB - There is a growing concern about the endocrine effects of long-term, low-level
exposure to organophosphate (OP) compounds. Studies on experimental animals have
found that OP pesticides have an impact on the endocrine system and a few
clinical and epidemiological studies have also shown that OPs may affect the male
hormone profile, although results are inconsistent. We have evaluated the effect
of exposure to OP pesticides, measured through urinary levels of six
dialkylphosphate (DAP) metabolites, on male hormone profile in 136 floriculture
workers from the State of Mexico and Morelos during two agricultural periods with
different degree of pesticide exposure. Generalized estimated equations (GEE)
models were developed and adjusted for several potential confounders, including
PON1 enzyme activity, as a biomarker of susceptibility, and serum levels of p,p'
DDE, a metabolite of the pesticide DDT widely used in Mexico until 1999 for
control of agricultural pests and malaria. Exposure of male floriculture workers
to OP pesticides was associated with increased serum levels of follicle
stimulating hormone (FSH) and prolactin and with decreased serum testosterone and
inhibin B levels. Among all DAPs tested, only DETP was inversely associated with
luteinizing hormone (LH). Estradiol showed a marginally significant positive
trend with DEP and DETP derivatives. In conclusion, OP pesticides may have an
impact on the endocrine function because of their potential to modify the male
hormone profile as a function of the type of pesticide used as well as the
magnitude of exposure.
PMID- 23153547
TI - New developments in the pharmacological modulation of wound healing after
glaucoma filtration surgery.
AB - Despite the advent of many new devices for glaucoma surgery, scarring is the main
cause of suboptimal pressure control and surgical failure in all forms of
surgery. The cytotoxic antimetabolites, 5-flurouracil and mitomycin C both
prolong success but with the increased risk of blinding complications. A greater
understanding of the cellular mechanisms of the wound healing response has led to
the identification and modulation of potential therapeutic targets. These include
transforming factor beta, inflammatory mediators, the acute phase protein serum
amyloid P, vascular endothelial growth factor and the matrix metallaproteinases.
While optimal drug delivery is still a major challenge, modulating these effects
either directly or through downstream signalling promises to yield anti-scarring
efficacy, while minimising side effects.
PMID- 23153548
TI - Beneficial remodeling of small saccular intracranial aneurysms after staged stent
only treatment: a case series.
AB - BACKGROUND: We evaluated the effect of stent alone treatment for small
intracranial aneurysms that were not amenable to coil embolization without prior
stent reconstruction. METHODS: This case series was conducted in the
neurosurgical service at a tertiary care hospital in Denver, Colorado. Nine
patients were electively treated for intracranial aneurysms. All patients had a
single low porosity stent reconstruction device placed across the neck of a small
intracranial aneurysm. The main outcome measures were changes in aneurysm size
and parent vessel morphology during follow-up. RESULTS: Nine patients underwent
stent alone treatment for unruptured intracranial aneurysms. The mean follow-up
period was 9.6 months (range 6-17 months). There were no cases of periprocedural
morbidity or aneurysm rupture during follow-up. All aneurysms decreased in size,
and 3 of 9 aneurysms were gone at follow-up. In addition, at follow-up all parent
vessels demonstrated straightening about the aneurysm site. CONCLUSIONS:
Beneficial remodeling with a decrease in the size of small intracranial aneurysms
may be seen after treatment with a single stent alone, particularly if the
aneurysm arises at an arterial bend or bifurcation. This phenomenon may be
related to a degree of straightening of the parent artery, improving hemodynamic
conditions about the aneurysm site.
PMID- 23153549
TI - Penumbral imaging by using perfusion computed tomography and perfusion-weighted
magnetic resonance imaging: current concepts.
AB - Perfusion computed tomography and perfusion-weighted magnetic resonance imaging
are used to evaluate the extent of the area with ischemic penumbra; however,
different parameters, algorithms, and software packages show significant
discrepancies in the size of perfusion abnormalities, which should be minimized.
Recently, cross-validation studies were performed using digital phantoms and have
elucidated the precision and reliability of various penumbral imaging techniques.
These research initiatives can promote further multicenter trials on
recanalization therapies by providing accurate inclusion/exclusion criteria for
appropriate patient selection.
PMID- 23153550
TI - Association of physical activity with the visuospatial/executive functions of the
montreal cognitive assessment in patients with vascular cognitive impairment.
AB - BACKGROUND: The Montreal Cognitive Assessment (MoCA) is more suitable than the
Mini-Mental State Examination (MMSE) for the detection of vascular cognitive
impairment. In this study, we performed a correlation analysis of MoCA/MMSE
scores with daily physical activity in patients with subcortical ischemic white
matter changes. METHODS: Ten patients (average 75.9 +/- 9.1 years old) with
extensive leukoaraiosis detected on magnetic resonance imaging underwent
cognitive testing, including the MMSE and the Japanese version of the MoCA (MoCA
J). Physical activity was monitored with the Kenz Lifecorder EX device (Suzuken,
Nagoya, Japan) to assess daily physical activity in terms of caloric expenditure,
motor activity, number of steps, and walking distance for 6 months. Correlations
of individual physical activity with total and subscale scores of MMSE/MoCA-J or
6-month interval change of MoCA-J scores were assessed. RESULTS: The total or
subscale scores of the MMSE did not correlate with any parameters of physical
activity. However, the mean number of steps and walking distance significantly
correlated with the total MoCA-J scores (r = .67 and .64, respectively) and its
visuospatial/executive subscores (r = .66 and .66, respectively). The mean
interval change of MoCA-J was + .6; those who improved number of steps (n = 4;
80.5 +/- 3.0 years of age) had significantly preserved MoCA-J scores compared to
those who did not (n = 6; 73.0 +/- 11.6 years of age; +2.0 versus - .3; P =
.016). CONCLUSIONS: These results suggest that MoCA is useful to detect a
biologically determined specific relationship between physical activity and
executive function. In addition, physical exercise, such as walking, may help
enhance cognitive function in patients with vascular cognitive impairment of
subcortical origin.
PMID- 23153551
TI - The role of small vessel disease in re-exacerbation of stroke symptoms within 24
hours after tissue plasminogen activator infusion.
AB - BACKGROUND: The purpose of this study was to examine the frequency and
characteristics of re-exacerbation of stroke symptoms within 24 hours after
tissue plasminogen activator (t-PA) infusion. METHODS: We studied consecutive
stroke patients treated with t-PA within 3 hours of onset of symptoms admitted
between October 2005 and March 2010. We divided patients into 4 groups:
improvement (IM; improvement in National Institutes of Health Stroke Scale
[NIHSS] >=4 points), unchanged (UN; no change or decline in NIHSS <4 points),
exacerbation (EX; decline in NIHSS >=4 points), and re-exacerbation (RE-EX;
decline of NIHSS >=4 points accompanied by re-exacerbation of neurologic symptoms
in NIHSS >=4 points). We compared clinical characteristics among the 4 groups.
RESULTS: Two hundred twenty-two patients (135 men; median age 76 years) were
enrolled. Sixteen of the 222 (7%) were in the RE-EX group. Small vessel disease
(SVD), hemorrhagic cerebral infarction, and reocclusion were significantly more
common among patients in the RE-EX group. SVD, hemorrhagic cerebral infarction,
and reocclusion occurred in 44%, 25%, and 13% of patients in the RE-EX group, in
9%, 22%, and 0% of patients in the EX group, in 5%, 6%, and 0% of patients in the
IM group, and in 17%, 14%, and 1% of patients in the UN group, respectively (P <
.001, P = .041, and P < .001). Multivariate logistic regression analysis revealed
that SVD was the only independent factor associated with re-exacerbation within
24 hours after t-PA infusion (odds ratio 3.52; 95% confidence interval [CI] 1.19
10.40; P = .023). CONCLUSIONS: Seven percent of patients re-exacerbated within 24
hours after intravenous infusion of t-PA. Re-exacerbation within 24 hours after t
PA infusion was strongly associated with SVD.
PMID- 23153552
TI - Epithelial to mesenchymal transition and cancer stem cell phenotypes leading to
liver metastasis are abrogated by the novel TGFbeta1-targeting peptides P17 and
P144.
AB - Colorectal cancer (CRC) frequently metastasizes to the liver, a phenomenon that
involves the participation of transforming-growth-factor-beta(1) (TGFbeta(1)).
Blockade of the protumorigenic effects elicited by TGFbeta(1) in advanced CRC
could attenuate liver metastasis. We aimed in the present study to assess the
antimetastatic effect of TGFbeta(1)-blocking peptides P17 and P144, and to study
mechanisms responsible for this activity in a mouse model. Colon adenocarcinoma
cells expressing luciferase were pretreated with TGFbeta(1) (Mc38-luc(TGFbeta1)
cells), injected into the spleen of mice and monitored for tumor development.
TGFbeta(1) increased primary tumor growth and liver metastasis, whereas systemic
treatment of mice with either P17 or P144 significantly reduced tumor burden
(p<0.01). In metastatic nodules, mitotic/apoptotic ratio, mesenchymal traits and
angiogenesis (evaluated by CD-31, as well as circulating endothelial and
progenitor cells) induced by TGFbeta(1) were consistently reduced following
injection of peptides. In vitro experiments revealed a direct effect of
TGFbeta(1) in Mc38 cells, which resulted in activation of Smad2, Smad3 and
Smad1/5/8, and increased invasion and transendothelial migration, whereas
blockade of TGFbeta(1)-signaling reverted these features. Because TGFbeta(1)
mediated epithelial-mesenchymal transition (EMT) has been suggested to induce a
cancer stem cell (CSC) phenotype, we analyzed the ability of this cytokine to
induce tumorsphere formation and the expression of CSC markers. In TGFbeta(1)
treated cells, tumorspheres were enriched in CD44 and SOX2, which were diminished
in the presence of P17. Our data provide a preclinical rationale to evaluate P17
and P144 as potential therapeutic options for the treatment of metastatic CRC.
PMID- 23153553
TI - Directional cell migration in an extracellular pH gradient: a model study with an
engineered cell line and primary microvascular endothelial cells.
AB - Extracellular pH (pH(e)) gradients are characteristic of tumor and wound
environments. Cell migration in these environments is critical to tumor
progression and wound healing. While it has been shown previously that cell
migration can be modulated in conditions of spatially invariant acidic pH(e) due
to acid-induced activation of cell surface integrin receptors, the effects of
pH(e) gradients on cell migration remain unknown. Here, we investigate cell
migration in an extracellular pH(e) gradient, using both model alpha(v)beta(3)
CHO-B2 cells and primary microvascular endothelial cells. For both cell types, we
find that the mean cell position shifts toward the acidic end of the gradient
over time, and that cells preferentially polarize toward the acidic end of the
gradient during migration. We further demonstrate that cell membrane protrusion
stability and actin-integrin adhesion complex formation are increased in acidic
pH(e), which could contribute to the preferential polarization toward acidic
pH(e) that we observed for cells in pH(e) gradients. These results provide the
first demonstration of preferential cell migration toward acid in a pH(e)
gradient, with intriguing implications for directed cell migration in the tumor
and wound healing environments.
PMID- 23153554
TI - PGE2 suppresses NK activity in vivo directly and through adrenal hormones:
effects that cannot be reflected by ex vivo assessment of NK cytotoxicity.
AB - Surgery can suppress in vivo levels of NK cell cytotoxicity (NKCC) through
various mechanisms, including catecholamine-, glucocorticoid (CORT)-, and
prostaglandin (PG)-mediated responses. However, PGs are synthesized locally
following tissue damage, driving proinflammatory and CORT responses, while their
systemic levels are often unaffected. Thus, we herein studied the role of adrenal
factors in mediating in vivo effects of PGs on NKCC, using adrenalectomized and
sham-operated F344 rats subjected to surgery or PGE(2) administration. In vivo
and ex vivo approaches were employed, based on intravenous administration of the
NK-sensitive MADB106 tumor line, and based on ex vivo assessment of YAC-1 and
MADB106 target-line lysis. Additionally, in vitro studies assessed the kinetics
of the impact of epinephrine, CORT, and PGE(2) on NKCC. The results indicated
that suppression of NKCC by epinephrine and PGE(2) are short lasting, and cannot
be evident when these compounds are removed from the in vitro assay milieu, or in
the context of ex vivo assessment of NKCC. In contrast, the effects of CORT are
long-lasting and are reflected in both conditions even after its removal.
Marginating-pulmonary NKCC was less susceptible to suppression than circulating
NKCC, when tested against the xenogeneic YAC-1 target line, but not against the
syngeneic MADB106 line, which seems to involve different cytotoxicity mechanisms.
Overall, these findings indicate that elevated systemic PG levels can directly
suppress NKCC in vivo, but following laparotomy adrenal hormones mediate most of
the effects of endogenously-released PGs. Additionally, the ex vivo approach
seems limited in reflecting the short-lasting NK-suppressive effects of
catecholamines and PGs.
PMID- 23153555
TI - Housing of growing rabbits in individual, bicellular and collective cages: growth
performance, carcass traits and meat quality.
AB - During growth (from 27 to 75 days of age), 384 rabbits were kept in different
types of wire-net cages: 72 individual cages (72 rabbits; 10 animals/m2), 48
bicellular cages (96 rabbits; 2 rabbits/cage; 18 animals/m2) and 24 collective
cages (216 rabbits; 9 rabbits/cage; 18 animals/m2). The rabbits housed in
individual cages showed higher daily weight gain both during the fattening period
(from 52 to 75 days of age) and during the whole period of growth (43.0 v. 41.8
and 41.5 g/day; P < 0.05), and they had a higher final live weight at 75 days of
age (2678 v. 2619 and 2602 g; P < 0.05) compared with the rabbits in the
bicellular and collective cages, respectively. Rabbits in individual cages
ingested more feed (133 v. 127 and 126 g/day; P < 0.01), but the feed conversion
did not differ significantly among rabbits housed in the three types of cages. At
slaughter, the carcass traits and meat quality were weakly affected by the
housing system. The transport losses were higher in rabbits kept in individual
and bicellular cages compared with those reared in collective cages (3.1% and
2.9% v. 2.2%; P < 0.01). In rabbits kept in individual cages, the hind leg muscle
to bone ratio was higher (6.35 v. 6.19 and 5.91; P < 0.05) compared with the
bicellular and collective cages, respectively. The pH and colour of the
longissimus lumborum did not change with the housing system, while the b* index
of the biceps femoris was lower (3.04 and 3.32 v. 4.26; P < 0.001) in the rabbits
kept in individual and bicellular cages, respectively, than in those kept in
collective cages. In conclusion, the rabbits housed in individual cages showed
higher daily growth than rabbits kept in bicellular or collective cages, but they
had a similar feed conversion and carcass quality. Differently, neither in vivo
performance nor slaughter results differed among the rabbits kept in bicellular
cages or in collective cages. The meat colour may be affected by the housing
system, but to an extent that is hardly perceivable by the final consumer.
PMID- 23153556
TI - Low molecular weight heparins copies: are they considered to be generics or
biosimilars?
AB - The protection rights of low molecular weight heparins (LMWHs) are expired or are
expiring, so the extent and nature of the studies required to obtain a market
authorization for LMWH copies represents a hot topic. FDA classifies LMWHs as
semisynthetic drugs and their copies as generics whereas the EMA views them as
biological medicines and consequently their copies as biosimilars. Consequently,
FDA requires only in vivo pharmacodynamic studies, while EMA requires also
clinical trials. The current work reviews the chemical composition and
therapeutic indications of LMWHs available in the EU and USA markets to discuss
the two different approaches. Because LMWHs show a high intrinsic variability and
a complete characterization is not viable, a conservative approach is desirable.
PMID- 23153557
TI - Alpha B-crystallin prevents the arrhythmogenic effects of particulate matter
isolated from ambient air by attenuating oxidative stress.
AB - Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is activated by
particulate matter (PM) isolated from ambient air and linked to prolonged
repolarization and cardiac arrhythmia. We evaluated whether alpha B-crystallin
(CryAB), a heat shock protein, could prevent the arrhythmogenic effects of PM by
preventing CaMKII activation. CryAB was delivered into cardiac cells using a TAT
protein transduction domain (TAT-CryAB). ECGs were measured before and after
tracheal exposure of diesel exhaust particles (DEP) and each intervention in
adult Sprague-Dawley rats. After endotracheal exposure of DEP (200 MUg/mL for 30
minutes, n=11), QT intervals were prolonged from 115+/-14 ms to 144+/-20 ms
(p=0.03), and premature ventricular contractions were observed more frequently
(0% vs. 44%) than control (n=5) and TAT-Cry (n=5). However, DEP-induced
arrhythmia was not observed in TAT-CryAB (1 mg/kg) pretreated rats (n=5). In
optical mapping of Langendorff-perfused rat heats, compared with baseline, DEP
infusion of 12.5 MUg/mL (n=12) increased apicobasal action potential duration
(APD) differences from 2+/-6 ms to 36+/-15 ms (p<0.001), APD restitution slope
from 0.26+/-0.07 to 1.19+/-0.11 (p<0.001) and ventricular tachycardia (VT) from
0% to 75% (p<0.001). DEP infusion easily induced spatially discordant alternans.
However, the effects of DEP were prevented by TAT-CryAB (1mg/kg, n=9). In rat
myocytes, while DEP increased reactive oxygen species (ROS) generation and
phosphated CaMKII, TAT-CryAB prevented these effects. In conclusion, CryAB, a
small heat shock protein, might prevent the arrhythmogenic effects of PM by
attenuating ROS generation and CaMKII activation.
PMID- 23153558
TI - Gallic acid inhibits gastric cancer cells metastasis and invasive growth via
increased expression of RhoB, downregulation of AKT/small GTPase signals and
inhibition of NF-kappaB activity.
AB - Our previous study demonstrated the therapeutic potential of gallic acid (GA) for
controlling tumor metastasis through its inhibitory effect on the motility of AGS
cells. A noteworthy finding in our previous experiment was increased RhoB
expression in GA-treated cells. The aim of this study was to evaluate the role of
RhoB expression on the inhibitory effects of GA on AGS cells. By applying the
transfection of RhoB siRNA into AGS cells and an animal model, we tested the
effect of GA on inhibition of tumor growth and RhoB expression. The results
confirmed that RhoB-siRNA transfection induced GA to inhibit AGS cells' invasive
growth involving blocking the AKT/small GTPase signals pathway and inhibition of
NF-kappaB activity. Finally, we evaluated the effect of GA on AGS cell metastasis
by colonization of tumor cells in nude mice. It showed GA inhibited tumor cells
growth via the expression of RhoB. These data support the inhibitory effect of GA
which was shown to inhibit gastric cancer cell metastasis and invasive growth via
increased expression of RhoB, downregulation of AKT/small GTPase signals and
inhibition of NF-kappaB activity. Thus, GA might be a potential agent in treating
gastric cancer.
PMID- 23153559
TI - Detection of genotoxic and non-genotoxic carcinogens in Xpc(-/-)p53(+/-) mice.
AB - An accurate assessment of the carcinogenic potential of chemicals and
pharmaceutical drugs is essential to protect humans and the environment.
Therefore, substances are extensively tested before they are marketed to the
public. Currently, the rodent two-year bioassay is still routinely used to assess
the carcinogenic potential of substances. However, over time it has become clear
that this assay yields false positive results and also has several economic and
ethical drawbacks including the use of large numbers of animals, the long
duration, and the high cost. The need for a suitable alternative assay is
therefore high. Previously, we have proposed the Xpa*p53 mouse model as a very
suitable alternative to the two-year bioassay. We now show that the Xpc*p53 mouse
model preserves all the beneficial traits of the Xpa*p53 model for sub-chronic
carcinogen identification and can identify both genotoxic and non-genotoxic
carcinogens. Moreover, Xpc*p53 mice appear to be more responsive than Xpa*p53
mice towards several genotoxic and non-genotoxic carcinogens. Furthermore,
Xpc*p53 mice are far less sensitive than Xpa*p53 mice for the toxic activity of
DNA damaging agents and as such clearly respond in a similar way as wild type
mice do. These advantageous traits of the Xpc*p53 model make it a better
alternative for in vivo carcinogen testing than Xpa*p53. This pilot study
suggests that Xpc*p53 mice are suited for routine sub-chronic testing of both
genotoxic and non-genotoxic carcinogens and as such represent a suitable
alternative to possibly replace the murine life time cancer bioassay.
PMID- 23153561
TI - Use of face masks in a primary care outpatient setting in Hong Kong: Knowledge,
attitudes and practices.
AB - OBJECTIVES: To assess if a knowledge gap exists in the correct use of face masks,
and to explore the correlations between knowledge, attitudes and practices
regarding the use of face masks among outpatients and their caregivers in an
outpatient clinic in Hong Kong. STUDY DESIGN: Cross-sectional study. METHODS:
Outpatients and their caregivers who were present at an outpatient setting in
Hong Kong were invited to participate in this survey. All participants were asked
to complete a self-administered closed-ended questionnaire about their knowledge,
attitudes and practices regarding the use of face masks. Data were described
using descriptive statistics and correlation coefficients. RESULTS: Among the 399
respondents, 52% knew the correct steps in wearing a face mask, and their
attitudes toward face masks were generally positive. Further analyses showed that
respondents were more likely to wear a face mask at a clinic than in a public
place or at home. Moreover, respondents were more likely to wear a face mask to
protect others against influenza-like illness (ILI) than for self-protection.
There was low to moderate correlation between attitudes and practices
(correlation coefficient 0.26, P < 0.05). CONCLUSIONS: This study identified a
knowledge gap in the correct use of face masks among outpatients and their
caregivers; attitudes and practices regarding the use of face masks were
generally positive, but correlation was not high. It is recommended that public
health education campaigns should tailor efficient programmes to combat ILI
transmission among outpatient clinic populations by improving knowledge about the
correct use of face masks.
PMID- 23153560
TI - Sulforaphane is not an effective antagonist of the human pregnane X-receptor in
vivo.
AB - Sulforaphane (SFN), is an effective in vitro antagonist of ligand activation of
the human pregnane and xenobiotic receptor (PXR). PXR mediated CYP3A4 up
regulation is implicated in adverse drug-drug interactions making identification
of small molecule antagonists a desirable therapeutic goal. SFN is not an
antagonist to mouse or rat PXR in vitro; thus, normal rodent species are not
suitable as in vivo models for human response. To evaluate whether SFN can
effectively antagonize ligand activation of human PXR in vivo, a three-armed,
randomized, crossover trial was conducted with 24 healthy adults. The potent PXR
ligand - rifampicin (300mg/d) was given alone for 7days in arm 1, or in daily
combination with 450MUmol SFN (Broccoli Sprout extract) in arm 2; SFN was given
alone in arm 3. Midazolam as an in vivo phenotype marker of CYP3A was
administered before and after each treatment arm. Rifampicin alone decreased
midazolam AUC by 70%, indicative of the expected increase in CYP3A4 activity. Co
treatment with SFN did not reduce CYP3A4 induction. Treatment with SFN alone also
did not affect CYP3A4 activity in the cohort as a whole, although in the subset
with the highest basal CYP3A4 activity there was a statistically significant
increase in midazolam AUC (i.e., decrease in CYP3A4 activity). A parallel study
in humanized PXR mice yielded similar results. The parallel effects of SFN
between humanized PXR mice and human subjects demonstrate the predictive value of
humanized mouse models in situations where species differences in ligand-receptor
interactions preclude the use of a native mouse model for studying human ligand
receptor pharmacology.
PMID- 23153562
TI - Prevalence of overweight/obesity and its association with sedentary behavior in
children.
AB - OBJECTIVE: The aim of this study was to determine the prevalence of overweight
and obesity in children in the northeast region of Portugal, and to examine its
association with sedentary behavior. METHODS: Data were collected on 1786
children (907 boys, 879 girls) aged 6 to 13 years. Body mass index was calculated
from measured height and weight (weight in kg/height in m squared). Overweight
and obesity were determined using the International Obesity Task Force cutoff
values. Sedentary behavior was assessed based on means of transport to and from
school and time spent watching TV and playing video games (TVPC). RESULTS: The
prevalences of overweight and obesity were 22.6% and 9.4% respectively. The
differences between the sexes for both overweight and obesity were not
significant. Most of the children (78.4%) go to school by car. Boys spend more
time on TVPC than girls, both on weekdays and on weekends. The logistic
regression model indicated a significant effect of 1.5 hours of TVPC by boys
during weekdays (OR=0.246; p=0.015). Boys who spent less than 1.5 hours on
weekdays on TVPC were 75.4% less likely to be overweight than those who spent
more than 1.5 hours. CONCLUSION: The prevalence of overweight and obesity was
32%. Only 12.2% of the children spend less than 1.5 hours on TVPC. Boys who spend
less than 1.5 hours on TVPC are 75.4% less likely to be overweight/obese than
those who spend more than 1.5 hours.
PMID- 23153563
TI - The two-cell embryo--two sides of the same coin?
PMID- 23153564
TI - Seminal plasma induces prostaglandin-endoperoxide synthase (PTGS) 2 expression in
immortalized human vaginal cells: involvement of semen prostaglandin E2 in PTGS2
upregulation.
AB - Inflammation of the cervicovaginal mucosa is considered a risk factor for HIV
infection in heterosexual transmission. In this context, seminal plasma (SP) may
play an important role that is not limited to being the main carrier for the
virions. It is known that SP induces an inflammatory reaction in the cervix
called postcoital leukocytic reaction, which has been associated with promotion
of fertility. The mechanisms by which SP triggers this reaction, however, have
not been clearly established. Previously we reported the expression of
prostaglandin-endoperoxide synthase 2 (PTGS2), also known as cyclooxygenase 2
(COX-2), in human vaginal cells in response to toll-like receptor (TLR) ligands
and other proinflammatory stimuli. In this study, we demonstrate that SP induces
transcriptional and translational increase of COX-2 expression in human vaginal
cells and cervicovaginal tissue explants. Furthermore, SP potentiates vaginal
PTGS2 expression induced by other proinflammatory stimulants, such as TLR ligands
and a vaginal mucosal irritant (nonoxynol-9) in a synergistic manner. SP-induced
PTGS2 expression is mediated by intracellular signaling pathways involving MAPKs
and NF-kappaB. Using fractionation and functional analysis, seminal prostaglandin
(PG)-E(2) was identified as a one of the major factors in PTGS2 induction. Given
the critical role of this PG-producing enzyme in mucosal inflammatory processes,
the finding that SP induces and potentiates the expression of PTGS2 in
cervicovaginal cells and tissues has mechanistic implications for the role of SP
in fertility-associated mucosal leukocytic reaction and its potential HIV
infection-enhancing effect.
PMID- 23153566
TI - The role of maternal-fetal cholesterol transport in early fetal life: current
insights.
AB - The importance of maternal cholesterol as an exogenous cholesterol source for the
growing embryo was first reported in studies of Smith-Lemli-Opitz syndrome.
Although most of the fetus's cholesterol is synthesized by the fetus itself,
there is now growing evidence that during the first weeks of life, when most
organs develop, the fetus largely depends on maternal cholesterol as its
cholesterol source. The maternal-fetal cholesterol transport mechanism, by
transporters in both the yolk sac and placenta, is becoming better understood.
This minireview summarizes current insights on maternal-fetal cholesterol
transport based on in vitro and in vivo studies. As the prevalence of maternal
diseases, such as diabetes, obesity, and the metabolic syndrome that adversely
affect maternal cholesterol levels, is now rapidly reaching epidemic proportions,
we urgently need to determine the impact of these maternal conditions on the
developing human fetus.
PMID- 23153565
TI - Enhanced genetic integrity in mouse germ cells.
AB - Genetically based diseases constitute a major human health burden, and de novo
germline mutations represent a source of heritable genetic alterations that can
cause such disorders in offspring. The availability of transgenic rodent systems
with recoverable, mutation reporter genes has been used to assess the occurrence
of spontaneous point mutations in germline cells. Previous studies using the lacI
mutation reporter transgenic mouse system showed that the frequency of
spontaneous mutations is significantly lower in advanced male germ cells than in
somatic cell types from the same individuals. Here we used this same mutation
reporter transgene system to show that female germ cells also display a mutation
frequency that is lower than that in corresponding somatic cells and similar to
that seen in male germ cells, indicating this is a common feature of germ cells
in both sexes. In addition, we showed that statistically significant differences
in mutation frequencies are evident between germ cells and somatic cells in both
sexes as early as mid-fetal stages in the mouse. Finally, a comparison of the
mutation frequency in a general population of early type A spermatogonia with
that in a population enriched for Thy-1-positive spermatogonia suggests there is
heterogeneity among the early spermatogonial population such that a subset of
these cells are predestined to form true spermatogonial stem cells. Taken
together, these results support the disposable soma theory, which posits that
genetic integrity is normally maintained more stringently in the germ line than
in the soma and suggests that this is achieved by minimizing the initial
occurrence of mutations in early germline cells and their subsequent gametogenic
progeny relative to that in somatic cells.
PMID- 23153567
TI - Informal payments for maternity health services in public hospitals in Greece.
AB - BACKGROUND: Private health expenditure for consuming maternity health services
has been identified as an issue within public hospitals. AIM: To estimate level
of private health expenditure, in the form of informal payments, for maternal
services in public hospitals in Greece. METHODS: The study population consisted
of 160 women who had recently given birth in three provincial general hospitals
and one general hospital in Athens. A three-part questionnaire was developed in
order to collect financial information regarding the use of public obstetrics
services in Greece. RESULTS: The mean age of respondents was 29.5 (+/-5.6) years.
There was a high rate of informal payments with 74.4% of women involved in
informal transactions. Mean total private payments were ?1549 (+/-992),
representing 7.9% of the mean annual per capita income in Greece. Mean informal
payment was ?848 (+/-714). For 56.3% of the respondents, it was at the
obstetrician's request, on top of formal payment of ?701 (+/-1351). Total
informal payments were higher for women who gave birth in Athens (p<0.001), for
Greek women compared to non Greek (p<0.001) and for deliveries that were
conducted by women's personal obstetrician (p=0.001). CONCLUSION: There is a
large black economy in the field of obstetric services, as 74.4% of women who
used public maternity services had to pay under-the-table payments corresponding
approximately to the net salary of an intern physician. There is a need for the
state to adopt innovative strategies and mechanisms in order to reduce informal
payments for obstetric services in the public sector.
PMID- 23153568
TI - Mobility of health professionals pre and post 2004 and 2007 EU enlargements:
evidence from the EU project PROMeTHEUS.
AB - BACKGROUND: EU enlargement has facilitated the mobility of EU citizens, including
health professionals, from the 2004 and 2007 EU accession states. Fears have been
raised about a mass exodus of health professionals and the consequences for the
operation of health systems. However, to date a systematic analysis of the EU
enlargement's effects on the mobility of health professionals has been lacking.
The aim of this article is to shed light on the changes in the scale of movement,
trends and directions of flows pre and post 2004 and 2007 EU enlargements.
METHODS: The study follows a pan-European secondary data analysis to (i)
quantitatively and (ii) qualitatively analyse mobility before and after the EU
enlargement. (i) The secondary data analysis covers 34 countries (including all
EU Member States). (ii) Data were triangulated with the findings of 17 country
case studies to qualitatively assess the effects of enlargement on health
workforce mobility. RESULTS: The stock of health professionals from the new (EU
12) into the old EU Member States (EU-15) have increased following EU accession.
The stock of medical doctors from the EU-12 in the EU-15 countries has more than
doubled between 2003 and 2007. The available data suggest the same trend for
dentists. The extremely limited data for nurses show that the stock of nurses
has, in contrast, only slightly increased. However, while no reliable data is
available evidence suggests that the number of undocumented or self-employed
migrant nurses in the home-care sector has significantly increased. Health
professionals trained in the EU-12 are becoming increasingly important in
providing sufficient health care in some destination countries and regions facing
staff shortages. CONCLUSION: A mass exodus of health professionals has not taken
place after the 2004 and 2007 EU enlargements. The estimated annual outflows from
the EU-12 countries have rarely exceeded 3% of the domestic workforce. This is
partly due to labour market restrictions in the destination countries, but also
to improvements in salaries and working conditions in some source countries. The
overall mobility of health professionals is hence relatively moderate and in line
with the overall movement of citizens within the EU. However, for some countries
even losing small numbers of health professionals can have impacts in underserved
regions.
PMID- 23153569
TI - Parent-youth discordance about youth-witnessed violence: associations with trauma
symptoms and service use in an at-risk sample.
AB - OBJECTIVE: Studies have consistently demonstrated a lack of agreement between
youth and parent reports regarding youth-witnessed violence. However, little is
known about whether disagreement is associated with poorer outcomes and less
utilization of mental health services. The purpose of the current study was to
examine disagreement among youth and parents about youth witnessed violence, and
determine whether concordance predicted trauma symptoms and recognition of need
and receipt of counseling services. METHODS: Concordance about youth-witnessed
violence was examined in 766 dyads from the Longitudinal Studies of Child Abuse
and Neglect (LONGSCAN). Youth participants self-reported trauma symptoms,
caregivers indicated youth need for and receipt of services. Both youth and
parents provided information about youth-witnessed violence exposure in the last
year. RESULTS: Results showed youth and caregivers differed significantly about
youth-witnessed violence. Specifically, 42% of youth reported youth-witnessed
violence, compared to only 15% of parents. For those parents who reported youth
witnessed violence, only 29% reported an identified need for services and only
17% reported the youth had received any mental health services. Concordance
between parent-youth dyads was associated with greater identified need for
services but was not associated with the use of counseling services or trauma
symptoms. CONCLUSIONS: Youth who reported witnessing violence reported more
frequent trauma symptoms regardless of concordance. Parents from dyads in which
both informants reported youth-witnessed violence were more likely to endorse
need for, but not receipt of counseling services. Given this association between
youth-witnessed violence and mental health problems, more work is needed to
identify barriers to concordance as well as service utilization.
PMID- 23153570
TI - Dexamethasone administration to the neonatal rat results in neurological
dysfunction at the juvenile stage even at low doses.
AB - Dexamethasone (DEX), a synthetic glucocorticoid, has been widely used to prevent
the development of a variety of poor health conditions in premature infants
including chronic lung disease, inflammation, circulatory failure, and shock.
Although there are some reports of neurologic complications related to DEX
exposure, its full effects on the premature brain have not been examined in
detail. To investigate the effects of DEX on neural development, we first
administered low doses (0.2 mg/kg bodyweight or less) of the glucocorticoid to
neonatal rats on a daily basis during the first postnatal week and examined
subsequent behavioral alterations at the juvenile stage. DEX-treated rats
exhibited not only a significant reduction in both somatic and brain weights but
also learning disabilities as revealed in the shuttle avoidance test. The
hippocampi of DEX-treated rats displayed a high apoptotic and a low mitotic cell
density compared to control rats on day 7 after birth. In a subsequent
experiment, neural stem/progenitor cells were cultured in the presence of DEX for
6 days. The glucocorticoid inhibited cell growth without an increase in cell
death. These results suggest that administration of DEX to premature infants
induces neurological dysfunction via inhibition of the proliferation of neural
stem/progenitor cells.
PMID- 23153571
TI - Analytical measurement and clinical relevance of vitamin D(3) C3-epimer.
AB - With an ever-increasing clinical interest in vitamin D insufficiency, numerous
automated immunoassays, protein binding assays, and in-house LC-MS/MS methods are
being developed for the quantification of 25-hydroxyvitamin D(3) (25(OH)D(3)).
Recently, LC-MS/MS methods have identified an epimeric form of 25(OH)D(3) that
has been shown to contribute significantly to 25(OH)D(3) concentration,
particularly in infant populations. This review describes the metabolic pathway
and physiological functions of 3-epi-vitamin D, compares the capability of
various 25(OH)D(3) methods to detect the epimer, and highlights recent
publications quantifying 3-epi-25(OH)D(3) in infant, pediatric, and adult
populations. In total, this review summarizes the information necessary for
clinicians and laboratorians to decide whether or not to report/consider the C3
epimer in the analysis and clinical assessment of vitamin D status.
PMID- 23153572
TI - Subpopulation-proteomics in prokaryotic populations.
AB - Clonal microbial cells do not behave in an identical manner and form
subpopulations during cultivation. Besides varying micro-environmental
conditions, cell inherent features like cell cycle dependent localization and
concentration of regulatory proteins as well as epigenetic properties are well
accepted mechanisms creating cell heterogeneity. Another suspected reason is
molecular noise on the transcriptional and translational level. A promising tool
to unravel reasons for cell heterogeneity is the combination of cell sorting and
subpopulation proteomics. This review summarizes recent developments in
prokaryotic single-cell analytics and provides a workflow for selection of single
cells, low cell number mass spectrometry, and proteomics evaluation. This
approach is useful for understanding the dependency of individual cell decisions
on inherent protein profiles.
PMID- 23153573
TI - Effect of application mode on interfacial morphology and chemistry between
dentine and self-etch adhesives.
AB - OBJECTIVE: To investigate the influence of application mode on the interfacial
morphology and chemistry between dentine and self-etch adhesives with different
aggressiveness. METHODS: The occlusal one-third of the crown was removed from un
erupted human third molars, followed by abrading with 600 grit SiC under water.
Rectangular dentine slabs were prepared by sectioning the tooth specimens
perpendicular to the abraded surfaces. The obtained dentine slabs were treated
with one of the two one-step self-etch adhesives: Adper Easy Bond (AEB, pH~2.5)
and Adper Prompt L-Pop (APLP, pH~0.8) with (15s, active application) or without
(15s, inactive application) agitation. The dentine slabs were fractured and the
exposed adhesive/dentine (A/D) interfaces were examined with micro-Raman
spectroscopy and scanning electron microscopy (SEM). RESULTS: The interfacial
morphology, degree of dentine demineralization (DD) and degree of conversion (DC)
of the strong self-etch adhesive APLP showed more significant dependence on the
application mode than the mild AEB. APLP exhibited inferior bonding at the A/D
interface if applied without agitation, evidenced by debonding from the dentine
substrate. The DDs and DCs of the APLP with agitation were higher than those of
without agitation in the interface, in contrast to the comparable DD and DC
values of two AEB specimen groups with different application modes. Raman
spectral analysis revealed the important role of chemical interaction between
acid monomers of self-etch adhesives and dentine in the above observations.
CONCLUSION: The chemical interaction with dentine is especially important for
improving the DC of the strong self-etching adhesive at the A/D interface.
Agitation could benefit polymerization efficacy of the strong self-etch adhesive
through enhancing the chemical interaction with tooth substrate.
PMID- 23153574
TI - Epigenetics and miRNAs in the diagnosis and treatment of multiple sclerosis.
AB - The risk of developing multiple sclerosis (MS) depends on both genetic and
environmental factors. Although the genetic susceptibility to MS has been
investigated in great detail, reports describing epigenetic changes in the
context of MS have only recently appeared. Epigenetic changes to DNA influence
gene expression without altering the underlying DNA sequence. DNA methylation,
histone modification, and miRNA-associated silencing are the three most important
epigenetic mechanisms that influence gene expression. In this review, we
summarize recent studies investigating epigenetic changes and miRNA as biomarkers
for diagnosing MS and predicting disease course or treatment response. We also
discuss how the current studies address important clinical questions and how
future studies could be designed to best inform clinical practice.
PMID- 23153575
TI - CXCR7 impact on CXCL12 biology and disease.
AB - It is known that the chemokine receptor CXCR7 (RDC1) can be engaged by both
chemokines CXCL12 (SDF-1) and CXCL11 (I-TAC), but the exact expression pattern
and function of CXCR7 is controversial. CXCR7 expression seems to be enhanced
during pathological inflammation and tumor development, and emerging data suggest
this receptor is an attractive therapeutic target for autoimmune diseases and
cancer. CXCR7/CXCR4 heterodimerization, beta-arrestin-mediated signaling, and
modulation of CXCL12 responsiveness by CXCR7 suggest that the monogamous
CXCR4/CXCL12 signaling axis is an oversimplified model that needs to be
revisited. Consequently, research into CXCR7 biology is of great interest and
further studies are warranted. This review summarizes recent findings about the
CXCR7 receptor and analyses its impact on understanding the roles of CXCL12
biology in health and disease.
PMID- 23153576
TI - Substantia nigra vulnerability after a single moderate diffuse brain injury in
the rat.
PMID- 23153577
TI - Hydrogen sulfide inhibits preoptic prostaglandin E2 production during
endotoxemia.
AB - Hydrogen sulfide (H(2)S) is a gaseous neuromodulator endogenously produced in the
brain by the enzyme cystathionine beta-synthase (CBS). We tested the hypothesis
that H(2)S acts within the anteroventral preoptic region of the hypothalamus
(AVPO) modulating the production of prostaglandin (PG) E(2) (the proximal
mediator of fever) and cyclic AMP (cAMP). To this end, we recorded deep body
temperature (Tb) of rats before and after pharmacological modulation of the CBS
H(2)S system combined or not with lipopolysaccharide (LPS) exposure, and measured
the levels of H(2)S, cAMP, and PGE(2) in the AVPO during systemic inflammation.
Intracerebroventricular (icv) microinjection of aminooxyacetate (AOA, a CBS
inhibitor; 100 pmol) did not affect basal PGE(2) production and Tb, but enhanced
LPS-induced PGE(2) production and fever, indicating that endogenous H(2)S plays
an antipyretic role. In agreement, icv microinjection of a H(2)S donor (Na(2)S;
260 nmol) reduced the LPS-induced PGE(2) production and fever. Interestingly, we
observed that the AVPO levels of H(2)S were decreased following the
immunoinflammatory challenge. Furthermore, fever was associated with decreased
levels of AVPO cAMP and increased levels of AVPO PGE(2). The LPS-induced
decreased levels of cAMP were reduced to a lesser extent by the H(2)S donor. The
LPS-induced PGE(2) production was potentiated by AOA (the CBS inhibitor) and
inhibited by the H(2)S donor. Our data are consistent with the notion that the
gaseous messenger H(2)S synthesis is downregulated during endotoxemia favoring
PGE(2) synthesis and lowering cAMP levels in the preoptic hypothalamus.
PMID- 23153579
TI - Ischemic conditioning protects the rat retina in an experimental model of early
type 2 diabetes.
AB - Diabetic retinopathy is a leading cause of acquired blindness in adults, mostly
affected by type 2 diabetes mellitus (T2DM). We have developed an experimental
model of early T2DM in adult rats which mimics some features of human T2DM at its
initial stages, and provokes significant retinal alterations. We investigated the
effect of ischemic conditioning on retinal changes induced by the moderate
metabolic derangement. For this purpose, adult male Wistar rats received a
control diet or 30% sucrose in the drinking water, and 3 weeks after this
treatment, animals were injected with vehicle or streptozotocin (STZ, 25mg/kg).
Retinal ischemia was induced by increasing intraocular pressure to 120 mm Hg for
5 min; this maneuver started 3 weeks after vehicle or STZ injection and was
weekly repeated in one eye, while control eyes were submitted to a sham
procedure. Fasting and postprandial glycemia, and glucose, and insulin tolerance
tests were analyzed. At 12 weeks of treatment, animals which received a sucrose
enriched diet and STZ showed significant differences in metabolic tests, as
compared with control groups. Brief ischemia pulses in one eye and a sham
procedure in the contralateral eye did not affect glucose metabolism in control
or diabetic rats. Ischemic pulses reduced the decrease in the electroretinogram a
wave, b-wave, and oscillatory potential amplitude, and the increase in retinal
lipid peroxidation, NOS activity, TNFalpha, Muller cells glial fibrillary acidic
protein, and vascular endothelial growth factor levels observed in diabetic
animals. In addition, ischemic conditioning prevented the decrease in retinal
catalase activity induced by T2DM. These results indicate that induction of
ischemic tolerance could constitute a fertile avenue for the development of new
therapeutic strategies to treat diabetic retinopathy associated with T2DM.
PMID- 23153578
TI - Expression of human E46K-mutated alpha-synuclein in BAC-transgenic rats
replicates early-stage Parkinson's disease features and enhances vulnerability to
mitochondrial impairment.
AB - Parkinson's disease (PD), the second most common neurodegenerative disorder, is
etiologically heterogeneous, with most cases thought to arise from a combination
of environmental factors and genetic predisposition; about 10% of cases are
caused by single gene mutations. While neurotoxin models replicate many of the
key behavioral and neurological features, they often have limited relevance to
human exposures. Genetic models replicate known disease-causing mutations, but
are mostly unsuccessful in reproducing major features of PD. In this study, we
created a BAC (bacterial artificial chromosome) transgenic rat model of PD
expressing the E46K mutation of alpha-synuclein, which is pathogenic in humans.
The mutant protein was expressed at levels ~2-3-fold above endogenous alpha
synuclein levels. At 12 months of age, there was no overt damage to the
nigrostriatal dopamine system; however, (i) alterations in striatal
neurotransmitter metabolism, (ii) accumulation and aggregation of alpha-synuclein
in nigral dopamine neurons, and (iii) evidence of oxidative stress suggest this
model replicates several preclinical features of PD. Further, when these animals
were exposed to rotenone, a mitochondrial toxin linked to PD, they showed
heightened sensitivity, indicating that alpha-synuclein expression modulates the
vulnerability to mitochondrial impairment. We conclude that these animals are
well-suited to examination of gene-environment interactions that are relevant to
PD.
PMID- 23153580
TI - Magnetic resonance imaging characterization of different experimental autoimmune
encephalomyelitis models and the therapeutic effect of glatiramer acetate.
AB - The roles of inflammation and degeneration as well as of gray matter
abnormalities in multiple sclerosis (MS) and its animal model experimental
autoimmune encephalomyelitis (EAE) are controversial. We analyzed the
pathological manifestations in two EAE models, the chronic oligodendrocyte
glycoprotein (MOG)-induced versus the relapsing-remitting proteolipid protein
(PLP)-induced, along the disease progression, using advanced magnetic resonance
imaging (MRI) parameters. The emphasis of this study was the overall assessment
of the whole brain by histogram analysis, as well as the detection of specific
affected regions by voxel based analysis (VBA) using quantitative T2,
magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI). Brains of
EAE-inflicted mice from both models revealed multiple white and gray matter areas
with significant changes from naive mice for all MRI parameters. Ventricle
swelling was more characteristic to the PLP-induced model. Decreased MTR values
and increased apparent diffusion coefficient (ADC) were observed mainly in MOG
induced EAE, indicative of macromolecular loss and structural CNS damage
involvement in the chronic disease. The MS drug glatiramer acetate (GA), applied
either as prevention or therapeutic treatment, affected all the MRI pathological
manifestations, resulting in reduced T2 values and ventricle volume, elevated MTR
and decreased ADC, in comparison to untreated EAE-inflicted mice. In accord,
immunohistochemical analysis indicated less histological damage and higher amount
of proliferating oligodendrocyte progenitor cells after GA treatment. The higher
brain tissue integrity reflected by the MRI parameters on the level of the whole
brain and in specific regions supports the in situ anti-inflammatory and
neuroprotective consequences of GA treatment.
PMID- 23153581
TI - Cbl and Itch binding sites in ERBB4 CYT-1 and CYT-2 mediate K48- and K63
polyubiquitination, respectively.
AB - ERBB receptors have an important function in mammalian development and normal
physiology, but overexpression and poor downregulation of ERBB receptors have
been associated with malignant growth. Ligand-induced ERBB receptor signaling is
terminated by clathrin-dependent receptor endocytosis, followed by incorporation
of activated receptor complexes into multi-vesicular bodies and subsequent
degradation in lysosomes. In the case of ERBB1, also known as the EGF receptor,
it has been shown that ubiquitination serves as a signal to facilitate
internalization and subsequent endosomal sorting, but little is known about the
role of ubiquitination of other ERBB receptors. In the present study we
investigated the regulation of ubiquitination and deubiquitination of the ERBB4
CYT-1 and CYT-2 isoforms in the context of chimeric EGFR-ERBB4 receptors. We
demonstrate that EGFR-ERBB4 CYT-2 chimera shows decreased ligand-induced
downregulation and EGF-degradation, as well as enhanced EGF recycling, when
compared to EGFR-ERBB4 CYT-1. Moreover we show that the mutation Y1103F in the
binding site for Cbl which is present in both CYT-1 and CYT-2, does not influence
ERBB4 endosomal trafficking. We further demonstrate that total ligand-induced
ubiquitination of CYT-1 is higher than that of CYT-2, whereby CYT-1
ubiquitination is mainly dependent on the PPXY(1056) Itch binding site for the E3
ligase Itch which is only present in CYT-1, while that of CYT-2 is dependent on
the Y1103 Cbl binding site. The E3-ligase c-Cbl is more efficiently
phosphorylated upon EGF stimulation of the CYT-2 than the CYT-1 isoform. Moreover
our data show that the pY1103 Cbl binding site is required for K48
polyubiquitination of both CYT-1 and CYT-2, whereas the PPXY(1056) Itch binding
site is required for K63-polyubiquitination of CYT-1. We further demonstrate that
EGF stimulation of EGFR-ERBB4 CYT-1 and CYT-2 does not result in efficient
binding to and tyrosine phosphorylation of the ESCRT-0 subunit Hrs. Finally, even
though CYT-1 shows ligand-induced K63-polyubiquitination, it is not subjected to
deubiquitination by the K63 polyubiquitin-specific AMSH deubiquitinating enzyme,
while CYT-1 is slightly deubiquitinated by USP8. We conclude that Cbl and Itch
binding sites in ERBB4 CYT-1 and CYT-2 mediate K48- and K63-polyubiquitination,
respectively.
PMID- 23153582
TI - Identification of a novel crosstalk between casein kinase 2alpha and NPM-ALK in
ALK-positive anaplastic large cell lymphoma.
AB - It was previously reported that beta-catenin contributes to the tumorigenesis of
ALK-positive anaplastic large cell lymphoma (ALK(+)ALCL), and the oncogenic
effects of beta-catenin in these tumors are promoted by NPM-ALK, an abnormal
fusion protein characteristic of ALK(+)ALCL. In this study, we hypothesized that
NPM-ALK promotes the oncogenic activity of beta-catenin via its functional
interactions with the Wnt canonical pathway (WCP). To test this hypothesis, we
examined if NPM-ALK modulates the gene expression of various members in the WCP.
Using a Wnt pathway-specific oligonucleotide array and Western blots, we found
that the expression of casein kinase 2alpha (CK2alpha) was substantially
downregulated in ALK(+)ALCL cells in response to siRNA knockdown of NPM-ALK.
CK2alpha is biologically important in ALK(+)ALCL, as its inhibition using 4,5,6,7
tetrabromobenzotriazole or siRNA resulted in a significant decrease in cell
growth and a substantial decrease in the beta-catenin protein level. Furthermore,
CK2alpha co-immunoprecipitated with NPM-ALK and regulated its level of serine
phosphorylation, a feature previously shown to correlate with the oncogenic
potential of this fusion protein. To conclude, this study has revealed a novel
crosstalk between NPM-ALK and CK2alpha, and our data supports the model that
these two molecules work synergistically to promote the tumorigenicity of these
lymphomas.
PMID- 23153583
TI - Molecular mechanisms coordinating functional and morphological plasticity at the
synapse: role of GluA2/N-cadherin interaction-mediated actin signaling in mGluR
dependent LTD.
AB - Long-lasting synaptic plasticity involves changes in both synaptic morphology and
electrical signaling (here referred to as structural and functional plasticity).
Recent studies have revealed a myriad of molecules and signaling processes that
are critical for each of these two forms of plasticity, but whether and how they
are mechanistically linked to achieve coordinated changes remain controversial.
It is well accepted that functional plasticity at the excitatory synapse is
dependent upon the activities of glutamate receptors. While the activation of
NMDARs (N-methyl-D-aspartic acid receptors) and/or mGluRs (metabotropic glutamate
receptors) is required for the induction of many forms of plasticity, AMPARs
(alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors), the
principal mediators of fast excitatory synaptic transmission, are the ultimate
targets of modifications that express functional plasticity. Investigations
exploring structural plasticity have been mainly focused on the small membranous
protrusions on the dendrites called spines. The morphological regulation of these
spines is mediated by the reorganization of the actin cytoskeleton, the
predominant structural component of the synapse. In this regard, the Rho family
of GTPases, particularly Rac1, RhoA and Cdc42, is found to be the central
regulator of spine actin and structural plasticity of the synapse. It is thought
that the collaborative interaction between functional and structural factors
underlies the sustained or permanent nature of long-lasting synaptic plasticity
such as long-term potentiation (LTP) and long-term depression (LTD), the most
extensively studied forms of synaptic plasticity widely regarded as cellular
mechanisms for learning and memory. However, data specifically pertaining to
whether and how these two distinct components are linked at the molecular level
remain sparse. In this regard, we have identified a number of synaptic proteins
that are involved in both structural and functional changes during mGluR
dependent LTD (mGluR-LTD). Among these are the GluA2 (formerly called GluR2)
subunit of AMPARs, Rac1 and Rac1-activated kinases. We have discovered that these
proteins interact and reciprocally regulate each other, which led us to
hypothesize that the GluA2-Rac1 interaction may serve as a coordinator between
functional and morphological plasticity. In this review, we will briefly discuss
the available evidence to support such a hypothesis.
PMID- 23153584
TI - LINE-1 ORF-1p functions as a novel androgen receptor co-activator and promotes
the growth of human prostatic carcinoma cells.
AB - Widespread interest in the mechanism of transcriptional regulation by the
androgen receptor (AR) has been stimulated by the finding that AR signaling is
critically important in the progression of human prostate cancers. Co-factors,
the co-repressors, or the co-activators are responsible for the regulation of AR
activation. The pro-oncogene human Long Interspersed Nucleotide acid Element-1
(LINE-1) encodes LINE-1 ORF-1p and plays important roles in the development and
progression of several human carcinomas. In this study, the results showed that
LINE-1 ORF-1p increased the AR transcriptional activity and in turn enhanced the
expression of prostate specific antigen (PSA) in the presence of R1881. A
physical protein-protein interaction between the AR signaling and the LINE-1 ORF
1p was identified by the immunoprecipitation assays and GST pull-down assays.
Furthermore, LINE-1 ORF-1p would function as a novel AR positive co-regulator
through modulating its cytoplasm/nucleus translocation and the recruitment to the
androgen response element in the PSA gene promoter. Our date also showed that the
LINE-1 ORF-1p promoted the proliferation and anchor-independent growth of LNCaP
(ligand dependent) and PC-3 (ligand independent) human prostatic carcinoma cells.
By investigating a novel role of the LINE-1 ORF-1p in the androgen/androgen
receptor signaling pathway regulation, our study identifies that LINE-1 ORF-1p
may be a novel AR co-regulator and molecular target for human prostate carcinoma
therapy.
PMID- 23153585
TI - Signaling mechanisms and functional roles of cofilin phosphorylation and
dephosphorylation.
AB - Cofilin and actin-depolymerizing factor (ADF) are actin-binding proteins that
play an essential role in regulating actin filament dynamics and reorganization
by stimulating the severance and depolymerization of actin filaments. Cofilin/ADF
are inactivated by phosphorylation at the serine residue at position 3 by LIM
kinases (LIMKs) and testicular protein kinases (TESKs) and are reactivated by
dephosphorylation by the slingshot (SSH) family of protein phosphatases and
chronophin. This review describes recent advances in our understanding of the
signaling mechanisms regulating LIMKs and SSHs and the functional roles of
cofilin phospho-regulation in cell migration, tumor invasion, mitosis, neuronal
development, and synaptic plasticity. Accumulating evidence demonstrates that the
phospho-regulation of cofilin/ADF is a key convergence point of cell signaling
networks that link extracellular stimuli to actin cytoskeletal dynamics and that
spatiotemporal control of cofilin/ADF activity by LIMKs and SSHs plays a crucial
role in a diverse array of cellular and physiological processes. Perturbations in
the normal control of cofilin/ADF activity underlie many pathological conditions,
including cancer metastasis and neurological and cardiovascular disorders.
PMID- 23153586
TI - Regulation of G protein signaling by the 70kDa heat shock protein.
AB - G protein-coupled receptors (GPCRs) transduce extracellular signals to the
interior of the cell by activating membrane-bound guanine nucleotide-binding
regulatory proteins (G proteins). An increasing number of proteins have been
reported to bind to and regulate GPCRs. We report a novel regulation of the
alpha(2A) adrenergic receptor (alpha(2A)-R) by the ubiquitous stress-inducible
70kDa heat shock protein, hsp70. Hsp70, but not hsp90, attenuated G protein
dependent high affinity agonist binding to the alpha(2A)-R in Sf9 membranes.
Antagonist binding was unchanged, suggesting that hsp70 uncouples G proteins from
the receptor. As hsp70 did not bind G proteins but complexed with the alpha(2A)-R
in intact cells, a direct interaction with the receptor seems likely. In the
presence of hsp70, alpha(2A)-R-catalyzed [(35)S]GTPgammaS binding was reduced by
approximately 70%. In contrast, approximately 50-fold higher concentrations of
hsp70 were required to reduce agonist binding to the stress-inducible 5
hydroxytryptamine(1A) receptor (5-HT(1A)-R). In heat-stressed CHO cells, the
alpha(2A)-R was significantly uncoupled from G proteins, coincident with an
increased localization of hsp70 at the membrane. The contrasting effect of hsp70
on the alpha(2A)-R compared to the 5-HT(1A)-R suggests that during stress,
upregulation of hsp70 may attenuate signaling from specific GPCRs as part of the
stress response to foster survival.
PMID- 23153587
TI - False lumen stent placement during iatrogenic coronary dissection.
AB - A 38-year-old woman without significant cardiovascular risk factors was admitted
in the coronary care unit with the diagnosis of acute coronary syndrome without
ST-segment elevation. In coronary angiography, left coronary artery system was
normal in the first contrast injection, but acute occlusion of the left main
coronary trunk (LCT) due to iatrogenic dissection was observed in the following.
The patient presented marked ST elevation, severe hypotension, hemodynamic
collapse, and loss of consciousness. Cardiopulmonary resuscitation (CPR) was
initiated, and two drug-eluting stents were consecutively placed in the LCT and
the left anterior descending coronary (LAD), but the patient died after 60 min of
continuous CPR. The autopsy showed dissection of the LCT and LAD coronaries with
both stents placed in the false lumen and hyperacute myocardial infarction in the
anterior left ventricular free wall. This case underlines the importance of
careful indication of invasive procedures and of taking in consideration their
potential risks.
PMID- 23153588
TI - Cyclosporine A and PSC833 inhibit ABCA1 function via direct binding.
AB - ATP-binding cassette protein A1 (ABCA1) plays a key role in generating high
density lipoprotein (HDL). However, the detailed mechanism of HDL formation
remains unclear; in order to reveal it, chemicals that specifically block each
step of HDL formation would be useful. Cyclosporine A inhibits ABCA1-mediated
cholesterol efflux, but it is not clear whether this is mediated via inhibition
of calcineurin. We analyzed the effects of cyclosporine A and related compounds
on ABCA1 function in BHK/ABCA1 cells. Cyclosporine A, FK506, and pimecrolimus
inhibited ABCA1-mediated cholesterol efflux in a concentration-dependent manner,
with IC(50) of 7.6, 13.6, and 7.0MUM, respectively. An mTOR inhibitor, rapamycin
also inhibited ABCA1, with IC(50) of 18.8MUM. The primary targets for these drugs
were inhibited at much lower concentrations in BHK/ABCA1 cells, suggesting that
they were not involved. Binding of [(3)H] cyclosporine A to purified ABCA1 could
be clearly detected. Furthermore, a non-immunosuppressive cyclosporine, PSC833,
inhibited ABCA1-mediated cholesterol efflux with IC(50) of 1.9MUM, and
efficiently competed with [(3)H] cyclosporine A binding to ABCA1. These results
indicate that cyclosporine A and PSC833 inhibit ABCA1 via direct binding, and
that the ABCA1 inhibitor PSC833 is an excellent candidate for further
investigations of the detailed mechanisms underlying formation of HDL.
PMID- 23153589
TI - Housing of growing rabbits in individual, bicellular and collective cages: fear
level and behavioural patterns.
AB - During growth (27 to 75 days of age), a total of 384 rabbits were kept in 72
individual cages, 48 bicellular cages (2 rabbits/cage) and 24 collective cages (9
rabbits/cage). To evaluate the effects of the housing system on the fear level
and behavioural patterns of rabbits at the two ages (39 to 45 days and 66 to 73
days), a tonic immobility test and an open-field test were conducted and their
behaviour was video recorded. In the tonic immobility test, the number of
attempts to induce immobility (1.38) was lower, and the duration of immobility
(47.8 s) was higher (0.05 < P < 0.01) in the rabbits housed in individual cages
than in those kept in bicellular (1.72 attempts and 25.0 s of immobility) and
collective cages (1.99 attempts and 25.0 s of immobility). During the open-field
test, the rabbits from individual and bicellular cages showed higher latency
(38.8 and 40.3 v. 27.0 s), a lower number of total (73.3 and 81.7 v. 91.9) and
central displacements (3.6 and 2.8 v. 5.4) and a shorter running time (11.8 and
13.6 s v. 17.7 s) and the time biting the pen (5.5 and 9.1 s v. 28.2 s) compared
with the rabbits kept in collective cages (0.05 < P < 0.001). During the 24-h
video recording, the rabbits in individual and bicellular cages spent less time
allogrooming (0.34% and 0.19% v. 1.44%), moving (0.74% and 0.60% v. 1.32%) and
running (0.08% and 0.03% v. 0.21%) than the rabbits in the collective cages (0.01
< P < 0.001). The lowest numbers of alerts and hops were observed in the rabbits
kept in bicellular cages. With increasing age, a lower number of rabbits were
sensitive to the immobility test and more rabbits entered the pen spontaneously
during the open-field test (P < 0.001). In conclusion, the rabbits in individual
cages exhibited the highest fear level and incomplete behavioural patterns; the
rabbits housed in collective cages showed the lowest fear levels and had the
possibility of expressing a wider range of behaviour; and the rabbits in
bicellular cages exhibited an inconsistent pattern of fear in the tonic
immobility and open-field tests. Probably, these rabbits were in a less stressful
condition compared with animals in individual cages because social contacts were
allowed, even if freedom of movement was more limited.
PMID- 23153590
TI - Analysis of disease recurrence and survival for women with uterine malignancies
undergoing robotic surgery.
AB - OBJECTIVES: To evaluate recurrence-free survival (RFS) and overall survival (OS)
for patients who underwent robotic-assisted laparoscopic hysterectomy (RALH) for
uterine malignancies. METHODS: Medical records from 372 patients with uterine
malignancies who underwent RALH from 3/06 to 3/09 at two institutions were
reviewed for clinico-pathologic data, adjuvant therapies, disease recurrence, and
survival. Median follow-up for survival analysis was 31 +/- 14 months. Thirty
(8.1%) patients were lost to follow-up before 12 months and censored from the
recurrence analysis. RESULTS: Mean age and BMI of 372 patients was 61.8 +/- 9.8
years and 32.2 +/- 8.4 kg/m(2) (range 19-70). Robotic procedures included RALH 16
(4.3%), RALH with pelvic lymphadenectomy (PL) 96 (25.8%), and RALH with pelvic
and-aortic lymphadenectomy (PAL) 252 (67.7%) cases. Histology included 319
(85.8%) endometrioid and 53 (12.6%) high-risk histologies. Mean pelvic and aortic
lymph node counts were 16.8 +/- 8.7 and 8.4 +/- 4.5, respectively. Lymph node
metastases were identified in 26 (7.3%) cases. Adjuvant therapies were prescribed
for 108 (29.1%) of patients: 7.8% brachytherapy, 1.9% pelvic
radiation+brachytherapy, 7.8% chemotherapy, 11.6% chemotherapy+radiation. Risk of
recurrence for all patients was 8.3% and 17 (4.6%) patients died of disease. The
estimated 3-year recurrence-free survival (RFS) for the entire study group was
89.3% and the estimated 5-year overall survival (OS) was 89.1%, compared to 92.5%
and 93.4% for the endometrioid sub-set. CONCLUSIONS: Patients with endometrial
cancer undergoing robotic hysterectomy with staging lymphadenectomies during our
3-years of robotic experience had low-risk for recurrence and excellent disease
specific survival at a median follow-up time of 31 months.
PMID- 23153591
TI - Old versus new FIGO staging systems in predicting overall survival in patients
with uterine leiomyosarcoma: a study of 86 cases.
AB - OBJECTIVES: Uterine leiomyosarcoma (uLMS) was staged using the FIGO system for
endometrial cancers. The new FIGO system takes into consideration tumor size
disregarding myometrial and cervical involvement. We aimed to compare the two
systems and see which more accurately predicts overall survival (OS). METHODS: 86
patients with uLMS (1984-2010) were retrospectively staged using both FIGO
systems. Mean OS rates were estimated using the Kaplan-Meier method. RESULTS:
More patients had stage-I disease by the new FIGO system (42 versus 33). Five
versus 18 and 27 versus 5 had old and new stage-II and III diseases respectively.
Five and 4 patients with old stage II and III uLMS respectively were downstaged
to stage I while 18 with old stage III were downstaged to stage II. Median follow
up was 23.5 months with a median OS of 114 (95% CI, 61-166) months. Although
patients with stage I tumors had a higher mean OS rate compared to those with
higher stage disease by either system, patients with old stage II-IV disease
showed similar mean OS rates, with stage III-IV patients having a slightly better
mean OS and a similar trend was observed with the new system. Patients with new
FIGO stage III had a higher mean OS rate than those with stage II or IV disease
(37.6 versus 28.1 and 34.3 months). Nonetheless, no statistical significant
differences were seen in OS according to stage using either system (p=0.786 and
p=0.400 respectively). CONCLUSION: Neither FIGO staging system is ideal in
classifying patients into four clinically significant stages.
PMID- 23153592
TI - [Fondaparinux as an alternative anticoagulant in heparin-induced thrombocytopenia
in the patient with a ventricular assist device].
AB - Heparin-induced thrombocytopenia is a reaction associated with the use of this
drug. It occurs in up to 3% of patients treated for at least 5 days. Its
treatment is to stop the heparin, and according to patient needs, replace it with
another anticoagulant. We present a patient who, after a heart transplant, and
the need for a ventricular assist device, required anticoagulation. The patient
developed heparin-induced thrombocytopenia. Heparin was stopped and
anticoagulation was replaced by fondaparinux. The peri-operative complications
and the management of the coagulation are described.
PMID- 23153593
TI - [Epidural and anesthesia for urgent cesarean section in a pregnant woman with
acute stroke].
PMID- 23153594
TI - [Bilateral and pneumomediastinal pneumothorax after transoral laser microsurgery
and tracheotomy].
AB - Transoral laser CO2 microsurgery is becoming an increasing used treatment option
for cancer of the larynx and the pharynx. Amongst the advantages it has compared
to open surgery and radiotherapy are, it less invasiveness, greater precision,
better functional preservation of the organ, and less procedure-associated
morbidity. However, this surgical technique is not without its complication, some
being rare up until now, but with great clinical importance. We present the case
of a patient subjected to microsurgery with a tracheotomy due to cancer of the
larynx, who suffered a subcutaneous emphysema, and a bilateral and
pneumomediastinal pneumothorax, requiring the appropriate measures for its
control and stabilisation, which are described. A review was also performed of
the current literature as regards anaesthetic considerations and the main peri
operative complications of laser microsurgery.
PMID- 23153595
TI - Plant-pathogen interactions: disease resistance in modern agriculture.
AB - The growing human population will require a significant increase in agricultural
production. This challenge is made more difficult by the fact that changes in the
climatic and environmental conditions under which crops are grown have resulted
in the appearance of new diseases, whereas genetic changes within the pathogen
have resulted in the loss of previously effective sources of resistance. To help
meet this challenge, advanced genetic and statistical methods of analysis have
been used to identify new resistance genes through global screens, and studies of
plant-pathogen interactions have been undertaken to uncover the mechanisms by
which disease resistance is achieved. The informed deployment of major, race
specific and partial, race-nonspecific resistance, either by conventional
breeding or transgenic approaches, will enable the production of crop varieties
with effective resistance without impacting on other agronomically important crop
traits. Here, we review these recent advances and progress towards the ultimate
goal of developing disease-resistant crops.
PMID- 23153596
TI - Our fragile intellect. Part I.
AB - New developments in genetics, anthropology, and neurobiology predict that a very
large number of genes underlie our intellectual and emotional abilities, making
these abilities genetically surprisingly fragile.
PMID- 23153597
TI - Our fragile intellect. Part II.
AB - Analysis of human mutation rates and the number of genes required for human
intellectual and emotional fitness indicates that we are almost certainly losing
these abilities. If so, how did we get them in the first place, and when did
things begin to change?
PMID- 23153598
TI - Patellar eversion does not adversely affect quadriceps recovery following total
knee arthroplasty.
AB - Although avoiding patellar eversion during a total knee arthroplasty (TKA) has
theoretical benefit in quadriceps recovery, there has been paucity of supportive
objective clinical results. We prospectively designed the study whether TKA
without patellar eversion has better quadriceps recovery in an objective,
dynamometer study. Seventy-two knees undergoing TKA with midvastus approach were
randomized into two groups according to patellar eversion or not. Clinical data
and objective quadriceps recovery using a dynamometer were investigated
preoperatively and postoperative at 6weeks, 3months, 6months and 1year. There
were no statistical differences between two groups throughout the follow-up
periods in recovery of quadriceps force or power and clinical data. Choosing to
evert patella during TKA using midvastus approach would not adversely affect
postoperative quadriceps recovery.
PMID- 23153599
TI - Diabetes mellitus and the incidence of deep vein thrombosis after total knee
arthroplasty: a retrospective study.
AB - We explored if there was an increased risk of DVT in patients with diabetes
mellitus undergoing total knee arthroplasty within 14days followup. We reviewed
245 patients undergoing total knee arthroplasty in our hospital between 2003 and
2011. The incidence of DVT within 14days after operations was compared between
diabetic patients and non-diabetic patients. There were 37 patients with DVT in
the diabetes group and 88 in the non-diabetes group within 14days followup
(p=0.002). The risk of DVT in patients with diabetes mellitus was 2.76 times the
risk in patients without diabetes mellitus using logistic regression modeling
(OR=2.76, p=0.003). Although it is still controversial, patients with diabetes
had a higher incidence rate of DVT after total knee arthroplasty in our study.
PMID- 23153600
TI - High diversity of Staphylococcus aureus and Staphylococcus pseudintermedius
lineages and toxigenic traits in healthy pet-owning household members.
Underestimating normal household contact?
AB - Forty-three unrelated pet-owning households were screened in Spain to study the
Staphylococcus aureus and Staphylococcus pseudintermedius nasal carriage, their
genetic lineages and virulence traits. Sixty-seven healthy owners and 66 healthy
pets were investigated. Isolates characterization was performed and potential
interspecies transmission was assessed. S. aureus was present in 51.2% of
households studied while S. pseudintermedius in 30.2%. Twenty-eight owners
(41.8%) carried S. aureus: one methicillin-resistant S. aureus (MRSA) [t5173-ST8
SCCmecIVa] and 27 methicillin-susceptible S. aureus (MSSA). Three owners (4.5%)
were colonized by methicillin-susceptible S. pseudintermedius (MSSP). Fifteen
pets (22.7%) carried S. pseudintermedius: two methicillin-resistant S.
pseudintermedius (MRSP) [ST71-SCCmecII/III; ST92-SCCmecV] and 13 MSSP; in
addition, 8 pets (12.1%) presented MSSA. High diversity of spa and sequence types
(STs) was detected. Typical livestock-associated S. aureus lineages (CC398, CC9)
were observed in humans and/or companion animals and hospital and/or community
acquired S. aureus lineages (CC45, CC121, CC5, CC8) were detected among pets.
Almost 40% of S. pseudintermedius were multidrug-resistant. S. aureus isolates
harboured a remarkable high number of virulence genes. The expA gene was detected
in 3 S. pseudintermedius isolates. Identical strains from both owners and their
pets were identified in 5 households (11.6%): (a) four MSSA (t073-ST45/CC45, t159
ST121/CC121, t209-ST109/CC9, t021-ST1654([new])/singleton) and (b) one multidrug
resistant MSSP (ST142([new])). Highly clonally diverse and toxigenic S. aureus
and S. pseudintermedius are common colonizers of healthy humans and pets. The
presence of these bacterial species, virulence genes, and interspecies
transmission detected, points out to consider pet ownership as a risk factor to
acquire, maintain and spread, potential pathogenic bacteria.
PMID- 23153601
TI - Twin Olympians: the hard science and the lives behind it.
PMID- 23153602
TI - Design, validity, and reliability of a pediatric resident JumpSTART disaster
triage scoring instrument.
AB - OBJECTIVE: To design an instrument for scoring residents learning pediatric
disaster triage (PDT), and to test the validity and reliability of the
instrument. METHODS: We designed a checklist-based scoring instrument including
PDT knowledge and skills and performance, as well as a global assessment.
Learners' performance in a 10-patient school bus crash simulation was video
recorded and scored with the instrument. Learners triaged the patients with a
color-coded algorithm (JumpSTART, Simple Triage and Rapid Treatment). Three
evaluators observed the recordings and scored triage performance for each
learner. Internal and construct validity of the instrument were established via
comparison of resident performance by postgraduate year (PGY) and correlating
instrument items with overall score. Validity was assessed with analysis of
variance and the D statistic. We calculated evaluators' intraclass correlation
coefficient (ICC) for each patient, skill, triage decision, and global
assessment. RESULTS: There were 37 learners and 111 observations. There was no
difference in total scores by PGY (P = .77), establishing internal validity.
Regarding construct validity, most instrument items had a D statistic of >0.5.
The overall ICC among scores was 0.83 (95% confidence interval [CI] 0.74-0.89).
Individual patient score reliability was high and was greatest among patients
with head injury (ICC 0.86; 95% CI 0.79-0.91). Reliability was low for an
ambulatory patient (ICC 0.29; 95% CI 0.07-0.48). Triage skills evaluation showed
excellent reliability, including airway management (ICC 0.91; 95% CI 0.86-0.94)
and triage speed (ICC 0.81; 95% CI 0.72-0.88). The global assessment had moderate
reliability for skills (ICC 0.63; 95% CI 0.47-0.75) and knowledge (ICC 0.64; 95%
CI 0.49-0.76). CONCLUSIONS: We report the validity and reliability testing of a
PDT-scoring instrument. Validity was confirmed with no performance differential
by PGY. Reliability of the scoring instrument for most patient-level triage,
knowledge, and specific skills was high.
PMID- 23153603
TI - New occupational and environmental causes of asthma and extrinsic allergic
alveolitis.
AB - Asthma and extrinsic allergic alveolitis (EAA) remain prevalent respiratory
diseases and the cause of a significant disease burden. This article reviews the
recent occupational and environmental causes described for these conditions. Even
over the limited time spam addressed by this article, novel agents and new data
relating to already suggested causes have been described. Various types of work
tasks or exposures are described that appear to cause both asthma and EAA.
Isocyanates, the best example of dual potential to cause asthma and EAA are
discussed, as is the new understanding of the role metal-working fluids play when
causing respiratory diseases.
PMID- 23153604
TI - Work-exacerbated asthma.
AB - A task force of the American Thoracic Society has defined work-exacerbated asthma
(WEA) as the worsening of asthma caused by conditions at work. Occupational
asthma (OA) is asthma that is initiated by occupational exposures in people
without prior asthma. In contrast, WEA is asthma (already present or coincident
[new onset]) that is worsened because of conditions at work. This difference is
critical because asthma is a common disease (present in approximately 7% of
working adults). Among working adults with asthma, approximately 20% may have
WEA. WEA has potential implications regarding asthma morbidity, health care use,
and the economy.
PMID- 23153605
TI - Occupational chronic obstructive pulmonary disease: an update.
AB - Chronic obstructive pulmonary disease represents a major cause of morbidity and
mortality in industrialized and nonindustrialized countries. Although tobacco use
remains the main factor associated with development of the disease, occupational
risk factors represent an important and preventable cause. The most common
occupationally related factors include exposure to organic dusts, metallic fumes,
and a variety of other mineral gases and/or vapors. This article summarizes the
literature on the subject and provides an update of the most recent advances in
the field.
PMID- 23153606
TI - Occupational rhinitis and other work-related upper respiratory tract conditions.
AB - The nose and upper airways form the initial area of impact for air pollutants and
allergens. The development of nasal allergies in the workplace (occupational
rhinitis) may herald subsequent development of occupational asthma. Exposure
controls, periodic surveillance, and early intervention may circumvent work
related airways disease and prevent unnecessary worker impairment and disability.
PMID- 23153607
TI - Indoor fuel exposure and the lung in both developing and developed countries: an
update.
AB - Almost 3 billion people worldwide burn solid fuels indoors. Despite the large
population at risk worldwide, the effect of exposure to indoor solid fuel smoke
has not been adequately studied. Indoor air pollution from solid fuel use is
strongly associated with chronic obstructive pulmonary disease, acute respiratory
tract infections, and lung cancer, and weakly associated with asthma,
tuberculosis, and interstitial lung disease. Tobacco use further potentiates the
development of respiratory disease among subjects exposed to solid fuel smoke.
There is a need to perform additional interventional studies in this field.
PMID- 23153608
TI - Newly recognized occupational and environmental causes of chronic terminal
airways and parenchymal lung disease.
AB - With the introduction of new materials and changes in manufacturing practices,
occupational health investigators continue to uncover associations between novel
exposures and chronic forms of diffuse parenchymal lung disease and terminal
airways disease. To discern exposure-disease relationships, clinicians must
maintain a high index of suspicion for the potential toxicity of occupational and
environmental exposures. This article details several newly recognized chronic
parenchymal and terminal airways. Diseases related to exposure to indium, nylon
flock, diacetyl used in the flavorings industry, nanoparticles, and the World
Trade Center disaster are reviewed. Also reviewed are methods in worker
surveillance and the potential use of biomarkers in the evaluation of exposure
disease relationships.
PMID- 23153610
TI - Military service and lung disease.
AB - Military personnel can be exposed to toxicants and conditions that can contribute
to lung diseases. This article describes what is known about these exposures and
diseases, focusing on the Iraq and Afghanistan wars. Adverse lung health outcomes
have been reported in US military personnel deployed to Iraq and/or Afghanistan.
Most studies to date have been hindered by limited deployment-specific exposure
assessment, lack of baseline lung health information, and variable medical
evaluations and case definitions. Further research is warranted. Medical
surveillance has been recommended for returning troops, but the challenges are
substantial.
PMID- 23153611
TI - Respiratory health in home and leisure pursuits.
AB - Many home-based and leisure activities can generate hazardous respirable
exposures. Routine domestic activities and a variety of hobbies, avocations, and
leisure pursuits have been associated with a spectrum of respiratory tract
disorders. Indoor environments present a special risk for high-intensity
exposures and adverse health effects. There are important knowledge gaps
regarding the prevalence of specific health hazards within and across
communities, exposure-response effects, population and individual
susceptibilities, best management strategies, the adverse health effects of mixed
exposures, and long-term clinical outcomes following exposures. The home
environment presents special health risks that should be part of the health
assessment.
PMID- 23153609
TI - Occupational and environmental causes of lung cancer.
AB - Because tobacco smoking is a potent carcinogen, secondary causes of lung cancer
are often diminished in perceived importance. The goal of this review is to
describe the occurrence and recent findings of the 27 agents currently listed by
the International Agency for Research on Cancer (IARC) as lung carcinogens. The
IARC's updated assessments of lung carcinogens provide a long-overdue resource
for consensus opinions on the carcinogenic potential of various agents.
Supplementary new information, with a focus on analytic epidemiologic studies
that has become available since IARC's most recent evaluation, are also
discussed.
PMID- 23153612
TI - Implications of OSA on Work and Work Disability Including Drivers.
AB - This article illustrates the impact of obstructive sleep apnea (OSA) on the work
force and emphasizes that there are public health risks and significant societal
financial losses in untreated OSA. Specifics of OSA impact on individuals are
discussed with regard to veterans, first responders, farmers, and pilots,
specially focusing on commercial vehicle drivers. The pathophysiology of OSA and
the consequence of impairment and disability due to OSA on work capacity are
introduced. Federal guidelines for occupational-specific recommendations are
presented. The health care provider's role in identifying and incorporating
effective screening and treatment strategies for workers with sleep apnea is
emphasized.
PMID- 23153613
TI - The classic pneumoconioses: new epidemiological and laboratory observations.
AB - The purpose of this article is to provide an update on selected issues of current
interest and recent developments related to 3 types of inorganic mineral dust
exposures causing classic forms of pneumoconiosis: coal mine dust, crystalline
silica, and asbestos. Common themes include new imaging modalities, emerging
exposures, and evolving appreciation of additional adverse health effects
associated with exposure to these inorganic mineral dusts.
PMID- 23153614
TI - Respiratory health effects of ambient air pollution: an update.
AB - There is new evidence for ambient air pollution (AAP) leading to an increased
incidence of respiratory diseases in adults. Research has demonstrated that co
exposures have the potential to dramatically augment the effects of AAP and lower
the threshold of effect of a given pollutant. Interactions between genes related
to oxidative stress and AAP seem to significantly alter the effect of AAP on an
individual and population basis. A better definition of vulnerable populations
may bolster local or regional efforts to remediate AAP. Advances in genetic
research tools have the potential to identify candidate genes that can guide
further research.
PMID- 23153615
TI - Induced sputum, exhaled nitric oxide, and particles in exhaled air in assessing
airways inflammation in occupational exposures.
AB - Sensitive methods to detect airways inflammation caused by exposures associated
with adverse respiratory effects are crucial, as is the identification of
individuals with early-stage disease. In this review, the use of induced sputum
and sampling of the fraction of nitric oxide to identify airways inflammation
associated with occupational exposures is discussed. In addition, a new method to
assess airways inflammation in small airways (sampling and analyses of particles
in exhaled air) is introduced.
PMID- 23153616
TI - Respiratory protection.
AB - Respiratory protection is used as a method of protecting individuals from
inhaling harmful airborne contaminants and in some cases to supply them with
breathable air in oxygen-deficient environments. This article focuses on the use
and types of personal respiratory protection (respirators) worn by individuals at
workplaces where airborne hazardous contaminants may exist. Respirators are
increasingly also being used in nonindustrial settings such as health care
facilities, as concerns regarding infectious epidemics and terrorist threats
grow. Pulmonologists and other clinicians should understand fundamental issues
regarding respiratory protection against airborne contaminants and the use of
respirators.
PMID- 23153617
TI - Lung diseases associated with occupational and environmental exposures subsume a
wide spectrum of conditions.
PMID- 23153618
TI - Development of solid lipid nanoparticles (SLNs) of lopinavir using hot self nano
emulsification (SNE) technique.
AB - Solid lipid nanoparticles (SLNs) of poor orally bioavailable drug lopinavir were
prepared using hot self nano-emulsification (SNE) technique. Hot isotropic
mixture of stearic acid, poloxamer and polyethylene glycol was spontaneously self
nano-emulsify in hot water and SLNs were formed with subsequent rapid cooling.
Self nano-emulsification ability of stearic acid, poloxamer and polyethylene
glycol mixture was assessed by ternary phase diagram study. Optimized SLNs were
having particle size of 180.6 +/- 2.32 nm (PDI=0.133 +/- 0.001), 91.5 +/- 1.3%
entrapment efficiency and zeta potential of -13.4 +/- 0.56 mV. SLNs were
evaluated by transmission electron microscopy (TEM) and atomic force microscopy
(AFM) for morphological study. Further, Differential scanning calorimetry (DSC)
and X-ray diffraction (XRD) of SLNs were also performed for checking solid state
characterization. Higher oral bioavailability was found for lopinavir loaded SLNs
in comparison to bulk lopinavir due to higher lymphatic drug transport (p<0.05).
Results indicate that SLNs of higher fatty acids can be successfully prepared by
hot SNE technique.
PMID- 23153619
TI - The estimation of patient-specific cardiac diastolic functions from clinical
measurements.
AB - An unresolved issue in patients with diastolic dysfunction is that the estimation
of myocardial stiffness cannot be decoupled from diastolic residual active
tension (AT) because of the impaired ventricular relaxation during diastole. To
address this problem, this paper presents a method for estimating diastolic
mechanical parameters of the left ventricle (LV) from cine and tagged MRI
measurements and LV cavity pressure recordings, separating the passive myocardial
constitutive properties and diastolic residual AT. Dynamic C1-continuous meshes
are automatically built from the anatomy and deformation captured from dynamic
MRI sequences. Diastolic deformation is simulated using a mechanical model that
combines passive and active material properties. The problem of non-uniqueness of
constitutive parameter estimation using the well known Guccione law is
characterized by reformulation of this law. Using this reformulated form, and by
constraining the constitutive parameters to be constant across time points during
diastole, we separate the effects of passive constitutive properties and the
residual AT during diastolic relaxation. Finally, the method is applied to two
clinical cases and one control, demonstrating that increased residual AT during
diastole provides a potential novel index for delineating healthy and
pathological cases.
PMID- 23153621
TI - Targeting specific traditional risk factors to improve cardiovascular outcomes:
Sound or flawed?
PMID- 23153620
TI - Leukotriene A4 hydrolase haplotype, diet and atherosclerosis: a twin study.
AB - OBJECTIVE: Atherosclerosis is an inflammatory process resulting from the
interaction between genetic and environmental factors. Leukotrienes are
inflammatory mediators generated from arachidonic acid, and genetic polymorphisms
involved in leukotriene metabolism are implicated in atherosclerosis. The
objectives of this study are to examine whether genetic variants in key
leukotriene enzymes are associated with atherosclerosis, and whether dietary
intake of competing leukotriene substrates modifies the effect of leukotriene
variants on atherosclerosis. METHODS: Atherosclerosis was assessed by common
carotid intima-media thickness (IMT) using ultrasound. Sequence variants within
arachidonate 5-lipoxygenase activating protein (ALOX5AP) and leukotriene A4
hydrolase (LTA4H) genes were analyzed with 32 single nucleotide polymorphisms
(SNPs) in 169 Caucasian twin pairs from the Vietnam Era Twin Registry. The
associations between genetic polymorphisms and carotid atherosclerosis, and gene
* diet interactions were examined by generalized estimating equation controlling
for potential confounders. RESULTS: A six-SNP haplotype in LTA4H, designated
HapE, was significantly associated with carotid IMT after adjusting for known
coronary risk factors. Twins carrying HapE had a much lower IMT compared to twins
not carrying (695 MUm vs. 750 MUm, p = 0.0007). Moreover, dietary intake of
polyunsaturated fatty acids strongly augmented the cardioprotective effect of
HapE among those with this haplotype but not those without, suggesting a
haplotype * diet interaction (interaction P(HapE*n-3) = 0.03, P(HapE*n-6) =
0.015). CONCLUSION: We identified a novel leukotriene haplotype that appears to
be protective toward subclinical atherosclerosis. This association is modified by
dietary intake of polyunsaturated fatty acids.
PMID- 23153622
TI - Association of coronary artery calcification and serum gamma-glutamyl transferase
in Korean.
AB - BACKGROUND AND OBJECTIVE: Elevated serum gamma-glutamyl transferase (GGT) has
been known to be associated with the cardiovascular disease. However, there is a
lack of researches on direct examination of relevance between serum GGT and
coronary artery calcification (CAC). Accordingly, the aim of this study was to
investigate the association between serum GGT levels and the prevalence of CAC in
Korean. METHODS: The study population consisted of 14,439 male and female adults
without coronary artery disease, who were conducted health examination from
January 2010 to December 2010. The prevalence of CAC in relation to the quartile
groups of serum GGT levels and odds ratio and 95% CI of CAC were analyzed using
multiple logistic regression model. RESULTS: The prevalence of CAC increased with
increasing GGT quartile (4.6%, 8.7%, 11.8% and 14.7% in the lowest, second,
third, highest GGT quartiles, respectively; p < 0.001). In the logistic
regression analysis adjusted for multiple variables, odds ratio (95% CI) for the
prevalence of CAC comparing the 1st GGT quartile to the 4th quartile were 2.43
(1.94-3.05) for all subjects, 1.49 (1.21-1.85) for men and 1.33 (0.62-2.87) for
women. CONCLUSION: Elevated serum GGT levels were independently associated with
the prevalence of CAC. Physicians and health care providers should be observant
regarding future development of coronary artery disease among people with
increasing concentration of serum GGT.
PMID- 23153623
TI - Influence of omega-3 polyunsaturated fatty acid-supplementation on platelet
aggregation in humans: a meta-analysis of randomized controlled trials.
AB - OBJECTIVE: Increased platelet activity predicts adverse cardiovascular events.
The objective was to assess the effects of long-chain omega-3 polyunsaturated
fatty acid (n-3 PUFA)-supplementation on platelet aggregation. METHODS AND
RESULTS: We conducted a meta-analysis of randomized controlled trials identified
using PubMed, Embase and the Cochrane Library. Fifteen studies were included. In
comparison to placebo using the random-effect model, n-3 PUFA-supplementation
significantly reduced adenosine diphosphate-induced platelet aggregation
(standard mean difference [SMD] = -1.23 with 95% confidence interval [CI] -2.24
to -0.23, p = 0.02) and platelet aggregation units, determined using the
VerifyNow((r)) rapid platelet-function assay system (SMD = -6.78 with 95% CI
12.58 to -0.98, p = 0.02). There was a trend toward decreased collagen-induced
(SMD = -0.70 with 95% CI -0.72 to 0.33, p = 0.18) and arachidonic acid-induced
platelet aggregation (SMD = -0.43 with 95% CI -2.26 to 1.40, p = 0.64) compared
with controls; however, statistical significance was not reached. CONCLUSIONS:
Our meta-analysis demonstrates that n-3 PUFA-supplementation is associated with a
significant reduction in platelet aggregation when the participants were at poor
health status, but not in healthy persons. High-risk patients with cardiovascular
disease and even diabetics may potentially benefit from n-3 PUFAs therapy.
However, n-3 PUFAs may not be effective in primary prevention. Larger trials need
to be carried out to confirm the present findings.
PMID- 23153624
TI - Semen preservation and artificial insemination in domesticated South American
camelids.
AB - Semen preservation and artificial insemination in South American camelids are
reviewed giving emphasis to work done in Peru and by the authors. Reports on
semen evaluation and the preservation process indicate that semen of alpacas and
llamas can be manipulated by making it liquid first. Collagenase appears to be
the best enzyme to eliminate viscosity. Tris buffer solution maintains a higher
motility than egg-yolk citrate, phosphate buffered saline (PBS), Triladyl, and
Merck-I extenders. Cooling of semen took 1h after collected, and equilibrated
with 7% glycerol presented a better motility and spermatozoa survival at 1, 7, 15
and 30days after being slowly frozen in 0.25mL plastic straws. Trials of
artificial insemination with freshly diluted semen and frozen-thawed semen are
encouraging and needs to be tested extensively under field conditions. Recently,
fertility rates varied from 3 to 67%. Semen preservation and most important,
artificial insemination appear to be a reality, and could be used to improve the
genetic quality of alpacas and llamas.
PMID- 23153625
TI - Artificial insemination in dromedary camels.
AB - Artificial insemination (AI) is an important technique in all domestic species to
ensure rapid genetic progress. The use of AI has been reported in camelids
although insemination trials are rare. This could be because of the difficulties
involved in collecting as well as handling the semen due to the gelatinous nature
of the seminal plasma. In addition, as all camelids are induced ovulators, the
females need to be induced to ovulate before being inseminated. This paper
discusses the different methods for collection of camel semen and describes how
the semen concentration and morphology are analyzed. It also examines the use of
different buffers for liquid storage of fresh and chilled semen, the ideal number
of live sperm to inseminate and whether pregnancy rates are improved if the
animal is inseminated at the tip of the uterine horn verses in the uterine body.
Various methods to induce ovulation in the female camels are also described as
well as the timing of insemination in relation to ovulation. Results show that
collection of semen is best achieved using an artificial vagina, and the highest
pregnancy rates are obtained if a minimum of 150*10(6) live spermatozoa (diluted
in Green Buffer, lactose (11%), or I.N.R.A. 96) are inseminated into the body of
the uterus 24h after the GnRH injection, given to the female camel to induce
ovulation. Deep freezing of camel semen is proving to be a great challenge but
the use of various freezing protocols, different diluents and different packaging
methods (straws verses pellets) will be discussed. Preliminary results indicate
that Green and Clear Buffer for Camel Semen is the best diluent to use for
freezing dromedary semen and that freezing in pellets rather than straws result
in higher post-thaw motility. Preservation of semen by deep-freezing is very
important in camelids as it prevents the need to transport animals between farms
and it extends the reproductive life span of the male, therefore further work
needs to be carried out to improve the fertility of frozen/thawed camel
spermatozoa.
PMID- 23153626
TI - Development of a large commercial camel embryo transfer program: 20 years of
scientific research.
AB - Embryo transfer in camels was initiated to respond to demand from the camel
industry particularly in the United Arab Emirates since 1990. This paper reviews
the research performed in critical areas of reproductive physiology and
reproductive function evaluation that constitute a pre-requisite for a successful
embryo transfer program. A description of donor and recipient management as well
as a retrospective evaluation of calf production in the embryo transfer program
at Sweihan, UAE is provided. The program utilized two management systems for
donors, with and without ovarian superstimulation. Non-stimulated donors are
flushed every 14-15 days with a mean embryo production per year per female of
8.5+/-3.1 (mean+/-SEM). Response to gonadotropin stimulation is extremely
variable. FSH doses and frequency of administration is often adjusted to a
specific female. In the period of 1990-2010, 11,477 embryos were transferred to
recipients. Transfers from 1990 to 2009 (n=10,600) resulted in 2858 weaned
calves, representing an overall efficiency (% weaned calves/transfer) of 27%.
Pregnancy rates at 60 days post transfer varied from 19 to 44%. Pregnancy length
following transfer is extremely variable. A major challenge in a large embryo
transfer program is finding good quality recipients. Causes of pregnancy and
neonatal losses are under study.
PMID- 23153627
TI - Survey of accidental dural puncture rates by anaesthetic trainees using constant
or intermittent plunger pressure.
PMID- 23153629
TI - Effect of different pre-irradiation times on curcumin-mediated photodynamic
therapy against planktonic cultures and biofilms of Candida spp.
AB - OBJECTIVES: The aim of this study was to evaluate the effects of pre-irradiation
time (PIT) on curcumin (Cur)-mediated photodynamic therapy (PDT) against
planktonic and biofilm cultures of reference strains of Candida albicans, Candida
glabrata and Candida dubliniensis. MATERIALS AND METHODS: Suspensions and
biofilms of Candida species were maintained in contact with different
concentrations of Cur for time intervals of 1, 5, 10 and 20min before irradiation
and LED (light emitting diode) activation. Additional samples were treated only
with Cur, without illumination, or only with light, without Cur. Control samples
received neither light nor Cur. After PDT, suspensions were plated on Sabouraud
Dextrose Agar, while biofilm results were obtained using the XTT-salt reduction
method. Confocal Laser Scanning Microscopy (CLSM) observations were performed to
supply a better understanding of Cur penetration through the biofilms after 5 and
20min of contact with the cultures. RESULTS: Different PITs showed no statistical
differences in Cur-mediated PDT of Candida spp. cell suspensions. There was
complete inactivation of the three Candida species with the association of
20.0MUM Cur after 5, 10 and 20min of PIT. Biofilm cultures showed significant
reduction in cell viability after PDT. In general, the three Candida species
evaluated in this study suffered higher reductions in cell viability with the
association of 40.0MUM Cur and 20min of PIT. Additionally, CLSM observations
showed different intensities of fluorescence emissions after 5 and 20min of
incubation. CONCLUSION: Photoinactivation of planktonic cultures was not PIT
dependent. PIT-dependence of the biofilm cultures differed among the species
evaluated. Also, CLSM observations confirmed the need of higher time intervals
for the Cur to penetrate biofilm structures.
PMID- 23153628
TI - Adipocytokine signaling is altered in Flinders sensitive line rats, and
adiponectin correlates in humans with some symptoms of depression.
AB - Major depression is a complex multi-factorial disorder with a lifetime diagnosis
of nearly 1 out of 6. We used the Flinders Sensitive Line (FSL) of rats, a model
of depression, and the parent Sprague-Dawley (SD) rats to identify genes, gene
ontology categories and pathways associated with depression. Depression-like
behavior was verified in the FSL line by forced swim testing, with FSL animals
exhibiting greater immobility compared to SD rats. RNA samples from the
hippocampus were isolated from a group of experimentally naive FSL and SD rats
for microarray analysis. Microarray analysis yielded a total of 361 genes that
were differentially regulated between FSL and SD rats, with catechol-O
methyltransferase (COMT) being the most up-regulated. The genes that were
differentially regulated between FSL and SD rats were subjected to bioinformatic
analysis using the Database for Annotation, Visualization and Integrated
Discovery (DAVID), which yielded several gene ontology categories that were
overrepresented. Subsequent pathway analysis indicated dysregulation of the
adipocytokine signaling pathway. To test the translational impact of this
pathway, metabolic factors and psychiatric symptoms were evaluated in a sample of
human research participants. Results from our human subjects indicated that
anxiety and a subset of depressive symptoms were correlated with adiponectin
levels (but not leptin levels). Our results and those of others suggest that
disruption of the adipocytokine signaling pathway may be a critical component of
the depressive-like behaviors observed in the FSL rats and may also be an
important indicator of depressive and anxiety symptoms in humans.
PMID- 23153630
TI - Unusual case of oral chronic lymphocytic leukemia presenting as recurrent
epistaxis and asymptomatic intraoral swelling.
AB - INTRODUCTION: Usually, oral manifestations of chronic lymphocytic leukemia CLL
are related to an advanced stage of a diagnosed disease, and rarely may lead to
diagnosis. CLL can also present as bleeding, rarely isolated. We report a rare
case of CLL the first symptoms of which were recurrent epistaxis and asymptomatic
intraoral swelling. CASE PRESENTATION: A 74-year-old woman consulted for
recurrent epistaxis. She presented with a small asymptomatic swelling in the left
superior vestibule. Computed tomography revealed a tissular-like mass without
invasion of surrounding tissues. The hemogram revealed thrombocytopenia and
leukocytosis with 51% of lymphocytes. The immuno-histochemical analysis of the
lesion and of the bone marrow allowed diagnosing stage IV CLL. DISCUSSION: CLL
may present as unusual symptoms. It should be suspected in elderly patients
presenting with atypical clinical signs such as oral swelling or signs of bone
marrow involvement.
PMID- 23153631
TI - [Schmid-Meyer fronto-temporal flap for nasal reconstruction].
AB - INTRODUCTION: Many surgical techniques have already been described to repair full
thickness defects of the inferior part of the nose. The Schmid-Meyer fronto
temporal flap procedure, a little known technique, is based on the old principle
of autonomization of a cutaneous flap and uses a tailor-made composite
cartilaginous graft placed in the temporal region. This graft is progressively
detached and allows mucosal/cartilaginous/and cutaneous nasal repair. Can this
technique still be used for nasal full-thickness reconstruction? PATIENTS AND
METHOD: Nine cases of nasal reconstruction using this procedure were performed.
The 4-steps of the operative technique were described and the results were
analyzed retrospectively. RESULTS: This procedure allows, for some specific
indications, excellent reconstruction of the ala, the columella or the nasal tip.
In eight cases out of nine, the result was judged good or very good by both
patients and physicians. In 78%, the reconstruction was performed under local
anesthesia. DISCUSSION: The Schmid-Meyer flap procedure may still be used for
full-thickness reconstruction of the lower third of the nose because it allows a
high quality of nasal reconstruction and few scar sequels.
PMID- 23153632
TI - [Treatment of Poland syndrome thorax deformity with the lipomodeling technique:
about ten cases].
AB - The correct management, with the classic techniques, of the thoracic deformity in
Poland's syndrome is difficult, with often insatisfactory results. The current
surgical treatment involves the use of prothetic material and/or different flaps
with their own complications and scares. The experience of our team with fat
grafting (we named lipomodeling) in breast reconstruction helped us to propose
the correction of the thoracic and mammary deformity by repeated fat transfer
sessions. Fat grafting is commonly used in our team since 1998 in various
indication of breast surgery. We reviewed retrospectively our ten first cases of
thoracic deformity in Poland's syndrome treated with only fat grafting. Patients
had repeated procedures until obtaining a satisfactory result. The fat was
harvested from the thigh, buttocks, and abdomen. There were young patients with a
mean age of 16years old (from 12 to 24). The mean follow-up was 51months. An
average of 2.9 procedures (1 to 5) with 255cm(3) of fat injection at each
procedure was needed to obtain symetry. Hundred percent of the patients were
satisfied. No complication was noted. As reported, the reconstruction of the
thoracic deformity and the mammary shape can be obtained by fat grafting. The
absence of a flap donor site sequelae and the absence an implant allow this
technique to be simple, reproductible, and without great complication. These
criteria match well the surgical management of this deformity, which is mainly
aesthetic. Moreover, the secondary benefit of liposuction of disgracious
steatomery helps the acceptance of the procedure. Therefore in our hands, fat
grafting to the breast (lipomodeling) is now our first choice treatment in
thoracic Poland syndrome deformity. Given the rarity of this syndrome, we
recommend a treatment by an operator who makes the learning curve of
lipomodeling, and who often deals with Poland syndrome.
PMID- 23153633
TI - [Strategies in case of unusable internal mammary vessels in a mammary
reconstruction by DIEP].
AB - INTRODUCTION: We analyzed the strategy of microvascular connection during the
DIEP in case of unusable internal mammary vessels in intraoperative period.
MATERIAL AND METHOD: It is about five cases of mammary reconstructions by DIEP
practiced in a plastic surgery department. We modified our connections because
the quality of the artery and/or the vein was considered insufficient. RESULTS:
In case of internal mammary artery unusable, we changed the donor site and the
flap was anastomosed with circumflexe scapular vessels. In case of internal
mammary vein judged unusable but with usable artery, we anastomosed the DIEP with
the internal mammary artery and with the cephalic vein. We added a venous
substitution by the second connection with the deep inferior epigastric venous by
coupler's technique. CONCLUSION: Circumflexe scapular artery was the first
alternative of internal mammary artery. In every case we protected the
thoracodorsal pedicle.
PMID- 23153634
TI - [Treatment of facial paralysis with temporalis lengthening myoplasty and
dysarthria improvement].
AB - INTRODUCTION: The dysfunctions engendered by the peripheral facial paralysis
(PFP) induce modifications of the verbal and para-verbal functions. The purpose
of our study was to observe if the temporalis lengthening myoplasty (TLM) allowed
to decrease dysarthria observed on the operated patients. MATERIALS AND METHODS:
We followed-up seven patients affected by a peripheral facial paralysis with
various etiologies. Due to specifics needs of this study, we created an
evaluation grid of the articulation, which allowed us to measure evolutions after
the operation by a tri-phase evaluation: before surgery, at 3 and 6months after
it. RESULTS: Results show a definite improvement of dysarthria in the whole test
group. CONCLUSION: TLM operation, in addition to be very efficient for the
recovering of the paralyzed side, can also treat dysarthria on these patients.
PMID- 23153635
TI - Implementing a Virtual Exchange Project for student nurses in Queensland and
Nottingham.
AB - This paper discusses the design and initial progress made with a virtual learning
environment to help student nurses develop an understanding of cultural awareness
and globalization. Using a Web-based application the Virtual Exchange Project was
designed to facilitate study-elsewhere experiences located in the student's own
setting. Promotion of the United Nations' Millennium Development goals provided
an opportunity for student nurses to explore changes in global health and disease
patterns, nursing education and systems of nurse regulation in the United Kingdom
and Australia. A pedagogical framework created for this activity acknowledges the
social and academic identities that learners often use, when working together in
a virtual environment. The architecture of the Virtual Exchange supports local
conversations about nurse education and health and social issues across
hemispheres.
PMID- 23153636
TI - Study of the specific interaction between L-methionine chromatography support and
nucleotides.
AB - The interaction of L-methionine-agarose with 5'-mononucleotide was investigated
by saturation transfer difference (STD)-nuclear magnetic resonance (NMR)
spectroscopy. Chromatographic experiments were also performed using homo
oligonucleotides of distinct molecular masses (1-30 nucleotides) to explore the
effect of base hydrophobicity, temperature, pH and salt concentration on the
retention of homo-oligonucleotides to L-methionine-agarose support. With STD-NMR,
the results reveal that hydrophobic residues, such as the CH3 of thymine and
adenine, can preferentially recognise the L-methionine side chain of the support.
Also, 5'-TMP led to more contacts with the support, while 5'-UMP presented fewer
STD contacts. For 5'-UMP, 5'-CMP and 5'-GMP, the main interaction with the
support was through the sugar-phosphate backbone. Similar binding profiles were
obtained using chromatographic experiments. Indeed, 5'-TMP had the highest
retention time, followed by 5'-GMP, 3'-AMP, 5'-UMP and 5'-CMP. In general, the
retention factor of homo-oligonucleotides was higher for ammonium sulphate
concentration 1.5 M. For the polyT3-polyT30 series, the retention time increased
by about three-fold, indicating that larger homo-oligonucleotides have more
hydrophobic bases, thus enhancing contact with the L-methionine support. The
temperature (5, 20 and 35 degrees C) did not influence homo-oligonucleotide
retention. However, the retention time slightly increased when the pH was lower
than 9. The STD-NMR technique combined with chromatographic experiments was thus
successfully used to screen amino acid-nucleotide interactions.
PMID- 23153637
TI - Evaluation of a direct high-capacity target screening approach for urine drug
testing using liquid chromatography-time-of-flight mass spectrometry.
AB - In this study a rapid liquid chromatography-time-of-flight mass spectrometry
method was developed, validated and applied in order to evaluate the potential of
this technique for routine urine drug testing. Approximately 800 authentic
patient samples were analyzed for amphetamines (amphetamine and methamphetamine),
opiates (morphine, morphine-3-glucuronide, morphine-6-glucuronide, codeine and
codeine-6-glucuronide) and buprenorphines (buprenorphine and buprenorphine
glucuronide) using immunochemical screening assays and mass spectrometry
confirmation methods for comparison. The chromatographic application utilized a
rapid gradient with high flow and a reversed phase column with 1.8 MUm particles.
Total analysis time was 4 min. The mass spectrometer operated with an
electrospray interface in positive mode with a resolution power of >10,000 at m/z
956. The applied reporting limits were 100 ng/mL for amphetamines and opiates,
and 5 ng/mL for buprenorphines, with lower limits of quantification were 2.8-41
ng/mL. Calibration curves showed a linear response with coefficients of
correlation of 0.97-0.99. The intra- and interday imprecision in quantification
at the reporting limits were <10% for all analytes but for buprenorphines <20%.
Method validation data met performance criteria for a qualitative and
quantitative method. The liquid chromatography-time-of-flight mass spectrometry
method was found to be more selective than the immunochemical method by producing
lower rates of false positives (0% for amphetamines and opiates; 3.2% for
buprenorphines) and negatives (1.8% for amphetamines; 0.6% for opiates; 0% for
buprenorphines). The overall agreement between the two screening methods was
between 94.2 and 97.4%. Comparison of data with the confirmation (LC-MS) results
for all individual 9 analytes showed that most deviating results were produced in
samples with low levels of analytes. False negatives were mainly related to
failure of detected peak to meet mass accuracy criteria (+/-20 mDa). False
positives was related to presence of interfering peaks meeting mass accuracy and
retention time criteria and occurred mainly at low levels. It is concluded that
liquid chromatography-time-of-flight mass spectrometry has potential both as a
complement and as replacement of immunochemical screening assays.
PMID- 23153638
TI - Determination of cyclic guanosine- and cyclic adenosine monophosphate (cGMP and
cAMP) in human plasma and animal tissues by solid phase extraction on silica and
liquid chromatography-triple quadrupole mass spectrometry.
AB - 3',5'-Cyclic guanosine monophosphate (cGMP) and 3',5'-cyclic adenosine
monophosphate (cAMP) are essential second messenger molecules. They are involved
in signal transduction within cells, in physiological functions such as
neurotransmission and in the modulation of cell growth and differentiation of
organisms, respectively. A quantitative solid phase extraction method (SPE) based
on hydrophilic interaction on silica was developed and applied to both plasma and
tissue samples. The stable isotope-labeled internal standards 2D1, 15N3-3',5'
cGMP and 13C10, 15N5-3',5'-cAMP were added prior to the sample preparation to
ensure high precision and accuracy. The samples were analyzed by reversed-phase
liquid chromatography (RP-LC). Negative electrospray (ESI)-MS/MS was used to
selectively monitor several transitions of each metabolite. The method for the
analysis of 3',5'-cAMP and 3',5'-cGMP in plasma was validated in the range of
0.15-20 ng/mL (R2=0.9996 and 0.9994 for 3',5'-cAMP and 3',5'-cGMP, respectively).
Basal plasma concentrations for fifteen healthy human patients determined with
this method varied between 4.66-9.20 ng/mL for 3',5'-cAMP and between 0.30-1.20
ng/mL for 3',5'-cGMP, with precisions better than 9.1%. 3',5'-cGMP and 3',5'-cAMP
together with their 2',3'-isomers were also determined in a semi quantitative way
in animal tissues. The structures of the isomers were confirmed by analysis with
LC-high resolution time-of-flight MS and subsequently by comparison of retention
times with standards.
PMID- 23153639
TI - On-line capillary electrophoresis for enhanced detection sensitivity of feline
panleukopenia virus.
AB - A rapid on-line capillary electrophoresis (CE) method for highly sensitive
detection of DNA molecules with specific lengths was developed based on the
combination of base stacking (BS) and programmed field strength gradients (PFSG).
The BS method has been performed for on-column concentration to improve detection
sensitivity without any modification of the CE system. PFSG increased the
electrophoretic velocity of DNA molecules, which effectively decreased analysis
time. Using the BS and PFSG combination, the amplified PCR product (340-bp DNA)
of cats infected with feline panleukopenia virus was detected within 6.5min.
Detection sensitivity (~10-fold) was enhanced compared to conventional CE
analysis. The combined on-line CE/BS-PFSG methodology could be an effectively
rapid analysis technique for the highly sensitive detection of disease-related
specific DNA molecules.
PMID- 23153640
TI - Analysis of new potential anticonvulsant compounds in mice brain tissue by
SPE/HPLC/DAD.
AB - This paper describes a novel reversed-phase high performance liquid
chromatography (RP-HPLC) with photo-diode array detection (DAD) method for the
determination of three new derivatives of 4-alkyl-5-(3-chlorophenyl)-2,4-dihydro
3H-1,2,4-triazole-3-thione with different antiepileptic activity in the brains of
mice treated with the doses of 300mgkg(-1) of body weight. Samples were prepared
by solid-phase extraction (SPE) method using BAKERBONDTM spe Octadecyl (C(18))
and analyzed by the use of an isocratic elution mode over an Zorbax Extend-C18
column (150mm*4.6mm I.D., 5-MUm, Agilent Technologies). The mobile phase
consisted of 80% methanol (for compound TP-315) and 85% acetonitrile (for
compound TP-321) for 80% 2-propanol (for TP-323) at a flow rate of 1.0mLmin(-1)
and 0.5mLmin(-1) in the last case. Gradient elution mode was also proposed for
all examined analytes in mixture with common antiepileptic drugs: carbamazepine,
phenobarbital and phenytoin in view of possible synergistic activity. Photodiode
array investigations of the peaks after degradation studies indicate the
stability of the compounds under conditions proposed for sample preparation
procedure. Linear coefficients of correlation (r(2)) were >0.995 for all
analytes. The proposed strategy gives extraction yields higher than 95% with the
intra- and inter-day relative standard deviation lower than 3% and 5%,
respectively. This method was applied to the analysis of brain tissue of mice
treated with investigated compounds. Obtained results enable to explain the
differences in their pharmacological activity.
PMID- 23153641
TI - Comparison of methanol and acetonitrile eluents for the quantitation of chelators
specific to soft-metal ions by HPLC.
AB - HPLC eluent systems employing acetonitrile and methanol were evaluated for the
quantitation of glutathione (GSH) and phytochelatin (PC(n)), a family of peptides
implicated in heavy-metal detoxification in higher plants. The detection system
is based on the dequenching of copper(I)-bathocuproine disulfonate and is
specific for soft-metal chelators. Although both elution systems yielded
comparable analytical performance for each PC(n), the acetonitrile system had a
lower sensitivity for GSH and a steadily increasing baseline. The inferior
properties of the acetonitrile system may be due to complex formation between
acetonitrile and Cu(I) ions. Both methods were applied to measure peptide levels
in the primitive red alga Cyanidioschyzon merolae. Coefficients of variation
(CVs) were less than 5%, except for GSH and PC(4) determinations in the
acetonitrile system, in cases when CV values were found to be 8.8% and 6.3%,
respectively. Recoveries were greater than 96%, except for GSH determination in
the acetonitrile system, with a recovery of 84.4%; however, the concentration
measured in the acetonitrile system did not differ from that measured in the
methanol system at a significance level of 0.05.
PMID- 23153642
TI - Investigation of bioaccumulation profile of oestrogens in zebrafish liver by
hollow fibre protected liquid phase microextraction with gas chromatography-mass
spectrometric detection.
AB - The applicability of hollow fibre protected liquid phase microextraction (HF
LPME) for the determination of three oestrogens, namely estrone (E1), 17beta
estradiol (E2) and 17alpha-ethinylestradiol (EE2) from individual zebrafish liver
samples, in a bioaccumulation study on these organisms, is reported. The
oestrogens were extracted from single, mechanically crushed and minced livers
from fish that were heaved in tubes containing water spiked at low concentration
of the analytes. Extraction was performed with ~3 MUL of toluene contained in the
hollow fibre. In order to achieve high extraction efficiency, the parameters that
could affect the effectiveness of HF-LPME were optimized, i.e. the extracting
organic solvent, extraction time, stirring speed and pH of the aqueous phase. For
gas chromatography/mass spectrometry (GC/MS) analysis, injection port
derivatization of the oestrogens with bis(trimethylsilyl)trifluoroacetamide was
conducted. Under the most favourable extraction and derivatization conditions,
enrichment factors of 158-279 were obtained. Linearity of the HF-LPME-GC/MS
method was evaluated from 1 to 50 MUg/L and the coefficient of determination (r2)
ranged from 0.9687 to 0.9926. The LODs were between 0.017 and 0.033 MUg/L (at a
signal to noise ratio of 3) with relative standard deviations (RSDs, analytes
spiked at 5 MUg/L) of between 15 and 17% (n=3).
PMID- 23153643
TI - High-throughput bioanalytical method for analysis of synthetic cannabinoid
metabolites in urine using salting-out sample preparation and LC-MS/MS.
AB - Herbal smoking mixtures which are sold as incense or potpourri and often referred
to as 'Spice' are actually inactive plant matter adulterated with alkylamino
indole based synthetic cannabinoids such as JWH-018 and JWH-073. Due to the
inclusion of five synthetic cannabinoids, including JWH-018 and JWH-073, as
Schedule I drugs by the Drug Enforcement Agency (DEA) in March 2011, it has
become necessary for forensic laboratories to develop analytical methods to test
for the presence of metabolites of synthetic cannabinoids. When a new analyte of
interest emerges, most laboratories strive to develop a sample preparation
procedure and validate an analytical method as quickly as possible and therefore,
rely on effective but time consuming traditional protocols such as solid phase
and liquid-liquid extraction. This research focuses on the examination of all
aspects of sample preparation and analytical method development to streamline the
analysis of four urinary metabolites of JWH-018 and JWH-073. A detailed
evaluation of the beta-glucuronide hydrolysis step lead to the reduction of time
required for hydrolysis from 1h at 50 degrees C to only 10min at room
temperature. By utilizing a salting-out assisted liquid-liquid extraction (SALLE)
in place of traditional liquid-liquid extraction with a volatile solvent,
processing time was saved and waste was reduced. The analysis run time was also
shortened to one-third of a typical published run time by utilizing UPLC with
isocratic conditions in place of conventional HPLC running a gradient method.
PMID- 23153644
TI - Synthese and characterization of boronic acid functionalized macroporous uniform
poly(4-chloromethylstyrene-co-divinylbenzene) particles and its use in the
isolation of antioxidant compounds from plant extracts.
AB - Aminophenyl boronic acid (APBA) carrying uniform-macroporous
poly(chloromethylstyrene-co-divinylbenzene), poly(CMS-co-DVB) particles were
synthesized for selective separation of cis-diol-containing flavonoids from plant
extracts. For this purpose, 2.5 MUm polystyrene seed particles were first swelled
by a mixture of dibutyl phthalate (DBP), toluene and dodecanol, then by a monomer
mixture including CMS and DVB. The repolymerization of the monomer phase in the
swollen seed particles provided macroporous and uniform particles, approximately
7 MUm in size. Chlorine atoms on the surface of these particles were derivatized
with APBA to gain affinity properties for flavonoids containing vicinal hydroxyl
groups. Model adsorption studies showed that these particles selectively adsorbed
quercetin and rutin containing cis-diol groups, but did not adsorb apigenin
similar to quercetin and not carrying cis-diol groups. These particles were also
tested in adsorption/desorption studies for ethanol and ethyl acetate extracts of
the Hypericum perforatum (HP) stems to obtain high antioxidant mixtures. With
ethanol extract, the antioxidant activity of the desorption solution was a bit
higher than that of the post-adsorption solutions. However, the DPPH radical
scavenging activity of the desorption solution decreased with respect to the
original extract and post-adsorption solutions. A similar result was obtained for
the antioxidant activity of the desorption solution using ethyl acetate extract.
An interesting result was obtained that DPPH radical scavenging activity of the
post-adsorption solution was higher than that of the original ethyl acetate
extract and desorption solutions. These results were attributed to selective
adsorption of antioxidant characterized cis-diol-containing apolar molecules much
more rather than that radical scavenger characterized polar molecules.
PMID- 23153645
TI - Improving the imprinting effect by optimizing template:monomer:cross-linker
ratios in a molecularly imprinted polymer for sulfadimethoxine.
AB - Four non-covalently prepared molecularly imprinted polymers (MIPs) for
sulfadimethoxine (SDM) were prepared using different ratios of SDM template,
methacrylic acid monomer, and ethylene glycol dimethacrylate cross-linker. The
imprinting factor (IF) was calculated by comparing the retention of SDM on the
imprinted polymer with a comparable non-imprinted polymer. The
template:monomer:cross-linker ratio of 1:6:20 resulted in an IF of 3.94 which is
higher than found in previous studies. A significant decrease in IF to 0.89 when
template:cross-linker ratio was 1:40 contradicts most literature where higher
cross-linker concentration improves selectivity. IF was 4.36 when 20% water was
added to the acetonitrile HPLC mobile phase during evaluation. Retention of SDM
increased as water concentration changed as: 20, 40, 0, 60 and 70%, indicating a
combination of shape recognition, hydrogen bonding and hydrophobic interactions
contributing to retention of analyte. The MIP has the potential for use in SPE
for purification and concentration of SDM and with further optimization, possibly
direct HPLC analysis.
PMID- 23153646
TI - Determination of tamsulosin in human plasma by liquid chromatography/tandem mass
spectrometry and its application to a pharmacokinetic study.
AB - Tamsulosin, a selective alpha1-adrenoceptor antagonist, is used for the treatment
of benign prostatic hyperplasia (BPH). We developed and validated a rapid,
sensitive, and simplified liquid chromatography analytical method utilizing
tandem mass spectrometry (LC-MS/MS) for the determination of tamsulosin in human
plasma. After liquid-liquid extraction with methyl t-butyl ether, chromatographic
separation of tamsulosin was achieved using a reversed-phase Luna C18 column (2.0
mm * 50 mm, 5 MUm particles) with a mobile phase of 10 mM ammonium formate buffer
(pH 3.5)-methanol (25:75, v/v) and quantified by MS/MS detection in ESI positive
ion mode. The flow rate of the mobile phase was 200 MUL/min and the retention
times of tamsulosin and the internal standard (IS, diphenhydramine) were 0.8 and
0.9 min, respectively. The calibration curves were linear over a range of 0.01-20
ng/mL (r>0.999). The lower limit of quantification using 500 MUL of human plasma
was 0.01 ng/mL. The mean accuracy and precision for intra- and inter-day
validation of tamsulosin were both within acceptable limits. The present LC-MS/MS
method showed improved sensitivity for quantification of tamsulosin in human
plasma compared with previously described analytical methods. The validated
method was successfully applied to a pharmacokinetic study in humans.
PMID- 23153647
TI - Molecularly imprinted solid phase extraction of urinary diethyl thiophosphate and
diethyl dithiophosphate and their analysis by gas chromatography-mass
spectrometry.
AB - An analytical method involving molecularly imprinted solid phase extraction
(MISPE) and gas chromatography-mass spectrometry (GC-MS) was developed for the
analysis of organophosphates metabolites (diethyl thiophosphate--DETP and diethyl
dithiophosphate - DEDTP) in human urine samples. A DETP molecularly imprinted
polymer (MIP) was synthesized using 4-vinylpiridine as the functional monomer and
ethylene glycol dimethacrylate as the cross-linker. The conditioning step of the
MISPE was conducted by running 3 mL of acetonitrile, 3 mL of 0.1 mol L-1 dibasic
phosphate buffer at pH 11 and 2 mL of water through the molecularly imprinted
polymer (MIP) cartridge. The extraction step was executed using 1.0 mL of a urine
sample, with the pH previously adjusted to 3.0. Finally, the analytes were eluted
with 3 mL of acetonitrile and derivatized with 3% 2,3,4,5,6-pentafluorobenzyl
bromide solution at room temperature for 1h. The sample was analyzed by GC-MS in
the SIM (selected ion monitoring) mode. Analytical calibration curves for DETP
and DEDTP were constructed using a pool of urine samples and six levels of
concentration. The method was found to be linear from 10 to 500 MUg L-1 (r>0.99)
with limits of quantification of 10 MUg L-1 for both analytes. The within-day and
between-day precisions were evaluated (as %RSD) and all the results were <15% for
both analytes. The method was accurate (relative error<+/-15%), with good
robustness.
PMID- 23153648
TI - Extension of the survival dimensionality reduction algorithm to detect epistasis
in competing risks models (SDR-CR).
AB - BACKGROUND: The discovery and the description of the genetic background of common
human diseases is hampered by their complexity and dynamic behavior. Appropriate
bioinformatic tools are needed to account all the facets of complex diseases and
to this end we recently described the survival dimensionality reduction (SDR)
algorithm in the effort to model gene-gene interactions in the context of
survival analysis. When one event precludes the occurrence of another event under
investigation in the 'competing risk model', survival algorithms require
particular adjustment to avoid the risk of reporting wrong or biased conclusions.
METHODS: The SDR algorithm was modified to incorporate the cumulative incidence
function as well as an adapted version of the Brier score for mutually exclusive
outcomes, to better search for epistatic models in the competing risk setting.
The applicability of the new SDR algorithm (SDR-CR) was evaluated using synthetic
lifetime epistatic datasets with competing risks and on a dataset of scleroderma
patients. RESULTS/CONCLUSIONS: The SDR-CR algorithms retains a satisfactory power
to detect the causative variants in simulated datasets under different scenarios
of sample size and degrees of type I or type II censoring. In the real-world
dataset, SDR-CR was capable of detecting a significant interaction between the IL
1alpha C-889T and the IL-1beta C-511T single-nucleotide polymorphisms to predict
the occurrence of restrictive lung disease vs. isolated pulmonary hypertension.
We provide an useful extension of the SDR algorithm to analyze epistatic
interactions in the competing risk settings that may be of use to unveil the
genetic background of complex human diseases. AVAILABILITY:
http://sourceforge.net/projects/sdrproject/files/.
PMID- 23153649
TI - Pyrexia and neurologic outcomes after therapeutic hypothermia for cardiac arrest.
AB - OBJECTIVE: Therapeutic hypothermia, also known as targeted temperature management
(TTM), improves clinical outcomes in patients resuscitated from cardiac arrest.
Hyperthermia after discontinuation of active temperature management ("rebound
pyrexia") has been observed, but its incidence and association with clinical
outcomes is poorly described. We hypothesized that rebound pyrexia is common
after rewarming in post-arrest patients and is associated with poor neurologic
outcomes. METHODS: Retrospective multicenter US clinical registry study of post
cardiac arrest patients treated with TTM at 11 hospitals between 5/2005 and
10/2011. We assessed the incidence of rebound pyrexia (defined as temperature >38
degrees C) in post-arrest patients treated with TTM and subsequent clinical
outcomes of survival to discharge and "good" neurologic outcome at discharge,
defined as cerebral performance category (CPC) 1-2. RESULTS: In this cohort of
236 post-arrest patients treated with TTM, mean age was 58.1 +/- 15.7 y and
106/236 (45%) were female. Of patients who survived at least 24h after TTM
discontinuation (n=167), post-rewarming pyrexia occurred in 69/167 (41%), with a
median maximum temperature of 38.7 (IQR 38.3-38.9). There were no significant
differences between patients experiencing any pyrexia and those without pyrexia
regarding either survival to discharge (37/69 (54%) v 51/98 (52%), p=0.88) or
good neurologic outcomes (26/37 (70%) v 42/51 (82%), p=0.21). We compared
patients with marked pyrexia (greater than the median pyrexia of 38.7 degrees C)
versus those who experienced no pyrexia or milder pyrexia (below the median) and
found that survival to discharge was not statistically significant (40% v 56%
p=0.16). However, marked pyrexia was associated with a significantly lower
proportion of CPC 1-2 survivors (58% v 80% p=0.04). CONCLUSIONS: Rebound pyrexia
occurred in 41% of TTM-treated post-arrest patients, and was not associated with
lower survival to discharge or worsened neurologic outcomes. However, among
patients with pyrexia, higher maximum temperature (>38.7 degrees C) was
associated with worse neurologic outcomes among survivors to hospital discharge.
PMID- 23153650
TI - Early antibiotics improve survival following out-of hospital cardiac arrest.
AB - INTRODUCTION: Therapeutic hypothermia (TH) has become standard management
following out of hospital cardiac arrest (OHCA). Recent evidence suggests TH
increases the incidence of pneumonia. We retrospectively assessed infective
indicators after OHCA and evaluated the effect of antibiotics on survival.
METHOD: We identified all patients admitted to the ICU of a regional primary
angioplasty hospital following OHCA from May 2007 to December 2010. We collected
demographic and outcome data, evidence of infection and the use of antimicrobial
therapy. RESULTS: 138 patients were admitted to ICU following OHCA. The mortality
rate was 68.1% with mean ICNARC predicted mortality of 77.5%. Of 138 patients,
135 (97.8%) had at least one positive marker of infection within 72 h. 53 of 138
patients (38.4%) received antibiotics during the first 7 days of their ICU stay.
The hospital mortality rate for these patients was significantly less than those
not receiving antibiotics (56.6% vs. 75.3%; p=0.025) with NNT of 5. Multivariate
analysis demonstrated that antibiotic use was an independent predictor of
survival. CONCLUSION: The post-arrest management of OHCA is commonly complicated
by infections, the accurate diagnosis of which is impaired by the associated
increase in inflammatory markers, body temperature control, delay in the
processing of samples and poor quality chest radiography. We have shown a
significant reduction in mortality in patients who received antibiotics compared
with patients who did not. This suggests that a formal clinical trial is
warranted.
PMID- 23153651
TI - D-Aspartic acid implication in the modulation of frog brain sex steroid levels.
AB - There is evidence that D-aspartate (D-Asp) modulates sex hormone levels in frog
testis by regulating the activity of P450 aromatase (P450 aro), the key enzyme
which converts Testosterone (T) in 17beta-Estradiol (E2). Here we report, for the
first time, that there is a direct correlation among brain levels of D-Asp, P450
aro, E2 and Estradiol Receptor (ERalpha) in the male frogs during the
reproductive as well as the post-reproductive phases of the breeding cycle, with
highest levels being observed in the post-reproductive period. D-Asp i.p.
administration to frogs ready for reproduction, induced an increase of brain P450
aro protein expression with concomitant enhancement of both E2 levels and ERalpha
expression; at the same time, brain T levels and Androgen receptor expression
decreased. In contrast, in the post-reproductive frogs, D-Asp treatment did not
modify any of these parameters. Taken together, these results imply that the
regulation of P450 aro expression by D-Asp could be an important step in the
control of E2 levels in the frog brain.
PMID- 23153652
TI - Physiologic implications of inter-hormonal interference in fish: lessons from the
interaction of adrenaline with cortisol and thyroid hormones in climbing perch
(Anabas testudineus Bloch).
AB - Adrenaline and cortisol, the major stress hormones, are known for its direct
control on stress response in fish. Likewise, as an important stress modifier
hormone, thyroid hormone has also been implicated in stress response of fish. We
tested whether the hypothesis on the phenomenon of inter-hormonal interference, a
process that explains the hormonal interactions, operates in fish particularly
between adrenaline, cortisol and thyroid hormones. To achieve this goal, indices
of acid-base, osmotic and metabolic regulations were quantified after adrenaline
challenge in propranolol pre-treated air-breathing fish (Anabas testudineus).
Short-term adrenaline (10 ng g(-1)) injection for 30 min produced a rise in
plasma cortisol without affecting plasma T(3) and T(4). On the contrary, blocking
of adrenaline action with a non-selective blocker, propranolol (25 ng g(-1)) for
90 min reduced plasma cortisol along with plasma T(4) and that indicate a
possible interference of these hormones in the absence of adrenaline challenge.
Similarly, a reduction in plasma T(3) was found after adrenaline challenge in
propranolol pre-treated fish and that suggests a functional synergistic
interference of adrenaline with T(3). Adrenaline challenge in these fish,
however, failed to abolish this propranolol effect. The remarkable systemic
hypercapnia and acidosis by propranolol pre-treatment were reversed by adrenaline
challenge, pointing to a direct action of adrenaline on acid-base indices
probably by a mechanism which may not require beta-adrenergic receptor systems.
Interestingly, the prominent adrenaline-induced hyperglycemia, hyperlactemia and
hyperuremea were not altered by propranolol treatment. Similarly, adrenaline
challenge promoted and propranolol reduced the osmotic competencies of the gills,
kidneys and liver of this fish as evident in the sodium and proton pump
activities. The modified physiologic actions of adrenaline and its modified
interaction with THs and cortisol in blocked fish indicate an interaction of
adrenaline with cortisol and THs. Our physiologic evidences thus support the
hypothesis of the phenomenon of inter-hormonal interference.
PMID- 23153653
TI - Nitric oxide rectifies acid-base disturbance and modifies thyroid hormone
activity during net confinement of air-breathing fish (Anabas testudineus Bloch).
AB - Nitric oxide (NO), a short-lived freely diffusible radical gas that acts as an
important biological signal, regulates an impressive spectrum of physiological
functions in vertebrates including fishes. The action of NO, however, on thyroid
hormone status and its role in the integration of acid-base, osmotic and
metabolic balances during stress are not yet delineated in fish. Sodium
nitroprusside (SNP), a NO donor, was employed in the present study to investigate
the role of NO in the stressed air-breathing fish Anabas testudineus. Short-term
SNP treatment (1 mM; 30 min) interacted negatively with thyroid axis, as evident
in the fall of plasma thyroxine in both stressed and non-stressed fish. In
contrast, the cortisol responsiveness to NO was negligible. SNP challenge
produced systemic alkalosis, hypocapnia and hyperglycemia in non-stressed fish.
Remarkable acid-base compensation was found in fish kept for 60 min net
confinement where a rise in blood pH and HCO(3) content occurred with a reduction
in PCO(2) content. SNP challenge in these fish, on the contrary, produced a rise
in oxygen load together with hypocapnia but without an effect on HCO(3) content,
indicating a modulator role of NO in respiratory gas transport during stress
response. SNP treatment reduced Na(+), K(+) ATPase activity in the gill,
intestine and liver of both stressed and non-stressed fish, and this suggests
that stress state has little effect on the NO-driven osmotic competence of these
organs. On the other hand, a modulatory effect of NO was found in the kidney
which showed a differential response to SNP, emphasizing a key role of NO in
kidney ion transport and its sensitivity to stressful condition. H(+)-ATPase
activity, an index of H(+) secretion, downregulated in all the organs of both non
stressed and stressed fish except in the gill of non-stressed fish and this
supports a role for NO in promoting alkalosis. The data indicate that, (1) NO
interacts antagonistically with T(4), (2) modifies respiratory gas transport and
(3) integrates acid-base and osmotic actions during stress response in air
breathing fish. Collectively, this first evidence in fish indicate that NO can
promote compensatory physiologic modification and that can reduce the magnitude
of stress-induced acid-base and osmotic disturbance and that suggests a role for
NO in the ease and ease response of this fish.
PMID- 23153654
TI - Analysis of the relationships between evolvability, thermodynamics, and the
functions of intrinsically disordered proteins/regions.
AB - The evolvability of proteins is not only restricted by functional and structural
importance, but also by other factors such as gene duplication, protein
stability, and an organism's robustness. Recently, intrinsically disordered
proteins (IDPs)/regions (IDRs) have been suggested to play a role in facilitating
protein evolution. However, the mechanisms by which this occurs remain largely
unknown. To address this, we have systematically analyzed the relationship
between the evolvability, stability, and function of IDPs/IDRs. Evolutionary
analysis shows that more recently emerged IDRs have higher evolutionary rates
with more functional constraints relaxed (or experiencing more positive
selection), and that this may have caused accelerated evolution in the flanking
regions and in the whole protein. A systematic analysis of observed stability
changes due to single amino acid mutations in IDRs and ordered regions shows that
while most mutations induce a destabilizing effect in proteins, mutations in IDRs
cause smaller stability changes than in ordered regions. The weaker impact of
mutations in IDRs on protein stability may have advantages for protein
evolvability in the gain of new functions. Interestingly, however, an analysis of
functional motifs in the PROSITE and ELM databases showed that motifs in IDRs are
more conserved, characterized by smaller entropy and lower evolutionary rate,
than in ordered regions. This apparently opposing evolutionary effect may be
partly due to the flexible nature of motifs in IDRs, which require some key amino
acid residues to engage in tighter interactions with other molecules. Our study
suggests that the unique conformational and thermodynamic characteristics of
IDPs/IDRs play an important role in the evolvability of proteins to gain new
functions.
PMID- 23153655
TI - Neurological exotropia: do we need to decrease surgical dosing?
PMID- 23153657
TI - Grid laser photocoagulation for macular oedema due to branch retinal vein
occlusion in the age of bevacizumab? Results of a prospective study with
crossover design.
AB - BACKGROUND AND AIM: To investigate the long term effectiveness of grid laser
photocoagulation (GLP) versus intravitreal bevacizumab (BEV) in macular oedema
(MO) secondary to branch retinal vein occlusion (BRVO), and to evaluate the
treatment courses after treatments were switched. METHODS: In this prospective
interventional consecutive case series, previously untreated eyes with perfused
MO were enclosed over a period of 16 months for BEV and for 29 months for GLP.
The follow-up period was 1 year. Patients with persistent MO after 12 months of
BEV were offered GLP and vice versa, and were followed-up for another 12 months.
RESULTS: Both BEV (23 eyes) and GLP (21 eyes) caused a significant (p<0.05)
reduction in central retinal thickness (CRT) at 12 months although this was
delayed with GLP. However, BEV revealed a significantly better best corrected
visual acuity (BCVA) compared with GLP (0.2 vs 0.5 logMAR; p<0.04). Switching
therapy for non-responders revealed a reduced CRT at another 12 months, although
this was not significant. CONCLUSIONS: Functionally and anatomically, BEV appears
to be more effective than GLP for the therapy of MO due to BRVO. BCVA is
significantly better after 1 year and the anatomical response of the MO is
faster. Furthermore, non-responders with persistent MO despite BEV or GLP
treatment might benefit from switching therapy.
PMID- 23153658
TI - Clinical and molecular features in patients with advanced non-small-cell lung
carcinoma refractory to first-line platinum-based chemotherapy.
AB - Most of the cases of non-small-cell lung cancer (NSCLC) are diagnosed at an
advanced stage and are treated with platinum-doublet chemotherapy. However, some
patients are refractory to this treatment. The aim of this study was to identify
the clinical and molecular characteristics of patients with refractory disease.
All consecutive patients between 2003 and 2006, who received a platinum-doublet
chemotherapy as first-line treatment for stage IIIb-IV NSCLC, were included.
Refractory patients were defined as early progressive disease (PD) at the first
evaluation of chemotherapy according to WHO criteria. The clinical, histo
pathological, and molecular characteristics (EGFR: exon 19, 20, 21 and KRAS: exon
2 by PCR sequencing; ALK by immunohistochemistry) and survival of refractory
patients with initial PD (r-patients) and controlled disease (c-patients) were
compared by univariate analyses. Factors that differed between the two groups (p
value <0.25 in univariate analyses) were entered into multivariate analysis. In
this study, 178 patients were included. The first tumor assessment was carried
out after a median of three cycles (range 1-4). Forty-six (25.8%) patients were
refractory. Clinical presentation was similar between r- and c-patients. The
sarcomatoid histological subtype was more common in r-patients than c-patients
(10.9% vs. 1.5%, respectively; p=0.057). The proportion of EGFR (5.2% vs. 9.6%,
p=0.224) and KRAS mutations (11.1% vs. 5.7%, p=0.357), and the expression of ALK
(6.3% vs. 2.5%, p=0.327) did not differ significantly between the two groups. In
multivariate analysis, sarcomatoid histological subtype was the only factor
associated with early PD (OR=7.50; 95%CI: 1.02-55.45; p=0.048). r-Patients had
significantly shorter survival than c-patients (median 5 months (IQR 3.2-9.9) vs.
15.4 months (IQR 9.9-22.5), respectively; p<0.0001). In conclusion, patients with
early PD under platinum-doublet chemotherapy had shorter survival than c
patients. Sarcomatoid histological subtype was the only independent factor
associated with early PD.
PMID- 23153659
TI - The influence of time of radio-chemotherapy and other therapeutic factors on
treatment results in patients with limited disease small cell lung cancer.
AB - PURPOSE: The evaluation of effect of therapeutic parameters such as time of
starting thoracic radiotherapy in relation to chemotherapy, schedule of
combination chemo- and radiotherapy and SER, on treatment results in patients
with limited disease small cell lung cancer (LD SCLC). METHODS: Between 2000 and
2007, 212 patients with LD SCLC received combined therapy: chemotherapy and
thoracic radiotherapy. All patients received chemotherapy according to PE
schedule (4-6 cycles), in combination with thoracic radiotherapy. The total dose
applied to GTV was 54 Gy given in 27-30 fractions using fraction dose of 1.8-2.0
Gy. The concurrent treatment was performed in 112 patients (52.8%): the
conventional fractionation (once a day, every five days a week) in 35 patients
while 77 patients received "moderate" accelerated fractionation (one fraction a
day, every four days a week and two fractions within one day, a week apart, with
6h gap). The remaining 100 patients (47.2%) received sequential treatment. The
time from the first day of chemotherapy to the end of thoracic radiotherapy (SER)
was evaluated in all patients. The SER ranged from 57 to 337 days with the median
value of 121 days. RESULTS: The complete response in the thorax was observed in
143 out of 212 patients (67.5%). Out of these, 82 patients received concurrent
chemo-radiotherapy (given in 22 patients as conventional dose fractionation and
in 60 patients according to "moderate" accelerated dose fractionation), and the
remaining 61 patients were treated with sequential therapy. The 5-year survival
rates were: 17.7% for overall survival (OS), and 19.3% for disease-free survival
(DFS). The relationship of therapeutic factors to survival rates showed
statistically significant improvement of survival ratios in relation to early
starting of thoracic radiotherapy and application of concurrent chemo
radiotherapy. The results of logistic regression revealed significant
relationship between the value of SER and OS and DFS. The analysis shows that
each day of extension of the SER resulted in increased probability of death
(decrease of OS) by 0.28% and in increased the risk of development failure
(decrease of DFS) by 0.31%. The influence of SER on lowered probability of
complete response frequency was not statistically significant. CONCLUSIONS: The
concurrent chemo-radiotherapy with early administration of thoracic radiotherapy,
results in improved complete response in the thorax and increase of overall and
disease-free survival rates. The 5-year survival rates were: 17.7% for overall
survival and 19.3% for disease-free survival. Our analysis and data from the
literature suggest that shorter SER may play prognostic role in patients with LD
SCLC treated with combination chemo- and radiotherapy. However, these
observations require the confirmation in following studies.
PMID- 23153660
TI - Comparative multidatabase analysis of dosing patterns and infusion intervals for
the first 12 infliximab infusions in patients with rheumatoid arthritis.
AB - BACKGROUND: According to prescribing information for rheumatoid arthritis (RA)
treatments in the United States, infliximab should be administered at weeks 1, 2,
6, and then every 8 weeks starting at a 3-mg/kg dose, with flexible dosing up to
10 mg/kg and/or every 4 weeks based on clinical response. OBJECTIVE: This study
evaluated dosing and intervals of the first 12 infliximab infusions in patients
with RA across multiple large administrative databases. METHODS: Data were
obtained from 4 databases: HealthCore Integrated Research Database (HIRD), IMS
LifeLink Health Plan Claims Database (IMS Lifelink), Premier Perspective Database
(PPD), and Wolters Kluwer Pharma Solutions (WKPS). Patients were aged >=18 years,
diagnosed with RA, and naive to biologic therapy. Patients with other select
inflammatory conditions were excluded. The induction period included infusions 1
through 3; the maintenance period included infusions 4 through 12. RESULTS:
Observed dosing patterns from the HIRD, IMS LifeLink, PPD, and WKPS databases
demonstrated minimal dose increases from the first infusion (93.5, 103.3, 58.8,
and 73.2 mg, respectively) and from the first maintenance infusion (69.1, 64.3,
45.7, and 45.7 mg, respectively) to the highest dose during the first 12
infusions. The mean number of days between infusions in the maintenance period
ranged from 53.3 to 63.5 in HIRD, 53.7 to 60.3 in IMS LifeLink, 53.4 to 59.4 in
PPD, and 52.3 to 55.0 in the WKPS database. CONCLUSION: Data from multiple
databases of patients with RA suggest that, in clinical practice, infliximab
dosing and intervals are consistent with FDA prescribing information and remain
relatively stable during the first 12 infusions.
PMID- 23153661
TI - Limited sampling estimates of epigallocatechin gallate exposures in cirrhotic and
noncirrhotic patients with hepatitis C after single oral doses of green tea
extract.
AB - BACKGROUND: Epigallocatechin-3-gallate (EGCG) has antiangiogenic, antioxidant,
and antifibrotic properties that may have therapeutic potential for the treatment
of cirrhosis induced by hepatitis C virus (HCV). However, cirrhosis might affect
EGCG disposition and augment its reported dose-dependent hepatotoxic potential.
OBJECTIVE: The safety, tolerability, and disposition of a single oral dose of
EGCG in cirrhotic patients with HCV were examined in an exploratory fashion.
METHODS: Eleven patients with hepatitis C and detectable viremia were enrolled.
Four had Child-Pugh (CP) class A cirrhosis, 4 had Child-Pugh class B cirrhosis,
and 3 were noncirrhotic. After a single oral dose of green tea extract 400 mg
containing 94% pure EGCG, blood for EGCG levels and safety parameters was
ascertained at 2, 4, and 10 hours. RESULTS: C(max) and AUC to EGCG overlapped
among the 3 groups, which suggests that the disposition of EGCG was not
significantly altered in these patients with cirrhosis. CONCLUSIONS: A single 400
mg oral dose of EGCG was safe and well tolerated by all of the patients in the
study. These results provide guidance for the continued investigation of the long
term safety and antitumor potential of EGCG in cirrhotic patients with HCV.
PMID- 23153662
TI - Current twin studies in Germany: report on CoSMoS, SOEP, and ChronoS.
AB - This article summarizes the status of three recent German twin studies: CoSMoS,
SOEP, and ChronoS. The German twin study on Cognitive Ability, Self-Reported
Motivation, and School Achievement (CoSMoS) is a three-wave longitudinal study of
monozygotic and dizygotic twins reared together, and aims to investigate
predictors of and influences on school performance. In the first wave of the data
collection in 2005, 408 pairs of twins aged between 7 and 11 as well as their
parents participated in CoSMoS. The SOEP twin study is an extended twin study,
which has combined data from monozygotic and dizygotic twins reared together with
additional data from full sibling pairs, mother-child, and grandparent-child
dyads who participated in the German Socio-Economic Panel (GSOEP) study. The SOEP
twin project comprises about 350 twin and 950 non-twin pairs aged between 17 and
70. Data were collected between 2009 and 2010, with a focus on personality
traits, wellbeing, education, employment, income, living situation, life
satisfaction, and several attitudes. The aim of the Chronotype twin study
(ChronoS) was to examine genetic and environmental influences on chronotype
(morningness and eveningness), coping strategies, and several aspects of the
previous SOEP twin project in a sample of 301 twin pairs aged between 19 and 76
years, recruited in 2010 and 2011. Part of the ChronoS twin sample also
participated in the earlier SOEP twin study, representing a second wave of
assessments. We briefly describe the design and contents of these three studies
as well as selected recent findings.
PMID- 23153663
TI - Natural history of partial anterior cruciate ligament tears: a systematic
literature review.
AB - INTRODUCTION: Partial anterior cruciate ligament (ACL) tear is frequent, and
indications for surgery may be raised by a diagnostic aspect associating slight
laxity with no clear pivot-shift. Unlike that of complete ACL tear, the natural
history of partial tear remains controversial. MATERIAL AND METHOD: A systematic
literature review searched for referenced publications on the natural history of
partial ACL tear. Twelve specific articles were retrieved. Initial diagnosis was
systematically confirmed on arthroscopy, without ACL surgery. The following
criteria were analyzed: firstly, preoperative: confirmation of inclusion
criteria, preoperative clinical data, follow-up, arthroscopic lesion assessment,
Lachman test, Pivot shift test, hemarthrosis, associated lesions and secondly,
follow-up: Lachman test, Pivot shift test, revision surgery, functional clinical
scores, pain, sport and return to sport, meniscal events. RESULTS:
Preoperatively, Lachman tests were positive (soft or delayed) in a mean 49.7% of
cases (range, 0-100%); pivot shift test was systematically negative. At a mean
5.2 years' follow-up, Lachman test was "positive" in 47.6% of cases (range, 38
59%), with positive pivot shift test in 26.3% (range, 5-51%). 54.3% patients
reported pain (range, 36-64%), and mean Lysholm score was 88.4 (17-100%). Fifty
two percent (21-60%) of patients resumed sport at their previous level.
DISCUSSION/CONCLUSION: The natural history of non-operated partial ACL tear is
good over the medium term, especially if patients limit their sports activities.
The greater the functional instability, the more frequent is residual pain.
Laxity, although not quantified, seems to progress with time, with a positive
pivot shift test emerging in a quarter of cases. Functional management may be
recommended in non-athletic patients without meniscal lesion, but surgical
treatment may be recommended in other patients. Indications for ACL
reconstruction are thus the same in partial as in complete tear.
PMID- 23153664
TI - Salvage technique for postoperative infection and necrosis of the Achilles
tendon.
AB - Surgery of the Achilles tendon is associated with postoperative morbidity related
to wound healing. Necrotic infection of the tendon is a rare but serious
complication that may be associated with increasingly invasive surgical
treatments using various free flap transfers proposed in the literature. Dealing
with this complication, we prefer the technique of managed wound healing
suggested by Dautry. The surgical procedure includes radical debridement of the
infected tissue and necrotic Achilles tendon followed by managed wound healing
with daily irrigation. Fifteen cases were treated between 1994 and 2003. Healing
was achieved after 30 to 100 days. MRI results show scar tissue continuity
suggesting a neotendon formation. Function was very satisfactory in 9/15 ankles.
The salvage technique presented here for cases of infection and necrosis of the
Achilles tendon is simple with low morbidity and results in effective wound and
tendon healing with satisfactory functional and anatomical results.
PMID- 23153665
TI - Current concept in rotational laxity control and evaluation in ACL
reconstruction.
AB - Rotation combined with translation; compose the three-dimensional motion of the
knee subluxation in anterior cruciate ligament deficient knee. The worldwide
scientists were focused initially on the translation part of this complex 3D
motion, but since the beginning of the century there was a large interest on knee
rotational laxity study. Lot of paper reported new devices and results with an
explosion since the beginning of the decade. The purpose of this review is to
provide an extensive critical analysis of the literature and clarify the
knowledge on this topic. We will start with a dismemberment of different
rotational laxities reported: the rotation coupled with translation in 2D tests
such as Lachman test and anterior drawer test; the rotational envelope
considering the maximum internal external rotation; and the "active rotation"
occurring in 3D Pivot-shift (PS) test. Then we will analyze the knee kinematics
and the role of different anterior cruciate ligament (ACL) bundle on rotation. A
review of different mechanical and radiological devices used to assess the
different rotations on ACL deficient knees will be presented. Two groups will be
analyzed, dynamic and static conditions of tests. Navigation will be described
precisely; it was the starter of this recent interest in rotation studies. Opto
electronic and electromagnetic navigation systems will be presented and analyzed.
We will conclude with the last generation of rotational laxity assessment
devices, using accelerometers, which are very promising.
PMID- 23153666
TI - The role of fibular fixation in the treatment of tibia diaphysis distal third
fractures.
AB - INTRODUCTION: Combined fractures of the distal third of tibia diaphysis and
fibula diaphysis are a common orthopedic injury. There is an ongoing debate about
the necessity of fibular fixation when associated to distal third tibial
fracture. This study aims at evaluating the role of fibular fixation in the
treatment of distal third tibial fractures. HYPOTHESIS: We hypothesized that
fixation of the fibula increases the stability of fixation in distal third tibial
and fibular fractures. MATERIALS AND METHODS: In a randomized clinical trial, 53
patients with concomitant fractures of tibia and ipsilateral fibula at distal
third level were recruited in this study during a 23-month period. Patients were
randomized in two groups: patients with fibular fixation (case group) and without
fibular fixation (control group). The patients were followed up for at least 6
months postoperatively. RESULTS: There were seven cases exhibiting malalignment
on immediate postoperative radiographs. Six of them were in group II (control
group) and one was in group I (case group) (P=0.084). We didn't find nonunion in
group I and we found three patients in group II (P=0.141). Infection was one in
group I and two in group II on gustillo II injuries (P=0.516). CONCLUSION:
Despite its low count of patients, our study didn't show any advantage to fix the
fibula fracture associated to distal third of tibia diaphysis fracture. It didn't
show either an increase of complication after fibula open reduction and internal
fixation. LEVEL OF EVIDENCE: Level III. Randomized prospective study.
PMID- 23153667
TI - Arthroscopic repair of subscapularis tears: preliminary data from a prospective
multicentre study.
AB - BACKGROUND: Until the introduction of arthroscopic-assisted surgery for rotator
cuff repair, the frequency of subscapularis tears was underestimated. These tears
remain challenging to treat even with arthroscopy. The absence of a specific
classification system has hampered communication about the treatment and outcomes
of the various types of subscapularis tears. The objective of this prospective
multicentre study was to validate the relevance of arthroscopic subscapularis
tendon repair based on an assessment of short-term outcomes according to the
initial extent of the anatomic lesions. METHODS: A prospective multicentre study
sponsored by the French Society for Arthroscopy was conducted from March 2010 to
January 2011 in 208 patients with subscapularis lesions that were either isolated
or associated with limited anterosuperior tears. The Constant and UCLA scores
were used to assess clinical outcomes. Anatomic and prognostic results were
evaluated based on the physical examination, preoperative and postoperative
imaging study findings, and anatomic lesions. Clinical data were available for
103 patients after at least 1 year of follow-up and radiological data for 129
patients after at least 6 months. RESULTS: The preliminary clinical results in
103 patients with at least 1 year of follow-up showed overall statistically
significant improvements in the Constant and UCLA scores, with resolution of the
clinical manifestations. The degree of improvement seemed to increase over time.
The clinical results varied significantly across patient groups based on a
classification system distinguishing four lesion types. Postoperative imaging
studies to assess the anatomic results in all patients with at least 6 months of
follow-up (n=129) showed tendon healing in 92% of cases but also indicated muscle
wasting of the upper subscapularis muscle in 18.6% of cases and increased fatty
degeneration of the muscle belly. DISCUSSION: Our study confirms the good
clinical and radiological results reported in the literature. Our classification
system distinguishing four lesion patterns was applicable during the imaging
workup. The main finding from this classification system was the difference in
results between Type 2 and Type 3 lesions. The trend towards improvements over
time requires confirmation by longer-term studies, which will also have to
establish that the increased wasting of the upper subscapularis muscle and fatty
degeneration of the muscle belly have no adverse effects.
PMID- 23153668
TI - Retinal drug delivery using eyedrop preparations of poly-L-lysine-modified
liposomes.
AB - The purpose of this study was to develop surface-modified liposomes that enhance
the efficiency of eye drop drug delivery to the retina. Various molecular weights
and concentrations of the water-soluble cationic polymer poly-L-lysine (PLL) were
used to modify the surface of submicronized (100 nm) liposomes. Physicochemical
properties of surface-modified liposomes were determined in vitro, and the
efficiency of drug delivery to the retina was investigated in vivo. Using
coumarin-6 as a model drug and fluorescent marker, we show that liposome surface
modification by PLL dramatically increased delivery to mouse retina segments
after eye drop administration. However, when PLL of high molecular weight
(>30,000) was used at higher concentrations (>0.05%), aggregation of surface
modified liposomes increased particle size and hampered distribution to inner
ocular tissues. As a result, the efficiency of drug delivery of these aggregated
surface-modified liposomes was the same as unmodified liposomes. The optimal
molecular weight and concentration of PLL in drug-delivering liposomes were
15,000-30,000 and 0.005%, respectively. Under these conditions, PLL-modified
liposomes were not cytotoxic in corneal or conjunctival cells. In conclusion,
surface-modified liposomes have great potential as effective retinal drug
delivery carriers in eye drop formulations.
PMID- 23153669
TI - Production of nanoparticles-in-microparticles by a double emulsion method: a
comprehensive study.
AB - A method based on a double emulsion system (solid-in-water-in-oil-in-water) has
been developed for the production of nanoparticles-in-microparticles (NIMs). The
distribution of nanoparticles within the NIMs was explored using light and
electron microscopy and through assessment of drug loading and release profiles.
The extent of nanoparticle entrapment within the NIMs was found to be dependent
on the state (wet vs. dry) in which the nanoparticles were introduced to the
formulation. The technique was readily adaptable to produce NIMs of different
morphologies. It is proposed that NIMs and this method to produce them have broad
application in drug delivery research.
PMID- 23153670
TI - Influence of polymeric microcarriers on the in vivo intranasal uptake of an anti
migraine drug for brain targeting.
AB - The objective of this study was to investigate the effect of polymeric
microcarriers on the in vivo intranasal uptake of an anti-migraine drug for brain
targeting. Mucoadhesive powder formulations consisted of antimigraine drug,
zolmitriptan, and chitosans (various molecular weights and types) or
hydroxypropyl methylcellulose (HPMC). Their suitability for nasal administration
was evaluated by in vitro and ex vivo mucoadhesion and permeation tests. The
formulations based on chitosan glutamate (CG) or HPMC were tested in vivo because
they showed good mucoadhesive properties and altered the permeation rate of the
drug. The in vivo results from intravenous infusion and nasal aqueous suspension
of the drug or nasal particulate powders were compared. The plasmatic AUC values
obtained within 8h following intravenous administration appeared about three
times higher than those obtained by nasal administration, independent of the
formulations. Zolmitriptan concentrations in the cerebrospinal fluid obtained
from nasal and intravenous administrations were, respectively, 30 and 90 times
lower than the concentrations of the drug in the blood. Thus, nasal
administration potentiated the central zolmitriptan activity, allowing a
reduction in the drug peripheral levels, with respect to the intravenous
administration. Among nasally administered formulations, CG microparticles showed
the highest efficacy in promoting the central uptake of zolmitriptan within 1h.
PMID- 23153671
TI - An antioxidant regenerating system for continuous quenching of free radicals in
chronic wounds.
AB - A novel antioxidant regenerating system consisting of cellobiose dehydrogenase
(CDH), cellobiose, and phenolic antioxidants with potential application for
continuous quenching of free radical species in chronic wounds was developed.
This antioxidant regenerating system, continuously quenched in situ produced .NO,
O(2)(.-) and OH. radicals and the produced oxidized phenolic antioxidants were
regenerated back to their original parent compounds by CDH using cellobiose as
electron donor. This system therefore prevented the accumulation of oxidized
phenolic antioxidants. Interestingly, this study also challenges the relevance of
using total antioxidant capacities values of plant crude extracts obtained using
biologically none relevant radical species like (2,2-diphenyl-1-picrylhydrazyl
(DPPH)), Trolox Equivalent Antioxidant Capacity (TEAC), etc. when applied as
medicinal remedies. This is because methoxylated phenolic antioxidants like
sinapic acid, ferulic acid; 2,6-dimethoxyphenol readily donate their electrons to
these radicals (DPPH, TEAC, etc.), thereby greatly influencing the total
antioxidant values although this study showed that they are not at all effective
in quenching O(2)(.-) radicals and again are not the most effective quenchers of
NO and OH radicals as demonstrated during this study.
PMID- 23153672
TI - Anaphylaxis: the great challenge.
PMID- 23153675
TI - Mental time travel: a case for evolutionary continuity.
AB - In humans, hippocampal activity responds to the imagining of past or future
events. In rats, hippocampal activity is tied to particular locations in a maze,
occurs after the animal has been in the maze, and sometimes corresponds to
locations the animal did not actually visit. This suggests that mental time
travel has neurophysiological underpinnings that go far back in evolution, and
may not be, as some (including myself) have claimed, unique to humans.
PMID- 23153673
TI - The association between skin collagen glucosepane and past progression of
microvascular and neuropathic complications in type 1 diabetes.
AB - PURPOSE: We determined the association between novel and acid-labile skin
collagen-linked advanced glycation endproducts (AGEs) and the progression of
microvascular and neuropathic complications from baseline to near study closeout
in the Diabetes Control and Complications Trial (DCCT). METHODS: From a skin
biopsy obtained near the close of the DCCT, proteolytic collagen digests were
analyzed by liquid chromatography/mass spectrometry (LC/MS/MS) for glucosepane
(GSPNE), glyoxal and methylglyoxal hydroimidazolones (G-H1 and MG-H1) and the
glycation product fructose-lysine (FL) using isotope dilution method. RESULTS:
GSPNE and MG-H1 correlated with age and diabetes duration (P<0.02), while GSPNE
and FL correlated with the history of glycemia expressed as mean A1c (P<=0.003).
Age and duration-adjusted GSPNE and FL levels were lower in intensive (INT) vs.
conventional (CONV) treatment subjects in the primary prevention DCCT cohort
(P<0.0001), and FL was lower in INT in the secondary intervention cohort
(P<0.0001). GSPNE was associated with increased incidence of retinopathy
progression (odds ratio (OR) / unit increase in GSPNE: 2.5 for 3 step progression
on the ETDRS scale, P=0.003) and sustained>=3 microaneurysms (MA) (OR=4.8,
P<0.0001) from DCCT baseline up to the time of the biopsy, and prevalence of
microalbuminuria or AER>40mg/24h (OR=5.3, P<0.0001), and confirmed clinical
neuropathy (OR=3.4, P=0.015) at the time of the biopsy. GSPNE adjusted for mean
A1c remained significant for >=3 MA (P=0.0252) and AER (P=0.0006). The strong
association of complications with A1c was reduced or eliminated when adjusted for
GSPNE. CONCLUSIONS: Glucosepane is a novel AGE marker of diabetic complications
that is robustly associated with nephropathic, retinopathic and neuropathic
outcomes despite adjustment for A1c, suggesting that it could be one mediator of
these complications with possible diagnostic implications.
PMID- 23153674
TI - Accumulation of tissue macrophages and depletion of resident macrophages in the
diabetic thymus in response to hyperglycemia-induced thymocyte apoptosis.
AB - AIMS: We investigated the dynamics and morphology of thymus macrophages in
response to thymus involution caused by hyperglycemia. Thymus is an organ
affected early and dramatically after the onset of diabetes, losing most of the
thymocyte populations but diabetes's impact on the components of the thymus
stroma is largely unknown. METHODS: Rats were injected with streptozotocin and
thymus weight, body weight, and glycemia were measured at various time points.
The dynamics and morphology of macrophages in the diabetic thymus were
investigated by histology, immunohistochemistry, qPCR, electron microscopy and
flow cytometry. RESULTS: In hyperglycemic animals the involuting thymus is
gradually infiltrated by tissue macrophages (ED1-positive) and depleted of
resident macrophages (ED2-positive). While ED1 positive macrophages are scattered
in both cortex and medulla the ED2 positive ones are limited to the cortex and
cortico-medullary junction. CD4+CD11b+macrophages also accumulate. The TUNEL
reaction that detects the degradation of the DNA from apoptotic thymocytes in the
macrophages is enhanced. The thymic macrophages enlarge and accumulate lipid
vacuoles and apoptotic bodies. qPCR measurements of the expression of macrophage
markers showed a persistent increase in the diabetic thymus after the injection
of streptozotocin. CONCLUSIONS: Thymus involutes rapidly and persistently after
the onset of hyperglycemia because of the elevated apoptosis in the thymocytes.
Tissue macrophages accumulate in the thymus and the resident macrophages
decrease. This results in an overall increase in macrophage activity in the
diabetic thymus in response to the elevated apoptosis of thymocytes produced by
hyperglycemia.
PMID- 23153676
TI - Characterization of hydroxyphenol-terminated alkanethiol self-assembled
monolayers: interactions with phosphates by chemical force spectrometry.
AB - Tannins and humic substances, commonly referred to as natural organic matter
(NOM), constitute an important component of natural water and soil systems. These
species contain numerous hydroxyl and carboxyl functional groups whose reactivity
is strongly dependent on both the quantity and location of these moieties on the
aromatic ring. In the present study, self-assembled monolayers (SAMs) of 4-(12
mercaptododecyl)benzene-1,2-diol (o-hydroxyphenol-terminated); 5-(12
mercaptododecyl)benzene-1,3-diol (m-hydroxyphenol-terminated); bis(11
thioundecyl) hydrogen phosphate (monoprotic phosphate); and 11-thioundecyl
dihydrogen phosphate (diprotic phosphate) were prepared and characterized using X
ray photoelectron spectroscopy (XPS), attenuated total reflectance infrared
spectroscopy (ATR-IR), and water contact angle measurements. The interactions
between phenolic groups with phosphates were examined as a function of pH using
the chemical force spectrometry (CFS) technique. The observations are discussed
in the context of hydrogen bonding and electrostatic repulsion interaction
between corresponding species. Adhesion force profiles of hydroxyphenol isomers
interacting with monoprotic phosphate are dominated by ionic H-bonding; however
the strength of o-hydroxyphenol interactions is significantly higher. The
difference in location of hydroxyl groups on the interface also results in
significantly different force-distance profiles for the isomeric hydroxyphenols
when interacting with diprotic phosphate.
PMID- 23153677
TI - Surface tension model for surfactant solutions at the critical micelle
concentration.
AB - A model for the limiting surface tension of surfactant solutions (surface tension
at and above the critical micelle concentration, cmc) was developed. This model
takes advantage of the equilibrium between the surfactant molecules on the
liquid/vacuum surface and in micelles in the bulk at the cmc. An approximate
analytical equation for the surface tension at the cmc was obtained. The derived
equation contains two parameters, which characterize the intermolecular
interactions in the micelles, and the third parameter, which is the surface area
per surfactant molecule at the interface. These parameters were calculated using
a new atomistic modeling approach. The performed calculations of the limiting
surface tension for four simple surfactants show good agreement with experimental
data (~30% accuracy). The developed model provides the guidance for design of
surfactants with low surface tension values.
PMID- 23153678
TI - Modeling the granule formation mechanism from single drop impact on a powder bed.
AB - Granule formation from drop impact on a powder bed can occur by either Tunneling
or Spreading/Crater Formation. The governing regime can be specified by the
experimentally determined modified Bond number (Bo(g)*), which is a ratio of the
capillary force to the gravitational force acting on a particle. It was
hypothesized that Tunneling would occur when the capillary and surface tension
forces exceeded the weight of a powder aggregate in contact with the drop. To
confirm this hypothesis, force balances were derived for a drop in contact with a
single particle and separately for a drop in contact with an aggregate to predict
when a particle or aggregate will be sucked into the drop. The force ratios
derived for each case were compared to the Bo(g)* force ratio used in a
previously published regime map that separates Tunneling from Spreading/Crater
Formation. The force balance model correctly predicts the trends of the impact of
powder and liquid properties on the governing regime. However, the single
particle model does not quantitatively predict the critical Bond number for
regime change in Tunneling. The aggregate model gave a better prediction of the
Tunneling boundary than the single particle model, but it still under predicts
the experimentally determined Tunneling criterion given by the Bond number.
Potential reasons for this discrepancy are discussed.
PMID- 23153679
TI - Interaction between oxalic acid and titania in aqueous ethanol dispersions.
AB - The charging effects resulting from adsorption of oxalic acid and oxalate anions
on titania (anatase) surfaces in anhydrous or mixed water-ethanol suspensions is
summarized. The suddenly enhanced electrical conductance with respect to titania
free solutions has previously been explained in terms of surface-induced
electrolytic dissociation (SIED) of weak acids. A recently published model has
previously been found to successfully characterize the complex SIED effect. The
model is evaluated experimentally by recording the conductance and pH of the
dispersion and the zeta potential of the particles. The experimental results can
be condensed to master curves, which reveal the major properties of the systems
and facilitate further modeling of extensive experimental results. The
equilibrium and transport properties of solutions and particles were related, but
different mechanisms was found to be active in each case. The results suggest
that at least three adsorption equilibria should be considered in order to
improve the model.
PMID- 23153680
TI - Adsorption of high ammonium nitrogen from wastewater using a novel ceramic
adsorbent and the evaluation of the ammonium-adsorbed-ceramic as fertilizer.
AB - A novel ceramic adsorbent was developed to adsorb ammonium from high
concentration ammonium contaminated wastewater. Typical gardening cultivation
mediums in Japan-Kanuma clay and Akadama clay were used to synthesize the ceramic
adsorbent. Static batch experiments were conducted to investigate the effect of
various parameters such as contact time, initial ammonium concentration,
adsorbent dosage, and competing cations during the ammonium adsorption process.
The results revealed that the Freundlich isotherm model fitted better with the
adsorption process than the Langmuir model, and the adsorption process was well
described by pseudo-second-order kinetic model. The maximum nitrogen adsorption
capacity of the ceramic adsorbent was 75.5 mg g(-1) at an initial NH(4)(+)-N
concentration of 10,000 mg L(-1), dosage of 20 g L(-1), and contact time of 480
min. Results demonstrated that the low-cost ceramic adsorbent directly used as
nitrogen fertilizer was feasible for its high ammonium nitrogen content, nontoxic
effect on the environment and excellent soil properties.
PMID- 23153681
TI - Nanoparticle gel electrophoresis: bare charged spheres in polyelectrolyte
hydrogels.
AB - Nanoparticle gel electrophoresis has recently emerged as an attractive means of
separating and characterizing nanoparticles. Consequently, a theory that accounts
for electroosmotic flow in the gel, and coupling of the nanoparticle and hydrogel
electrostatics and hydrodynamics, is required, particularly for gels in which the
mesh size is comparable to or smaller than the particle radii. Here, we present
an electrokinetic model for charged, spherical colloidal particles undergoing
electrophoresis in charged (polyelectrolyte) hydrogels: the gel-electrophoresis
analogue of Henry's theory for electrophoresis in Newtonian electrolytes. We
compare numerically exact solutions of the model with several independent
asymptotic approximations, identifying regions in the parameter space where these
approximations are accurate or break down. As previously assumed in the
literature, Henry's formula, modified by the addition of a constant
electroosmotic flow mobility, is accurate only for nanoparticles that are small
compared to the hydrogel mesh size. We derived an exact analytical solution of
the full model by judiciously modifying the theory of Allison et al. for
uncharged gels, drawing on the superposition methodology of Doane et al. to
account for hydrogel charge. This furnishes accurate and economical mobility
predictions for the entire parameter space. The present model suggests that
nanoparticle size separations (with diameters ?40 nm) are optimal at low ionic
strength, with a gel mesh size that is selected according to the particle
charging mechanism. For weakly charged particles, optimal size separation is
achieved when the Brinkman screening length is matched to the mean particle size.
PMID- 23153682
TI - Approach towards mild depression: shortest way to treat climacteric syndrome?
PMID- 23153683
TI - Effect of diabetes on endometrial cancer recurrence and survival.
AB - OBJECTIVE: The purpose of this study was to investigate the influence of diabetes
mellitus (DM) on cancer stage at diagnosis, cancer recurrence, and survival of
endometrial cancer (EC) patients and the influence of the treatment of EC on
glycaemic control, treatment, and complications of DM. METHODS: In this
retrospective cohort study all 1644 patients with EC newly diagnosed in 2000-2008
and recorded in the population-based Eindhoven Cancer Registry (ECR) were
included. In addition, from this total cohort a subcohort was selected for
additional data collection and analyses, including 193 EC patients with DM and an
age-matched sample of 195 EC patients without DM. Patients with FIGO stage IV as
well as non-endometrioid histology were excluded. RESULTS: In the total cohort EC
patients with DM had a significantly higher age (69 years vs. 64 years), higher
FIGO stages and more additional comorbidities compared to EC patients without DM.
The 5-year overall survival rate for EC patients with DM was significantly lower
than for EC patients without DM (68% vs. 84%). After adjusting for age, stage,
period of diagnosis, cardiovascular disease, and treatment, this significant
effect of DM on overall mortality persisted (HR 1.4, 95% CI: 1.0-1.8). Subcohort
analyses showed that EC patients with DM were diagnosed more often with a higher
body mass index (BMI) (34 kg/m(2) vs. 30 kg/m(2)) and EC was not significantly
associated with changes in DM characteristics over time. Although the 5-year
overall survival rate for EC patients with DM was significantly lower in the
subcohort, for EC-specific mortality (n=388) no statistically significant effect
of DM was observed after adjustment for FIGO stage (HR=1.7, 95% CI: 0.7-3.9).
CONCLUSIONS: EC patients with DM compared to those without had worse patient
characteristics, a higher FIGO stage, similar recurrence rates and worse overall
survival.
PMID- 23153684
TI - A semi-analytical solution for simulating contaminant transport subject to chain
decay reactions.
AB - We present a set of new, semi-analytical solutions to simulate three-dimensional
contaminant transport subject to first-order chain-decay reactions. The aquifer
is assumed to be areally semi-infinite, but finite in thickness. The analytical
solution can treat the transformation of contaminants into daughter products,
leading to decay chains consisting of multiple contaminant species and various
reaction pathways. The solution in its current form is capable of accounting for
up to seven species and four decay levels. The complex pathways are represented
by means of first-order decay and production terms, while branching ratios
account for decay stoichiometry. Besides advection, dispersion, bio-chemical or
radioactive decay and daughter product formation, the model also accounts for
sorption of contaminants on the aquifer solid phase with each species having a
different retardation factor. First-type contaminant boundary conditions are
utilized at the source (x=0 m) and can be either constant-in-time for each
species, or the concentration can be allowed to undergo first-order decay. The
solutions are obtained by exponential Fourier, Fourier cosine and Laplace
transforms. Limiting forms of the solutions can be obtained in closed form, but
we evaluate the general solutions by numerically inverting the analytical
solutions in exponential Fourier and Laplace transform spaces. Various cases are
generated and the solutions are verified against the HydroGeoSphere numerical
model.
PMID- 23153685
TI - [Somatoform disorders in neurology visits: history and circumstances:
retrospective study of 124 cases].
AB - We report 124 cases of somatoform disorders, considering psychogenic disorders at
the same level as neurological disorders. We noted any psychic, somatic or social
condition (history taking) and facilitating circumstances. The patients were aged
16 to 84 years old; 71.7% were women. We observed pain (35.4%), psychogenic
headache (25%), sensorimotor loss (27.4%), gait and psychogenic tremor (17.7%),
cognitive disorders (11.8%), ocular symptoms (7.2%), and urogenital symptoms
(2.4%). Delay to consultation ranged from a few days to 20 years. Psychiatric
comorbidity was noted in 30.6% of the cases. In 55.6% of 124 cases, we observed a
psychological background. It was a childhood trauma in 15.3% of these cases. In
one-third of the 124 situations, we noted an underlying somatic or social
condition. Facilitation conditions were frequently mixed. Somatic and/or
psychological conditions were noted in one-third of the 124 cases and social
conditions in half of them. The neurologist is faced with the challenge of naming
the symptom (most often labelled a functional disorder) and of making the
decision to stop or limit investigations. Visits by patients with psychogenic
disorders make up a significant percentage of neurology speciality appointments.
The neurologist should not limit the consultation to differentiating "real"
symptoms from psychogenic somatoform disorders, but should also propose a
straightforward compassionate approach for effective therapeutic care. By
carefully listening to the patient's dialogue, the neurologist can help the
patient give meaning to the symptoms, and progress towards improved well-being.
PMID- 23153686
TI - [Developments in hereditary neuropathies].
AB - Hereditary sensorimotor neuropathies, or Charcot-Marie-Tooth disease (CMT)
comprise a group of diseases with heterogeneous clinical, electrophysiological
and genetic expression. They are classified by the mode of inheritance (autosomal
dominant, X-linked dominant, autosomal recessive) and their electrophysiological
characteristics taking into account the speed of motor conduction of the median
nerve (demyelinating, intermediary and axonal forms). Certain purely motor forms
are called spinal CMT or hereditary distal motor neuropathy, or distal spinal
amyotrophy. CMT involving an important sensorial component, trophic disorders, or
signs of dysautonomia are included in the classification of hereditary sensory
and autonomic neuropathies.
PMID- 23153688
TI - Hypertension caused by primary hyperaldosteronism: increased heart damage and
cardiovascular risk.
AB - INTRODUCTION AND OBJECTIVES: Primary hyperaldosteronism is the most common cause
of secondary hypertension. Elevated aldosterone levels cause heart damage and
increase cardiovascular morbidity and mortality. Early diagnosis could change the
course of this entity. The objective of this report was to study the clinical
characteristics, cardiac damage and cardiovascular risk associated with primary
hyperaldosteronism. METHODS: We studied 157 patients with this diagnosis. We
analyzed the reason for etiological investigation, and the routinely performed
tests, including echocardiography. We used a cohort of 720 essential hypertensive
patients followed in our unit for comparison. RESULTS: Compared with essential
hypertensive patients, those with hyperaldosteronism were younger (56.9 [11.7]
years vs 60 [14.4] years; P<.001), had higher blood pressure prior to the
etiological diagnosis (136 [20.6] mmHg vs 156 [23.2] mmHg), more frequently had a
family history of early cardiovascular disease (25.5% vs 2.2%; P<.001), and had a
higher prevalence of concentric left ventricular hypertrophy (69% vs 25.7%) and
higher cardiovascular risk. Specific treatment resulted in optimal control of
systolic and diastolic blood pressures (from 150.7 [23.0] mmHg and 86.15 [14.07]
mmHg to 12.69 [15.3] mmHg and 76.34 [9.7] mmHg, respectively). We suspected the
presence of hyperaldosteronism because of resistant hypertension (33.1%),
hypokalemia (38.2%), and hypertensive crises (12.7%). Only 4.6% of these patients
had been referred from primary care with a suspected diagnosis of
hyperaldosteronism. CONCLUSIONS: Hyperaldosteronism should be suspected in cases
of resistant hypertension, hypokalemia and hypertensive crises. The diagnosis of
hyperaldosteronism allows better blood pressure control. The most prevalent
target organ damage is left ventricular hypertrophy.
PMID- 23153689
TI - Computer-aided detection/diagnosis of breast cancer in mammography and
ultrasound: a review.
AB - Breast cancer is the most common form of cancer among women worldwide. Early
detection of breast cancer can increase treatment options and patients'
survivability. Mammography is the gold standard for breast imaging and cancer
detection. However, due to some limitations of this modality such as low
sensitivity especially in dense breasts, other modalities like ultrasound and
magnetic resonance imaging are often suggested to achieve additional information.
Recently, computer-aided detection or diagnosis (CAD) systems have been developed
to help radiologists in order to increase diagnosis accuracy. Generally, a CAD
system consists of four stages: (a) preprocessing, (b) segmentation of regions of
interest, (c) feature extraction and selection, and finally (d) classification.
This paper presents the approaches which are applied to develop CAD systems on
mammography and ultrasound images. The performance evaluation metrics of CAD
systems are also reviewed.
PMID- 23153690
TI - Reactivity of iron(II)-bound nitrosyl hydride (HNO, nitroxyl) in aqueous
solution.
AB - The reactivity of coordinated nitroxyl (HNO) has been explored with the
[Fe(II)(CN)(5)HNO](3-) complex in aqueous medium, pH 6. We discuss essential
biorelevant issues as the thermal and photochemical decompositions, the
reactivity toward HNO dissociation, the electrochemical behavior, and the
reactions with oxidizing and reducing agents. The spontaneous decomposition in
the absence of light yielded a two-electron oxidized species, the nitroprusside
anion, [Fe(II)(CN)(5)NO](2-), and a negligible quantity of N(2)O, with
k(obs)~5*10(-7)s(-1), at 25.0 degrees C. The value of k(obs) represents an upper
limit for HNO release, comparable to values reported for other structurally
related L ligands in the [Fe(II)(CN)(5)L](n-) series. These results reveal that
the FeN bond is strong, suggesting a significant sigma-pi interaction, as already
postulated for other HNO-complexes. The [Fe(II)(CN)(5)HNO](3-) ion showed a quasi
reversible oxidation wave at 0.32 V (vs normal hydrogen electrode), corresponding
to the [Fe(II)(CN)(5)HNO](3-)/[Fe(II)(CN)(5)NO](3-),H(+) redox couple.
Hexacyanoferrate(III), methylviologen and the nitroprusside ion have been
selected as potential oxidants. Only the first reactant achieved a complete
oxidation process, initiated by a proton-coupled electron transfer reaction at
the HNO ligand, with nitroprusside as a final oxidation product. Dithionite acted
as a reductant of [Fe(II)(CN)(5)HNO](3-), in a 4-electron process, giving NH(3).
The high stability of bound HNO may resemble the properties in related Fe(II)
centers of redox active enzymes. The very minor release of N(2)O shows that the
redox conversions may evolve without disruption of the FeN bonds, under
competitive conditions with the dissociation of HNO.
PMID- 23153691
TI - A new set of risk equations for predicting long term risk of all-cause mortality
using cardiovascular risk factors.
AB - OBJECTIVES: As population ages and treatment for cardiovascular disease improves
the risk of all-cause mortality has become a more meaningful outcome. We develop
all-cause mortality equations for predicting long term risk using cardiovascular
risk factors. METHODS: The 24-year risk of all-cause mortality was evaluated
using Cox model for participants aged 40-81 years at the 10th or 11th examination
of the Framingham original cohort and the first examination of the offspring
cohort-all of whom were free of major chronic diseases. RESULTS: The predictors
of all-cause mortality were age, sex, systolic blood pressure, total
cholesterol/HDL ratio and smoking status. Risk prediction improved significantly
when intensity of smoking and time since quitting were included into smoking
status. A reduced model based on non-laboratory risk factors also demonstrated
good predictive performance. CONCLUSIONS: All-cause mortality risk equations
incorporating cardiovascular risk factors provide an improved tool to quantify
risk and guide prevention of mortality. There are great potentials for prevention
of the CVD epidemic and for increased longevity with health, through improved
life-styles and consequent lower levels of blood pressure, cholesterol and
smoking.
PMID- 23153692
TI - Short-term hypoxia increases phosphorylated tyrosine hydroxylase at Ser31 and
Ser40 in rat carotid body.
AB - Long-term hypoxia (days to weeks) increases phosphorylation of tyrosine
hydroxylase (TH) at Ser31 and Ser40 in the carotid body (CB). In the present
study, we examined the time course of TH phosphorylation at Ser31 and Ser40 in CB
of rats exposed to short-term hypoxia (within 1 day) for 0-24 h. Using
immunoblotting, the signal intensities of both phosphorylated TH were more
intense in CB of rats exposed to hypoxia for 6, 12, 18, and 24h than those of
controls. Using immunohistochemistry, immunoreactive intensities of both
phosphorylated TH were significantly more intense in glomus cells after rats were
exposed to hypoxia for 6, 12, 18, and 24 h than those of controls (p<0.05). These
results show that phosphorylation of TH at Ser31 and Ser40 is increased in CB
glomus cells by short-term hypoxia, suggesting that activation of TH via
phosphorylation contributes to the facilitation of catecholamine biosynthesis in
CB glomus cells at an early stage of hypoxia.
PMID- 23153693
TI - Effect of progesterone on respiratory response to moderate hypoxia and apnea
frequency in developing rats.
AB - We used whole-body plethysmography and pulse oximetry to assess the effects of
acute administration of progesterone (4 mg/kg, i.p.) on normoxic ventilation,
hypoxic ventilatory response (HVR: FiO(2)=12% over 20 min), metabolism, and apnea
frequency in rats on postnatal (P) days P1, P4, P7, and P12. Arterial oxygen
saturation was continuously measured, and apneas were discriminated based on the
degree of associated desaturation, at least 5 units less than the value before
the desaturation. In normoxia, progesterone did not alter ventilation, metabolism
or the coefficient of variation of minute ventilation at any age studied when
compared with the control group (saline). However, it decreased apnea frequency
and apnea associated with desaturation only in P1 rats. In hypoxia: progesterone
increased the peak HVR in P4 and P7 rats, increased the steady-state HVR (mean at
15-20 min of exposure) in P1, P4 and P7 without affecting the rats' metabolic
rate, decreased the coefficient of variation of minute ventilation in P4 and P7
rats, and finally, decreased apnea frequency only in the P1 rats with no effect
on apnea associated with desaturation at any age. We conclude that acute
administration of progesterone has no effect on baseline ventilation, but it
increases HVR in rats younger than 7 days, and decreased the frequency of apnea
only in P1 rats.
PMID- 23153694
TI - Outgoing editor-in chief.
PMID- 23153695
TI - Oviparity or viviparity? That is the question....
AB - The modes of reproduction undoubtedly represent one of the most critical life
history traits because they profoundly affect fitness and survival. The parent
offspring conflict over the degree of parental investment may be the main
selective factor in the evolution of reproduction. Although the modes of sexual
reproduction are remarkably diversified in animals, the traditional typology
spanning three classes does not seem to be adequate to clarify the level of
parental investment. Thus, lecithotrophy does not provide any information on the
retention of the zygotes inside the parent's body and matrotrophy only indicates
that nutrients are provided by mother but does not make any distinction between
various types of maternal care. I here present a scientific typology of the
reproductive modes comprising five classes: ovuliparity, oviparity, ovo
viviparity, histotrophic viviparity and hemotrophic viviparity. Based on the
development stage of the zygote and on its interrelation with the parent, my
classification details the degree of contrivances by which animals provide
alternative parental investment in their offspring. Hence, this typology
possesses a great heuristic value, both in reproduction and evolutionary biology.
These different modes of reproduction do represent a sequence, with ovuliparity
being the most primitive and hemotrophic viviparity the most advanced mode.
Lastly, the comparative analysis of different reproductive modes in vertebrates
suggests that climatic conditions (cold) could be one of the strongest selection
pressures for extending egg retention and the establishment of viviparity.
PMID- 23153696
TI - Advances in understanding the physiological mechanism of maternal immune
tolerance to the embryo.
AB - The results of immunological studies, especially research conducted in the last
decade, have shown that free (not bound to protein) progesterone molecules
(fP(4)) can block the ability of dendritic cells, monocytes and macrophages to
present antigens to Th cells and thereby reduce maternal immune activity and
increase the maternal tolerance to the semiallogenic embryo. Endocrine studies
have shown that fP(4) in the female reproductive organs are transferred at high
concentrations into the arterial blood that supplies the oviduct and uterus due
to the special adaptations of the blood circulation and lymph flow. Here, the
authors present the results of numerous studies documenting their thesis that an
important element of maternal tolerance of the semiallogenic embryo in the uterus
is conditioned by the close interaction of two processes that occur in the
reproductive organs: (1) the local decrease of maternal immune system activity,
in which the ability of dendritic cells, macrophages and monocytes to present
embryonic antigens to Th cells is blocked by fP(4); and (2) the proper function
of the system governing the local retrograde and destination transfer of
hormones, which increases the concentration of fP(4) that are able to immediately
bind to their receptors in dendritic cells and in the monocytes and macrophages
present in the blood supplying the oviduct and uterus. The authors believe that
the local interaction of the immune and endocrine systems in the female
reproductive tract reduces local maternal immunoreactivity and thus fulfils a
critical physiological role; this mechanism protects the embryo but does not
change the general immunological resistance of the mother.
PMID- 23153697
TI - Glutathione-supplemented tris-citric acid extender improves the post-thaw quality
and in vivo fertility of buffalo (Bubalus bubalis) bull spermatozoa.
AB - In this study we evaluated the effects of semen extender supplementation with
different concentrations of glutathione (GSH) on buffalo (Bubalus bubalis) bull
sperm motility, plasma membrane integrity, viability and DNA integrity as well as
in vivo fertility. Semen from three Nili-Ravi buffalo bulls was collected, and
qualified semen ejaculates (n=18) were split into five aliquots for dilution (37
degrees C; 50*10(6)spermatozoaml(-1)) with experimental tris-citric acid extender
containing 0, 0.5, 1.0, 1.5 or 2.0 mM GSH. Extended semen was cooled to 4 degrees
C, equilibrated and filled in French straws. The straws were kept on liquid
nitrogen vapors (5 cm above the LN(2) level) for 10 min and plunged in liquid
nitrogen for storage. Sperm motility (%), plasma membrane integrity (%),
viability (%) and DNA integrity (%) were assessed at 0, 2 and 4h post-thawing (37
degrees C). Extender supplementation with GSH (0.5, 1.0, 1.5 and 2.0 mM)
increased sperm motility, plasma membrane integrity and viability in a dose
dependent manner. Sperm DNA integrity was higher (p<0.05) in all experimental
extenders containing GSH when compared to the control extender (0 mM GSH). The in
vivo fertility rate of cryopreserved buffalo bull (n=2) spermatozoa was higher
(p<0.05) in extender containing 2.0 mM GSH compared to that of control. In
summary, tris-citric acid extender supplemented with glutathione improved the
freezability of buffalo bull spermatozoa in a dose dependant manner. Moreover,
the addition of 2.0 mM GSH to the extender enhanced the in vivo fertility of
buffalo (Bubalus bubalis) bull spermatozoa.
PMID- 23153698
TI - The effect of radio electric asymmetric conveyer treatment on sperm parameters of
subfertile stallions: a pilot study.
AB - The Radio Electric Asymmetric Conveyer (REAC) has been mostly applied to treat
symptoms related to psychological stress. In the study, we demonstrated the
effect of REAC-Veterinary Neuro Psycho Physical Optimization (VNPPO) treatment
protocol on sperm parameters of subfertile (n=11) and fertile (n=4) stallions.
Subfertile stallions showed a reduced sperm concentration, progressive motility
and normal morphology compared to fertile stallions. An increase in progressive
sperm motility and quality of sperm morphology was found in subfertile stallions
after the REAC-VNPPO treatment. The positive effect of the REAC-VNPPO treatment
was visible in a reduced number of reacted or absent acrosomes, nuclei with
marginated chromatin and presence of cytoplasmic residues. Thus, we suggest that
the REAC-VNPPO treatment for stallions with idiopathic subfertility may enhance
the reproductive performance of stallions.
PMID- 23153699
TI - Effects of quinestrol and levonorgestrel on prolactin serum concentration in
lactating Mongolian gerbils (Meriones unguiculatus) and reproductive parameters
of their offspring.
AB - The effects of the two sterilants, quinestrol (QE) and levonorgestrel (LNG) on
serum prolactin (PRL) level in lactating Mongolian gerbils and reproductive
parameters of their offspring were examined in the study. Both sterilants
increased the serum PRL level in lactating gerbils. The body weight as well as
weights of the ovary, testis, epididymides, and seminal vesicles were lower,
whereas that of the uterus was higher in the pups originating from QE-treated
mothers in comparison to controls. Histological ovarian sections of the offspring
from QE-treated mothers contained only growing follicles, whereas their uterine
sections showed a thinner endometrium, thicker myometrium, and greater epithelial
cell height than in controls. The histometrical testis characteristics as well as
sperm concentration and motility of male pups from QE-treated mothers were lower
compared to those of the control group. The serum gonadotropin levels of female
pups from mothers treated with QE were lower, whereas the serum estradiol (E(2))
and progesterone (P(4)) levels were higher than in control gerbils. In contrast,
serum gonadotropin and testosterone (T) levels of male pups from QE-treated
mothers were lower compared to controls. LNG did not affect the examined
parameters of the offspring. The offspring from QE-treated mothers was infertile,
whereas the offspring from LNG-treated mothers was fertile. In summary, QE and
LNG have a stimulatory effect on PRL level in lactating gerbils. It also appears
that QE administered via milk to mothers affects reproductive processes of their
offspring.
PMID- 23153700
TI - Expression of ghrelin receptor (GHSR-1a) in rat epididymal spermatozoa and the
effects of its activation.
AB - In this study we demonstrated the expression of the ghrelin receptor GHSR-1a in
rat spermatids and epididymal spermatozoa, as well as some effects of ghrelin on
the spermatozoa in vitro. For the demonstration of GHSR-1a the
immunocytochemical, immunofluorescence and Western blotting techniques were
applied using three different types of antibodies. The response of spermatozoa to
ghrelin was tested in a series of in vitro experiments and their effects were
evaluated using confocal microscopy and flow cytometry. GHSR-1a protein was found
as expressed in the Golgi and acrosomes of spermatids and acrosome regions or the
head cell membrane of epididymal spermatozoa. The GHSR-1a expression in
spermatozoa was also confirmed by Western blot. No differences were found in
percentage of spermatozoa showing annexin-V binding and expression of active form
caspase-3 between control and ghrelin-treated spermatozoa. This result may
indicate no pro-apoptotic effects of ghrelin neither at 10(-9) nor 10(-6)mol/L
concentration. Ghrelin (10(-6)mol/L) increased free intracellular calcium ion
concentration in the rat spermatozoa. Moreover, stimulation with 10(-6)mol/L
ghrelin increased, while 10(-4)mol/L ghrelin decreased the number of spermatozoa
showing progressive motility. In conclusion, the expression of the GHSR-1a
receptor in spermatozoa, as well as ghrelin influences on sperm motility and
intracellular calcium ion concentration suggest that such biological effects of
ghrelin may be produced under in vivo conditions.
PMID- 23153701
TI - Testosterone, gonadotropins and androgen receptor during spermatogenesis of
Biomphalaria alexandrina snails (Pulmonata: Basommatophora).
AB - Endocrine regulation of reproductive processes of the snail Biomphalaria
alexandrina is poorly recognized. Thus, the aims of the study were: (1) to
acquire histological images of the ovotestis; (2) to determine the hemolymph
concentrations of testosterone (T) and gonadotropic hormones (luteinizing
hormone: LH and follicle stimulating hormone: FSH), (3) to demonstrate androgen
receptor (AR) immunolocalization in the ovotestis, and (4) to show LH and FSH
protein expression in cerebral ganglia of small (diameter shell: 4-6mm), medium
(7-11mm) and large (12-16mm) B. alexandrina snails. These three groups
represented different reproductive stages of the snail. The AR immunoexpression
was found in the periphery and inside the acini of small (immature) snails as
well as in spermatocytes, spermatids, Sertoli cells, the interstitial cells and
the acinus lining epithelium of medium (mature) snails. Low AR immunoexpression
was demonstrated in the interstitial cells of large (aged) snails. The neurons at
the periphery of the cerebral ganglia and connective sheath of the ganglia showed
a positive FSH and LH immunostaining. T concentration in the hemolymph was higher
in medium snails than in small and large snails. In contrast, LH concentration
was higher in medium snails than in small and large snails. These data suggests
that gonadotropins and T play a role in the gonadal development in B.
alexandrina.
PMID- 23153702
TI - Caprine endometrial stromal cells modulate the effects of steroid hormones on
cytokine secretion by endometrial epithelial cells in vitro.
AB - The main purpose of this study was to examine the effects of 17beta-estradiol
(E(2)) and progesterone (P(4)) on cytokine secretion by caprine endometrial
epithelial cells (EEC) in vitro. Epithelial cells grown alone or in co-culture
with stromal cells (ESC) were treated with E(2) or P(4), or both. Homogeneity of
the endometrial cell populations was ascertained immunocytochemically. The
quantities of cytokines secreted in this system were assessed by ELISA and their
protein expression by Western blot. The exposure of EEC to P(4) alone or in
combination with E(2) significantly increased the amount of TGF-beta1, TNF-alpha
and IL-18 secretion, whereas E(2) had no effect on the synthesis of these
cytokines. When epithelial cells were co-cultured with ESC, the secretion of TGF
beta1, TNF-alpha and IL-18 by EEC significantly increased compared to that by EEC
alone. However, the treatment with both steroids decreased the secretion of TNF
alpha, IL-18 and TGF-beta1 by EEC in the presence of ESC. In contrast to TGF
beta1, TNF-alpha and IL-18, the secretion of leukemia inhibitory factor (LIF) by
EEC was not affected by E(2) and/or P(4) either directly or indirectly. The
present results indicate that the interactions between caprine endometrial
stromal and epithelial cells can modulate the secretion of TGF-beta1, TNF-alpha
and IL-18 by EEC exposed to E(2) and/or P(4)in vitro.
PMID- 23153703
TI - Direct in vitro effect of LH and steroids on leptin gene expression and leptin
secretion by porcine luteal cells during the mid-luteal phase of the estrous
cycle.
AB - Leptin, the product of the ob gene, is implicated in the control of reproductive
functions in different species. Leptin transcript and protein are present in
several tissues including adipose tissue and corpus luteum. The regulation of
leptin mRNA expression and leptin secretion in porcine luteal cells is not clear.
In this study, we determined leptin and OB-Rb mRNA/protein levels in porcine
luteal cells during the mid-luteal phase of the estrous cycle (days 10-12) and
examined, in vitro, the effects of LH, 17-beta estradiol (E(2)) and progesterone
(P(4)) on leptin gene expression and leptin secretion in those cells. Leptin and
long form of leptin receptor (OB-Rb) mRNA expressions as well as leptin and OB-Rb
protein were detected in the luteal cells by real-time PCR and fluorescence
immunocytochemistry (F-ICC), respectively. Isolated luteal cells, after
preliminary culture (48 h) were treated with LH (1; 10; 100 ng/ml), E(2) (0.02;
0.2; 2; 20 ng/ml) and P(4) (20; 100; 200 ng/ml) for 24 h. LH did not induce
significant changes in leptin mRNA expression in the luteal cells. A higher level
of leptin transcript was found in the presence of E(2) (0.02 ng/ml) or P(4) (200
ng/ml). Estradiol (0.2 ng/ml) and P(4) (200 ng/ml) increased leptin secretion by
luteal cells. Our results indicate that leptin and OB-Rb genes and proteins are
expressed in porcine luteal cells and suggest that steroid hormones (E(2) and
P(4)) affect leptin mRNA expression and leptin secretion during the mid-luteal
phase of the estrous cycle.
PMID- 23153704
TI - Comparison of the patterns of antral follicular development between hormonally
synchronized and natural estrous cycles of non-seasonal, polyestrous goats in the
tropics.
AB - The effects of estrus synchronization with prostaglandin F(2alpha) (PGF(2alpha))
and Controlled Internal Drug Release Device (CIDR) on ensuing antral follicular
development were documented and compared to natural estrous cycles of non
seasonal tropical goats. Two to six follicular waves were observed, with the
three-follicular wave pattern being most frequently observed (58%), followed by
four follicular waves (31.6%) per estrous cycle. There were no significant
differences (p>0.05) between the PGF(2alpha)- or CIDR-synchronized and natural
estrous cycles nor between the synchronized and subsequent non-synchronized
cycles in terms of the time of ovulation, the duration of inter-ovulatory
intervals, daily numbers of antral follicles >=3mm in diameter, and the number of
follicular waves per cycle in the goats of the present study.
PMID- 23153705
TI - A preliminary search for alternatives to albumin as a medium supplement for the
culture of human sperm.
AB - Non-animal macromolecules (Select PhytoneTM UF, wheat peptone, dextran 40,
hydroxyethyl starch and methyl cellulose) as an alternative medium supplement for
human spermatozoa were compared to bovine serum albumin. Select PhytoneTM UF and
wheat peptone discolored the medium and smelled like broth, making them unlikely
to be acceptable for clinical use, whilst the others were colorless and odorless.
All supplements were effective in the yield of spermatozoa isolated by swim-up
technique, and maintenance of sperm motility. In summary, there are non-animal
macromolecules that will support short-term sperm culture.
PMID- 23153706
TI - Targeting epidermal growth factor receptor/human epidermal growth factor receptor
2 signalling pathway by a dual receptor tyrosine kinase inhibitor afatinib for
radiosensitisation in murine bladder carcinoma.
AB - Given the promising control of bladder cancer achieved by combined
chemotherapy/radiotherapy with selective transurethral resection, obstacles
remain to the treatment of unresectable bladder cancer. The aim of this study was
to determine whether targeting epidermal growth factor receptor (EGFR)/human
epidermal growth factor receptor 2 (HER2) can radiosensitise a murine bladder
tumour (MBT-2) cell line. Cell survival, expression of signal proteins and cell
cycle changes in MBT-2 cells treated in vitro and in vivo with afatinib, an
irreversible EGFR/HER2 inhibitor, plus radiotherapy were investigated by colony
formation assay, Western blot assay and flow cytometry, respectively. Ectopic
xenografts were established by subcutaneous injection of MBT-2 cells in C3H/HeN
mice. Mice were randomised into 4 groups to receive afatinib (10mg/kg/day on day
1-7) and/or radiotherapy (15Gy on day 4). Positron emission tomography (PET) on
day 8 was used to evaluate the early treatment response. Afatinib (200-1000nM)
increased cell killing by radiation (0-10Gy). Pre-treatment of irradiated cells
with afatinib inhibited radiation-activated HER2 and EGFR phosphorylation. As
compared to either treatment alone, the combination increased the level of the
cleavage form of poly (ADP-ribose) polymerase, the expression of phospho
gammaH2AX and the percentage of cells in subG1 phase (indicating enhanced
induction of apoptosis), and decreased tumour metabolism and inhibited tumour
growth by 64%. Afatinib has therapeutic value as a radiosensitiser of murine
bladder cancer cells. The synergism between afatinib and radiation likely
enhances DNA damage, leading to increased cell apoptosis.
PMID- 23153707
TI - The association between perinatal testosterone concentration and early vocabulary
development: a prospective cohort study.
AB - Prenatal exposure to testosterone is known to affect fetal brain maturation and
later neurocognitive function. However, research on the effects of prenatal
testosterone exposure has been limited by indirect measures of testosterone and
small unrepresentative samples. This study investigated whether bioavailable
testosterone (BioT) concentrations in umbilical cord blood are associated with
expressive vocabulary development, in a large birth cohort. Cord blood samples
were taken immediately after delivery and expressive vocabulary was measured at
two years of age using the language development survey (LDS). BioT concentration
significantly predicted vocabulary size in males (n=197), such that higher
concentrations were associated with lower LDS scores, indicating smaller
vocabulary. This relationship between BioT concentrations and vocabulary at aged
2 years was not observed in girls (n=176). Higher circulating prenatal
testosterone concentrations at birth may be associated with reduced vocabulary in
early childhood among boys.
PMID- 23153708
TI - Brain-computer interface and semantic classical conditioning of communication in
paralysis.
AB - We propose a classical semantic conditioning procedure to allow basic yes-no
communication in the completely locked-in state as an alternative to instrumental
operant learning of brain responses, which is the common approach in brain
computer interface research. More precisely, it was intended to establish
cortical responses to the trueness of a statement irrespective of the particular
constituent words and letters or sounds of the words. As unconditioned stimulus
short aversive stimuli consisting of 1-ms electrical pulses were used. True and
false statements were presented acoustically and only the true statements were
immediately followed by electrical stimuli. 15 healthy participants and one
locked-in ALS patient underwent the experiment. Three different classifiers were
employed in order to differentiate between the two cortical responses by means of
electroencephalographic recordings. The offline analysis revealed that semantic
classical conditioning can be applied successfully to enable basic communication
using a non-muscular channel.
PMID- 23153709
TI - Antituberculosis drug-induced hypersensitivity syndrome and its association with
human leukocyte antigen.
AB - Antituberculosis drug (ATD)-induced hypersensitivity syndrome (HSS) is a serious
adverse reaction to ATDs, but much remains to be determined regarding its
characteristics and genetic risk factors. In this study, we have collected cases
of ATD-induced HSS and their clinical features, and investigated the associations
of ATD-induced HSS with human leukocyte antigen (HLA). Subjects with ATD-induced
HSS and ATD-tolerant controls were recruited through analysis of a multicenter
adverse drug reaction registry in Korea. HLA allele frequencies were compared
between subjects with ATD-induced HSS (n = 14) and two control groups: ATD
tolerant controls (n = 166) and the general population (n = 485). The number of
enrolled subjects with ATD-induced HSS (n = 14) was comparable to those of
patients with HSS induced by other common drugs such as allopurinol during the
recruitment period. The frequency of Cw*0401 was much higher in the cases (50.0%)
compared with ATD-tolerant controls (12.7%, Pc = 0.0204, OR = 6.90) and the
general population (12.8%, Pc = 0.0132, OR = 6.82). Our results suggest that ATD
is an important causative agent inducing HSS with distinct clinical features. The
strong association of Cw*0401 with the risk for ATD-induced HSS suggests
immunological involvement in the development of this syndrome.
PMID- 23153710
TI - Olfactory function in patients with and without temporal lobe resection.
AB - OBJECTIVES: The study aimed to assess olfactory function in patients with
temporal lobe epilepsy before and after resection of temporal lobe structures and
especially addressed the question whether there are any significant olfactory
differences as a function of side of epileptic focus or resection. MATERIALS AND
METHODS: Thirteen pre- and 22 postoperative patients and 35 age- and sex-matched
healthy controls underwent olfactory testing by means of the Sniffin' Sticks
testing device (comprehensive measurement of threshold, discrimination, and
identification abilities). RESULTS: Patients with unilateral epileptic focus but
without temporal lobe resection tended to have impaired identification abilities
only compared to the healthy controls. There were no significant differences in
olfactory function on the side of the epileptic focus compared to the non
affected side. However, the patients after temporal lobe resection presented with
significantly impaired bilateral discrimination and identification abilities
compared to the healthy controls and with lower olfactory scores on the side of
the lesion compared to the non-lesioned side. CONCLUSIONS: Olfactory function is
only partially impaired preoperatively and will deteriorate further after the
partial resection on the side of the lesion.
PMID- 23153711
TI - Validation of a German version of the Neurological Disorders Depression Inventory
for Epilepsy (NDDI-E).
AB - INTRODUCTION: Goal of the present study was the validation of a German version of
the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E). METHODS:
197 adult epilepsy patients completed the NDDI-E (185 completed both the NDDI-E
and BDI). 95 patients received psychiatric consults. RESULTS: 33 patients
received a diagnosis of major depression according to ICD-10 criteria. Internal
consistency of the NDDI-E was .83. Receiver operating characteristics (ROC)
showed an area under the curve of 0.92. Applying a cutoff score of >=14 resulted
in both sensitivity and specificity of 0.85. In the subsample with psychiatric
consult, at the same optimal cutoff, sensitivity was 0.92, and specificity was
0.86. Further analyses showed a high concurrent validity with the BDI.
DISCUSSION: The German version of the NDDI-E constitutes a brief and reliable
depression screening instrument for epilepsy patients.
PMID- 23153712
TI - Employment in people with epilepsy from the perspectives of patients,
neurologists, and the general population.
AB - OBJECTIVE: Finding and continuing employment are among the most important issues
for patients with epilepsy (PWE). Earlier studies indicated overrepresentation of
PWE in manual unskilled or semiskilled positions. METHODS: The questionnaire
based study was carried out throughout Poland between February and March 2009.
995 PWE (18-65 yrs), 179 neurologists, and a representative sample of the Polish
population over 15 yrs of age (1042) were included. RESULTS: 49% of PWE were
employed. Patients with epilepsy most commonly work as service and sales workers,
office workers, professionals, and technicians. 56% of Poles, 25% of patients,
and 28% of neurologists believed that all PWE could work. CONCLUSIONS: Almost 3/4
of PWE held non-manual positions. This contradicts the stereotype of unskilled
professions being more suitable for PWE. Generally, Poles have a positive
attitude towards employment of PWE, but the lack of knowledge about the condition
makes them less prudent than neurologists and the PWE themselves.
PMID- 23153713
TI - Early screening and identification of psychological comorbidities in pediatric
epilepsy is necessary.
AB - Youth with epilepsy often have co-occurring psychological symptoms that are due
to underlying brain pathology, seizures, and/or antiepileptic drug side effects.
The primary study aim was to compare the psychological comorbidities of youth
with new-onset epilepsy versus chronic epilepsy. Primary caregivers of youth with
either new-onset (n=82; M(age)=9.9+/-2.9) or chronic epilepsy (n=76;
M(age)=12.8+/-3.3) completed the Behavioral Assessment Scale for Children-2nd
Edition. Compared to those with new-onset epilepsy, the chronic group had
significantly higher depressive and withdrawal symptoms, as well as lower
activities of daily living. A higher proportion of youth with chronic epilepsy
exhibited at-risk/clinically elevated depressive symptoms and difficulties with
activities of daily living compared to the new-onset group. Proactive screening
in youth with epilepsy to ensure timely identification of psychological symptoms
and to guide early psychological intervention is warranted.
PMID- 23153715
TI - Behavioral intervention as an add-on therapy in epilepsy: designing a clinical
trial.
AB - Many patients with epilepsy continue to experience seizures despite taking
medication, and stress is a commonly reported trigger for seizures in these
individuals. Therefore, a behavioral therapy proven to be effective in epilepsy
could be a valuable adjunct to current pharmacotherapy. The challenges in testing
such a behavioral intervention for epilepsy are numerous, including lack of
consensus about sham designs, maintaining the blind, and powering the study
absent known effect sizes. Herein, we present the design of a randomized,
controlled, double-blind trial of progressive muscle relaxation as an add-on
therapy for refractory epilepsy. Progressive muscle relaxation, which involves
the tensing and releasing of muscle groups one at a time, is a well-established
technique that relaxes the body and mind, reduces stress, and may improve seizure
control. Study design issues discussed may provide insights that will inform
future behavioral research in epilepsy.
PMID- 23153714
TI - Ictal dystonia and secondary generalization in temporal lobe seizures: a video
EEG study.
AB - The aim of this study was to determine whether the occurrence of unilateral ictal
limb dystonia (ID) during complex partial seizures (CPS) reduces the possibility
of contralateral propagation (CP) and secondary generalization (SG) in patients
with temporal lobe epilepsy (TLE). We assessed 216 seizures recorded in 33
patients with pharmacoresistant TLE. All patients underwent video-EEG telemetry
prior to surgical treatment with good postoperative outcomes (Engel I). Ictal
limb dystonia was observed in 16 of the 33 patients (48%) and 58 of the 216
seizures (26.8%). We found highly significant differences in the frequency of SG
between seizures with ID and seizures without ID (2/58 vs. 41/158; 3.45% vs.
25.95%; p<0.001). Contralateral propagation was seen in 13 of the 57 analyzed
seizures with ID compared to 85 of the 158 seizures without ID (22.8% vs. 53.8%;
p<0.001). Among the CPS without SG, we found that the mean duration of seizures
with ID was significantly longer than the duration of seizures without ID
(81.66+/-40.10 vs. 68.88+/-25.01 s; p=0.011). Our findings that CP and SG occur
less often in patients with ID, yet the duration of CPS without SG is longer in
patients with ID, suggest that the basal ganglia might inhibit propagation to the
contralateral hemisphere but not ictal activity within the unilateral epileptic
network.
PMID- 23153716
TI - The antidepressant sertraline prevents the behavioral and EEG changes induced in
two animal models of seizures.
AB - In order to investigate a potential anticonvulsive action of sertraline (i.p.),
its effects on seizures, EEG epileptiform activity and EEG amplitude increases
induced by two convulsive agents were evaluated and compared with the effects of
carbamazepine. Around 20 min following 4-aminopyridine (4-AP, 2.5 mg/kg, i.p.),
tonic-clonic seizures and epileptiform activity were observed in control animals.
A single sertraline pre-injection of 2.5 mg/kg, but not of 0.75 mg/kg, prevented
these changes to 4-AP. Repeated daily administration of 0.75 mg/kg for one week,
however, effectively inhibited the changes induced by 4-AP. The first generalized
tonic-clonic seizure and EEG changes in response to pentylenetetrazole (PTZ, 50
mg/kg, i.p.) were observed near the first minute in control animals. Single
sertraline doses above 5 mg/kg prevented the PTZ-induced changes. Moreover, a
single carbamazepine dose of 25 mg/kg (i.p.), but not of 15 mg/kg, prevented the
changes induced by the above convulsive agents. An anti-seizure action of the
antidepressant sertraline is strongly suggested by these findings.
PMID- 23153717
TI - Biperiden for treatment of somnambulism in adolescents and adults with or without
epilepsy: clinical observations.
AB - BACKGROUND: Sleepwalking in adolescents and adults may lead to serious injuries
and require treatment. Anecdotal treatment recommendations include
benzodiazepines (which also work in focal seizures of the frontal lobe that are
an important differential diagnosis), imipramine and amitriptyline. METHODS: We
assessed in a follow-up study of 4 years (medium, range: 2-7 years) the
usefulness of the antiparkinsonian drug biperiden (Akineton(c)), an acetylcholine
antagonist with high affinity for muscarinic M1-type receptors, in four
consecutive cases of arousal disorder with sleepwalking and confusional behavior
in adolescents and adults with or without epilepsy who did not respond to
diazepam, clonazepam or amitriptyline. FINDINGS: The adjunctive use of biperiden
was associated with reduction or remission of sleepwalking episodes in four
consecutive treatment-refractory cases of arousal disorder with sleepwalking and
confusional behavior. In contrast, biperiden showed no effect in a patient with
REM behavioral disorder. INTERPRETATION: Although our observations do not and
cannot establish the efficacy or safety of biperiden, it may be useful to
consider biperiden for treatment of sleepwalking, if needed. A putative
cholinergic mechanism of arousal disorders, including sleepwalking, provides a
reasonable hypothesis why the anticholinergic agent biperiden might work.
Evidence for efficacy and safety from randomized controlled trials is needed to
confirm our preliminary observations.
PMID- 23153718
TI - Reliability and validity of the Korean version of the Neurological Disorders
Depression Inventory for Epilepsy (K-NDDI-E).
AB - The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) was
developed as a screening instrument for rapid detection of major depression in
people with epilepsy (PWE). We evaluated the reliability and validity of the
Korean version of the NDDI-E (K-NDDI-E) in Korean PWE. This study applied to 121
outpatients who underwent psychometric tests including the Mini International
Neuropsychiatric Interview-Plus Version 5.0.0, Beck Depression Inventory-II (BDI
II), and K-NDDI-E. The K-NDDI-E was easily comprehended and quickly completed by
the patients. Cronbach's alpha coefficient was 0.898. At a cut off score of 11,
the K-NDDI-E had a sensitivity of 84.6%, a specificity of 85.3%, a positive
predictive value of 61.1%, and a negative predictive value of 95.3%. The scores
of the K-NDDI-E had a positive correlation with those of the BDI-II (p<0.001). In
conclusion, the K-NDDI-E is a reliable and valid screening tool to detect major
depression in Korean PWE.
PMID- 23153719
TI - Signal-averaged and standard electrocardiography in patients with newly diagnosed
epilepsy.
AB - Antiepileptic drugs (AEDs) have been associated with cardiac conduction
abnormalities and arrhythmias, predominantly in patients with predisposing
cardiac conditions. Ventricular late potentials (VLPs) detected in the signal
averaged electrocardiogram (SAECG) may imply an increased risk of ventricular
tachycardia or fibrillation. Twenty-six AED-naive patients with newly diagnosed
epilepsy and no clinical evidence of heart disease were examined with SAECG and
standard ECG. Fifteen patients were treated with lamotrigine and ten with
carbamazepine. No significant abnormality was found in the standard ECG or SAECG
three to nine months after initiation of AED therapy. In one patient, a VLP was
detected at baseline and subsequent MRI demonstrated significant right
ventricular pathology; therefore, this patient was excluded from the rest of the
study. This exclusion along with only newly diagnosed patients with a low total
seizure count being included in the study may explain the lack of AED-induced
electrocardiographic abnormalities in this patient cohort.
PMID- 23153720
TI - Satisfaction with life domains in people with epilepsy.
AB - While commonly used quality-of-life instruments assess perceived epilepsy
associated limitations in life domains and formally document patient concerns,
less is known of community-dwelling adults with epilepsy about their satisfaction
with broader life domains, such as satisfaction with housing, education,
neighborhood, ability to help others, and achievement of goals. The purpose of
this study was to examine satisfaction with life domains in a representative
sample of community-dwelling adults with self-reported epilepsy from the 2008
HealthStyles survey. Following adjustment for sex, age group, race/ethnicity,
education, and income, people with epilepsy were more likely to report
frustration in the domains of achievement (e.g., dissatisfaction with education
and life goals), compromised social interactions (dissatisfaction with family
life, friends, and social life), and compromised physical capability
(dissatisfaction with health and energy level). Life satisfaction and other well
being domains can supplement health indicators to guide treatment and program
services for people with epilepsy to maximize their well-being.
PMID- 23153721
TI - Emotion processing bias and age of seizure onset among epilepsy patients with
depressive symptoms.
AB - The current study examined whether mood-congruent biases in emotion processing
extend to epilepsy patients with depressive symptoms and the potentially
moderating effects of age of seizure onset on these biases. In addition, we
examined associations between depression (Beck Depression Inventory - 2nd
Edition; BDI-II) and quality of life (Quality of Life in Epilepsy - 10-item
questionnaire; QOLIE-10). Data from 101 epilepsy patients were analyzed,
including 61 females and 40 males. Measures included the Comprehensive Affect
Testing System - Abbreviated (CATS-A), from which indices of mood-congruent bias
were derived. A significant interaction between BDI-II raw scores and age of
seizure onset was found for mood-congruent bias scores in the facial affect
modality (beta=-0.24, p<.03). Beck Depression Inventory - 2nd Edition raw scores
were significantly and positively correlated with quality of life (QOLIE-10;
r=.69, p<.01). Results of the current study show that epilepsy patients with an
early age of seizure onset may be most at risk for mood-congruent biases when
experiencing depressive symptoms and that such symptoms have real-world
implications for quality of life for persons living with epilepsy.
PMID- 23153722
TI - The Genetics of Sexuality and Aggression (GSA) twin samples in Finland.
AB - The Genetics of Sexuality and Aggression (GSA) project was launched at the Abo
Akademi University in Turku, Finland in 2005 and has so far undertaken two major
population-based data collections involving twins and siblings of twins. To date,
it consists of about 14,000 individuals (including 1,147 informative monozygotic
twin pairs, 1,042 informative same-sex dizygotic twin pairs, 741 informative
opposite-sex dizygotic twin pairs). Participants have been recruited through the
Central Population Registry of Finland and were 18-49 years of age at the time of
the data collections. Saliva samples for DNA genotyping (n = 4,278) and
testosterone analyses (n = 1,168) were collected in 2006. The primary focus of
the data collections has been on sexuality (both sexual functioning and sexual
behavior) and aggressive behavior. This paper provides an overview of the data
collections as well as an outline of the phenotypes and biological data assembled
within the project. A detailed overview of publications can be found at the
project's Web site: http://www.cebg.fi/.
PMID- 23153723
TI - Bias and error in understanding plant invasion impacts.
AB - Quantitative assessments of alien plant impacts are essential to inform
management to ensure that resources are prioritized against the most problematic
species and that restoration targets the worst-affected ecosystem processes.
Here, we present the first detailed critique of quantitative field studies of
alien plant impacts and highlight biases in the biogeography and life form of the
target species, the responses assessed, and the extent to which spatial
variability is addressed. Observed impacts often fail to translate to ecosystem
services or evidence of environmental degradation. The absence of overarching
hypotheses regarding impacts has reduced the consistency of approaches worldwide
and prevented the development of predictive tools. Future studies must ensure
that the links between species traits, ecosystem stocks, and ecosystem flows, as
well as ecosystem services, are explicitly defined.
PMID- 23153724
TI - Ecological intensification: harnessing ecosystem services for food security.
AB - Rising demands for agricultural products will increase pressure to further
intensify crop production, while negative environmental impacts have to be
minimized. Ecological intensification entails the environmentally friendly
replacement of anthropogenic inputs and/or enhancement of crop productivity, by
including regulating and supporting ecosystem services management in agricultural
practices. Effective ecological intensification requires an understanding of the
relations between land use at different scales and the community composition of
ecosystem service-providing organisms above and below ground, and the flow,
stability, contribution to yield, and management costs of the multiple services
delivered by these organisms. Research efforts and investments are particularly
needed to reduce existing yield gaps by integrating context-appropriate bundles
of ecosystem services into crop production systems.
PMID- 23153725
TI - Preparation and quality control of silver nanoparticle-antibody conjugate for use
in electrochemical immunoassays.
AB - Metal nanoparticle-antibody conjugates are often used as optical or
electrochemical markers in applications like immunohistochemistry, lateral flow
tests, biosensors and immunoassays. In order to serve that role, an antibody
needs to be immobilized on the surface of the nanoparticle. This is easily done,
as proteins bind to gold and silver nanoparticles spontaneously. However, this
immobilization process might result in nanoparticle aggregation or the loss of
the bioactivity of the conjugated antibodies. In this work the optimization of
antibody immobilization on silver colloid in order to obtain conjugates with the
best possible activity is investigated. The parameters investigated were the type
of immobilization buffer, its molarity and pH, the nanoparticle/antibody ratio
and also blocking and washing protocols to reduce non-specific binding. The
functionality of the obtained conjugates was tested with electrochemical
immunoassay. It was found out that the optimum environment for immobilization of
an anti-myoglobin antibody on silver nanoparticles was 0.2M boric acid pH 6.5
with 10 MUg of antibody loading per 1 mL of silver colloid. For an anti-troponin
antibody it was 0.1M boric acid pH 7.5 also with 10 MUg/mL of antibody loading.
The main problem for silver conjugation was the tendency of silver nanoparticles
to aggregate during the immobilization process, but by choosing the optimum
conditions the aggregation problem was completely removed. Here it is
demonstrated that by using the conjugates prepared with an optimized protocol an
increase in the sensitivity of the assay 10 times can be achieved. The
electrochemical immunoassay described here can be used as a test for quality
control of conjugates and for the estimation of batch-to-batch variability.
PMID- 23153726
TI - Fungal extracellular ribotoxins as insecticidal agents.
AB - Fungal ribotoxins were discovered almost 50 years ago as extracellular
ribonucleases (RNases) with antitumoral properties. However, the biological
function of these toxic proteins has remained elusive. The discovery of the
ribotoxin HtA, produced by the invertebrates pathogen Hirsutella thompsonii,
revived the old proposal that insecticidal activity would be their long searched
function. Unfortunately, HtA is rather singular among all ribotoxins known in
terms of sequence and structure similarities. Thus, it was intriguing to answer
the question of whether HtA is just an exception or, on the contrary, the
paradigmatic example of the ribotoxins function. The work presented uses HtA and
alpha-sarcin, the most representative member of the ribotoxins family, to show
their strong toxic action against insect larvae and cells.
PMID- 23153727
TI - Some challenges in forensic veterinary pathology: a review.
AB - Forensic veterinary pathology is a diverse discipline that is in an early phase
of its development. Common challenges include estimation of the age of skin
wounds and bruises, the diagnosis of drowning and estimation of the time since
death. However, many details of the pathological findings related to these
various aspects await validation. The 'multispecies' nature of veterinary
pathology, combined with the preponderance of published observations originating
from animal experimentation, rather than casework, poses two challenges. Firstly,
extrapolation of results between species may jeopardize the reliability (and
credibility) of the forensic opinion. Secondly, experimental studies may not
truly reflect the spectrum of changes seen in actual cases (e.g. extent of
injuries, infection, age and health of victim). With regard to drowning,
diagnosis based on post-mortem findings remains problematical. Methods for
estimation of the time since death (also known as the post-mortem interval)
continue to be a major focus of study, with fresh avenues such as post-mortem
diagnostic imaging offering interesting possibilities.
PMID- 23153728
TI - Prevalence of papillary changes and folliculosis of the palpebral conjunctiva in
asymptomatic Chinese children.
AB - PURPOSE: To determine the prevalence of papillary changes of the upper palpebral
conjunctiva and folliculosis of the lower palpebral conjunctiva in Chinese
children with no history of contact lens wear. METHOD: Ninety-nine subjects (aged
6-15 years old) who were interested in a myopia control study were screened for
papillary changes and folliculosis of the palpebral conjunctiva.
Photodocumentation was performed under white and blue light (after the
application of fluorescein) with a yellow filter and the photographs were graded
by a group of practitioners according to a pre-set grading scale. Analysis was
performed with the subjects divided into groups according to gender and age.
RESULTS: More than 48% of the subjects had clinically significant (>=Grade 3)
papillary changes in the upper palpebral conjunctiva. The prevalence of
significant folliculosis in the lower lid was about 33%. The prevalence of
significant papillary changes and folliculosis were similar between genders. No
differences were observed between younger (age<=10 years old) and older (age>10
years old) in papillary changes but younger subjects showed a higher prevalence
of folliculosis. CONCLUSIONS: The prevalences of clinically significant papillary
changes and folliculosis of unknown aetiology are high in Chinese children.
PMID- 23153729
TI - Homocysteine imbalance: a pathological metabolic marker.
AB - Perturbations in methyl group metabolism and homocysteine balance have emerged
over the past few decades as having defining roles in a number of pathological
conditions. Numerous nutritional, hormonal, and genetic factors that are
characterized by elevations in circulating homocysteine concentrations are also
associated with specific pathological conditions, including cancer development,
autoimmune diseases, vascular dysfunction, and neurodegenerative disease.
Although much remains to be explored, our understanding of the relationship
between disease, methyl balance, and epigenetic control of gene expression has
steadily progressed. However, homocysteine balance and its role in health and
disease are not as clearly understood. This review presents our current
understanding of homocysteine metabolism and its link to specific pathologies.
PMID- 23153730
TI - A review of calcium supplements and cardiovascular disease risk.
AB - A group of academic and industry experts in the fields of nutrition, cardiology,
epidemiology, food science, bone health, and integrative medicine examined the
data on the relationship between calcium supplement use and risk of
cardiovascular events, with an emphasis on 4 of the Bradford Hill criteria for
causal inference: strength, consistency, dose-response, and biological
plausibility. Results from 2 epidemiological studies and a meta-analysis of
randomized, controlled clinical trials, including a subgroup analysis from the
Women's Health Initiative, have prompted concern about a potential association
between calcium supplement use and a small increase in the risk of adverse
cardiovascular events. However, a number of issues with the studies, such as
inadequate compliance with the intervention, use of nontrial calcium supplements,
potential bias in event ascertainment, and lack of information on and adjustment
for known cardiovascular risk determinants, suggest that bias and confounding
cannot be excluded as explanations for the reported associations. Findings from
other cohort studies also suggest no detrimental effect of calcium from diet or
supplements, with or without vitamin D, on cardiovascular disease risk. In
addition, little evidence exists for plausible biological mechanisms to link
calcium supplement use with adverse cardiovascular outcomes. The authors do not
believe that the evidence presented to date regarding the hypothesized
relationship between calcium supplement use and increased cardiovascular disease
risk is sufficient to warrant a change in the Institute of Medicine
recommendations, which advocate use of supplements to promote optimal bone health
in individuals who do not obtain recommended intakes of calcium through dietary
sources.
PMID- 23153732
TI - History of zinc in agriculture.
AB - Zinc was established as essential for green plants in 1926 and for mammals in
1934. However, >20 y would pass before the first descriptions of zinc
deficiencies in farm animals appeared. In 1955, it was reported that zinc
supplementation would cure parakeratosis in swine. In 1958, it was reported that
zinc deficiency induced poor growth, leg abnormalities, poor feathering, and
parakeratosis in chicks. In the 1960s, zinc supplementation was found to
alleviate parakeratosis in grazing cattle and sheep. Within 35 y, it was
established that nearly one half of the soils in the world may be zinc deficient,
causing decreased plant zinc content and production that can be prevented by zinc
fertilization. In many of these areas, zinc deficiency is prevented in grazing
livestock by zinc fertilization of pastures or by providing salt licks. For
livestock under more defined conditions, such as poultry, swine, and dairy and
finishing cattle, feeds are easily supplemented with zinc salts to prevent
deficiency. Today, the causes and consequences of zinc deficiency and methods and
effects of overcoming the deficiency are well established for agriculture. The
history of zinc in agriculture is an outstanding demonstration of the translation
of research into practical application.
PMID- 23153731
TI - A historical review of progress in the assessment of dietary zinc intake as an
indicator of population zinc status.
AB - Dietary components influencing zinc (Zn) bioavailability were implicated in the
first cases of human Zn deficiency in the Middle East in the 1960s. It was not
until the 1980s that isotope tracer studies in humans quantified the effects of
the type and/or quantity of Zn, protein, iron, and phytate (myo-inositol
hexaphosphate) on Zn absorption in humans and confirmed the dose-dependent
inhibitory effect of phytate on Zn absorption. This led to further analysis of
the Zn and phytate content of foods. The use of phytate-to-Zn molar ratios as
likely estimates of absorbable dietary Zn followed together with an assessment of
their relationship with Zn biomarkers in low-income countries (LIC). In the
1990s, increasing knowledge of factors governing Zn-absorption diets led to
refinements of Zn requirements and algorithms to estimate dietary Zn
bioavailability. Their use highlighted that inadequate Zn intake from plant-based
diets were a major etiological factor in morbidity and stunting in LIC, prompting
the need to identify indicators of the population's Zn status. Major advances in
analyses of dietary data pioneered by Beaton in 1980s led to the endorsement in
2007 of a dietary Zn indicator based on the prevalence of the population with
usual Zn intake below the estimated average requirement for Zn. Risk of Zn
deficiency is a public health concern when the prevalence of inadequate Zn intake
is >25%. Recent findings that Zn bioavailability from high-phytate, whole-day
diets is lower than previous estimates suggest that revision of Zn estimated
average requirement for LIC may be warranted.
PMID- 23153733
TI - Scaling up of breastfeeding promotion programs in low- and middle-income
countries: the "breastfeeding gear" model.
AB - Breastfeeding (BF) promotion is one of the most cost-effective interventions to
advance mother-child health. Evidence-based frameworks and models to promote the
effective scale up and sustainability of BF programs are still lacking. A
systematic review of peer-reviewed and gray literature reports was conducted to
identify key barriers and facilitators for scale up of BF programs in low- and
middle-income countries. The review identified BF programs located in 28
countries in Africa, Latin America and the Caribbean, and Asia. Study designs
included case studies, qualitative studies, and observational quantitative
studies. Only 1 randomized, controlled trial was identified. A total of 22
enabling factors and 15 barriers were mapped into a scale-up framework termed
"AIDED" that was used to build the parsimonious breastfeeding gear model (BFGM).
Analogous to a well-oiled engine, the BFGM indicates the need for several key
"gears" to be working in synchrony and coordination. Evidence-based advocacy is
needed to generate the necessary political will to enact legislation and policies
to protect, promote, and support BF at the hospital and community levels. This
political-policy axis in turn drives the resources needed to support workforce
development, program delivery, and promotion. Research and evaluation are needed
to sustain the decentralized program coordination "gear" required for goal
setting and system feedback. The BFGM helps explain the different levels of
performance in national BF outcomes in Mexico and Brazil. Empirical research is
recommended to further test the usefulness of the AIDED framework and BFGM for
global scaling up of BF programs.
PMID- 23153735
TI - Nutritional translation blended with food science: 21st century applications.
AB - This paper, based on the symposium "Real-World Nutritional Translation Blended
With Food Science," describes how an integrated "farm-to-cell" approach would
create the framework necessary to address pressing public health issues. The
paper describes current research that examines chemical reactions that may
influence food flavor (and ultimately food consumption) and posits how these
reactions can be used in health promotion; it explains how mechanical engineering
and computer modeling can study digestive processes and provide better
understanding of how physical properties of food influence nutrient
bioavailability and posits how this research can also be used in the fight
against obesity and diabetes; and it illustrates how an interdisciplinary
scientific collaboration led to the development of a novel functional food that
may be used clinically in the prevention and treatment of prostate cancer.
PMID- 23153736
TI - Potassium.
PMID- 23153734
TI - The role of B vitamins in preventing and treating cognitive impairment and
decline.
AB - Many epidemiologic studies have considered whether markers of B-vitamin status
are associated with cognitive function and cognitive decline. This avenue of
research was sparked by the homocysteine (Hcy) theory of cardiovascular disease,
which was extended to Alzheimer's disease when a link between vascular dementia
and Alzheimer's disease was discovered. Hcy could cause cognitive impairment via
direct neurotoxicity. However, decreased remethylation of Hcy to methionine might
also compromise cognitive function by means other than mere Hcy lowering. Folate
and vitamin B-12 participate in Hcy remethylation and largely determine Hcy
status. Consequently, much of the relevant research has focused on these 2 B
vitamins. The many subtly different hypotheses that investigators have addressed
by attempting to link several B-vitamin status indicators to diverse cognition
related outcomes have created a confusing body of conflicting studies that seems
to defy summarization. Nevertheless, themes are discernible that aid
interpretation, foster hypothesis generation, and inform future study design. For
example, despite a shared metabolic pathway, Hcy, vitamin B-12, and folate are
differently related to specific cognitive outcomes. Although consistency of
findings across studies is often touted as essential to distinguishing causal
from coincidental relationships, discrepancies among study findings can be even
more informative.
PMID- 23153737
TI - Vitamin/trace mineral supplements for the elderly.
AB - The fraction of population that is elderly has been increasing, as has the
consumption of vitamin/trace mineral supplements, which is now a multibillion
dollar industry. Yet the rationale for such supplement intake by the majority may
be questioned. Some of the current recommendations for micronutrient intake by
the elderly are extrapolations from recommendations made for younger adults,
whereas other recommendations are based on measurements of biochemical indices
not proven to reflect a deficient level in the elderly. Suggestions that the
elderly need more than the recommended daily allowances largely rest on the
assumption that they should have biochemical indices similar to younger adults
despite decreased energy intake with decreased physical and metabolic activities
of the elderly. Although some individuals require supplementation because of
problems with intake, absorption, or metabolism, there is little or no proof that
boosting micronutrient intake above what can be achieved in well-balanced diets,
some of which already contain fortified foods, will lead to a healthier outcome
for most elderly individuals. There is not only the potential for unnecessary and
occasionally harmful excess administered to some, but there is a cost that now
runs in the billions of dollars and adds to the costs of covering multiple
chronic disease conditions. Hence, some caution should be exercised in public
health promulgations concerning routine use of supplements for those in this age
group (>65 y of age) and of both sexes until more research establishes clear
connections between the need for micronutrients and nutrient-related health in
the elderly.
PMID- 23153738
TI - Food and Nutrition Service, U.S. Department of Agriculture. Building a healthy
America: A profile of the supplemental nutrition assistance program. April 2012.
PMID- 23153740
TI - Strategic global approaches to improve breastfeeding rates.
PMID- 23153739
TI - Clinical nutrition update 2012.
PMID- 23153742
TI - Oral resveratrol and calcium fructoborate supplementation in subjects with stable
angina pectoris: effects on lipid profiles, inflammation markers, and quality of
life.
AB - OBJECTIVE: This study aimed to evaluate the effects of short-term (60-d) oral
supplementation with calcium fructoborate, resveratrol, and their combination on
the clinical and biological statuses of subjects with stable angina pectoris.
METHODS: A randomized, double-blinded, active-controlled, parallel clinical trial
was conducted in three groups of subjects. Of the total number of subjects
included in study (n = 166), 87 completed the 60-d test treatment study period
and 29 followed in parallel their usual medical care and treatment. The primary
outcomes were inflammation biomarkers (high-sensitivity C-reactive protein), left
ventricular function markers (N-terminal prohormone of brain natriuretic
peptide), and lipid markers (total cholesterol, low-density lipoprotein
cholesterol, high-density lipoprotein cholesterol, and triacylglycerols). Quality
of life was assessed by the Canadian Cardiovascular Society angina class and the
number of angina attacks per week. RESULTS: There was a significant decrease of
high-sensitivity C-reactive protein in all groups at the 30-d and 60-d visits.
This decrease was greater (39.7% at 60 d) for group 3 (calcium fructoborate),
followed by group 2 (resveratrol plus calcium fructoborate, 30.3% at 60 d). The N
terminal prohormone of brain natriuretic peptide was significantly lowered by
resveratrol (group 1, 59.7% at 60 d) and by calcium fructoborate (group 3, 52.6%
at 60 d). However, their combination (group 2) was the most effective and induced
a decrease of 65.5%. Lipid markers showed slight changes from baseline in all
groups. The improvement in the quality of life was best observed for subjects who
received the resveratrol and calcium fructoborate mixture (group 2). CONCLUSION:
The results indicate that the combination of resveratrol and calcium fructoborate
has beneficial effects in patients with angina
PMID- 23153743
TI - Dynamic sentinel lymph node biopsy in patients with invasive squamous cell
carcinoma of the penis: a prospective study of the long-term outcome of 500
inguinal basins assessed at a single institution.
AB - BACKGROUND: Dynamic sentinel node biopsy (DSNB) in combination with ultrasound
scan (USS) has been the technique of choice at our centre since 2004 for the
assessment of nonpalpable inguinal lymph nodes (cN0) in patients with squamous
cell carcinoma of the penis (SCCp). Sensitivity and false-negative rates may vary
depending on whether results are reported per patient or per node basin, and with
or without USS. OBJECTIVE: To determine the long-term outcome of patients
undergoing DSNB and USS-guided fine-needle aspiration cytology (FNAC) in our
cohort of newly diagnosed cN0 SCCp patients, as well as to analyse any variation
in sensitivity of the procedure. DESIGN, SETTING, AND PARTICIPANTS: A series of
consecutive patients with newly diagnosed SCCp, over a 6-yr period (2004-2010),
were analysed prospectively with a minimum follow-up period of 21 mo. All
patients had definitive histology of >= T1G2 and nonpalpable nodes in one or both
inguinal basins. Patients with persistent or untreated local disease were
excluded from the study. INTERVENTION: All eligible patients had DSNB and USS
with or without FNAC of cN0 groins. OUTCOME MEASUREMENTS AND STATISTICAL
ANALYSIS: The primary end point was no nodal disease recurrence on follow-up. The
secondary end point was complications after DSNB. Sensitivity of the procedure
was calculated per node basin, per patient, with DSNB alone, and with USS with
DSNB combined. RESULTS AND LIMITATIONS: Five hundred inguinal basins in 264
patients underwent USS with or without FNAC and DSNB. Seventy-three positive
inguinal basins (14.6%) in 59 patients (22.3%) were identified. Four inguinal
basins in four patients were confirmed false negative at 5, 8, 12, and 18 mo. Two
inguinal basins had positive USS and FNAC and negative DSNB results. Sensitivity
of DSNB with USS, with and without FNAC, per inguinal basin was 95% and per
patient was 94%. Sensitivity of DSNB alone per inguinal basin and per patient was
92% and 91%, respectively. The DSNB morbidity rate was 7.6%. CONCLUSIONS: DSNB in
combination with USS has excellent performance characteristics to stage patients
with cN0 SCCp, with a 5% false-negative rate per node basin and a 6% false
negative rate per patient.
PMID- 23153744
TI - Re: Steven Joniau, Laura Van den Bergh, Evelyne Lerut, et al. Mapping of pelvic
lymph node metastases in prostate cancer. Eur Urol. In press.
http://dx.doi.org/10.1016/j.eururo.2012.06.057.
PMID- 23153746
TI - Imaging evaluation of the parapharyngeal space.
AB - The authors present imaging anatomy of the parapharyngeal space. Imaging approach
is discussed in terms of the effect it has on differential diagnosis and
diagnosis by the otolaryngologist. Neoplastic and congenital lesions are
discussed along with other neck diseases occurring in this space.
PMID- 23153745
TI - Imaging anatomy of deep neck spaces.
AB - This article presents a comprehensive analysis of the neck fascia and neck spaces
that are formed by the interplay of the different fascial layers. Because a solid
and thorough understanding of the anatomy and relationship of the various neck
spaces is so valuable in diagnosing and treating diseases of the neck, this
information organizes the anatomic areas of the neck beginning with and overview,
followed by extent, anatomic relationship, and contents. Detailed enhanced
computed tomography images display the anatomic areas of the neck.
PMID- 23153747
TI - Masticator space: imaging anatomy for diagnosis.
AB - Masticator space anatomy and pathologic conditions are illustrated examples from
computed tomography and magnetic resonance imaging. Characteristic imaging
features of various disease processes are presented to aid the otolaryngologist
(head and neck surgeon) in diagnosis. The article describes infection, primary
neoplasm, metastatic disease, Osteonecrosis, and vascular anomalies.
PMID- 23153748
TI - Parotid space: anatomic imaging.
AB - The authors present imaging anatomy of the parotid space and discuss non
neoplastic lesions, autoimmune disorders, cysts, neoplastic lesions, epithelial
tumors, and nonepithelial lesions. They describe the diseases and their
appearance on imaging, describing how the differential diagnoses appear, along
with presenting examples of the images, primarily computed tomography and
magnetic resonance imaging.
PMID- 23153749
TI - Imaging of the carotid space.
AB - The most common of the lesions in the carotid space are discussed in relation to
their radiographic diagnosis and clinical implications. The appearance of tumors
and lesions on computed tomography or magnetic resonance imaging is presented,
and their differential diagnosis is discussed. The image of each carotid disease
is presented, and the discussion concludes with treatment recommendations and
considerations.
PMID- 23153750
TI - Retropharyngeal and prevertebral spaces: anatomic imaging and diagnosis.
AB - Cross-sectional imaging plays an important role in the evaluation of the
retropharyngeal space (RPS) and the prevertebral space (PVS). Because of their
deep location within the neck, lesions arising within these spaces are difficult,
if not impossible, to evaluate on clinical examination. This article details the
cross-sectional anatomy and imaging appearances of primary and secondary diseases
involving the RPS and PVS, including metastasis and spread from adjacent spaces.
The role of image-guided biopsy is also discussed.
PMID- 23153751
TI - Submandibular and sublingual spaces: diagnostic imaging and evaluation.
AB - The mylohyoid muscle divides the lower part of the oral cavity into 2 spaces: the
sublingual space, which is located superior to the muscle, and the submandibular
space, inferior to the muscle but superior to the hyoid bone. Although the
submandibular and sublingual spaces are small, a wide range of pathologic
processes may involve these spaces. They include cystic lesions, inflammatory
conditions with various causes, rare vascular lesions, and benign and malignant
neoplasms. This article outlines the radiologic anatomy of the region, describes
the various pathologic processes that may affect it, and discusses the use of
imaging in their evaluation.
PMID- 23153752
TI - Larynx: anatomic imaging for diagnosis and management.
AB - Imaging with CT, MRI, or fluorodeoxyglucose F 18-positron emission tomography is
often an important complement to laryngoscopy for diagnosis and management of
laryngeal pathology. At most centers, CT is the most popular modality for general
laryngeal imaging given its widespread availability, ease of acquisition, and
familiarity to clinicians, whereas MRI and positron emission tomography are used
as problem-solving tools. Frequent indications for laryngeal imaging include
cancer staging, suspected submucosal abnormalities, vocal cord paralysis,
laryngeal trauma, and laryngotracheal stenosis. This article reviews the primary
imaging modalities used for evaluation of, normal cross-sectional anatomy of, and
radiologic features of common diseases of the larynx.
PMID- 23153753
TI - Cervical lymph node evaluation and diagnosis.
AB - This article discusses the rationale for imaging cervical lymph nodes and reviews
nodal anatomy and common drainage patterns, imaging features of pathologic lymph
nodes, and the advantages of various imaging modalities available for evaluation
and diagnosis of the lymph nodes.
PMID- 23153754
TI - Lesions of the skull base: imaging for diagnosis and treatment.
AB - This article provides a summary of how to approach the imaging analysis of
lesions of the anterior, central, and posterior skull base. The primary focus is
tumors and tumor-mimickers, and representative examples are shown to
differentiate the features of lesions that can occur in the same location.
PMID- 23153755
TI - Postoperative and postradiation changes on imaging.
AB - The normal appearance of the posttherapy neck after common surgical procedures
and chemoradiation therapy is presented, with specific details for each surgical
procedure. Subsequently, the authors emphasize the recognition of complications
and disease recurrence with illustrated examples.
PMID- 23153756
TI - Interventional neuroradiology applications in otolaryngology, head and neck
surgery.
AB - A review of the current clinical applications of a variety of percutaneous and
endovascular interventional procedures of the extracranial head and neck is
presented. After a description of general principles and embolic agents for
interventional procedures, management of specific disorders is presented and
procedural steps are described for epistaxis, embolization of vascular head and
neck tumors, high-flow and low-flow cervical vascular malformations, head and
neck trauma and bleeding, radiofrequency ablation and cryoablation of tumors,
along with percutaneous biopsy within the head and neck.
PMID- 23153757
TI - Otolaryngology and radiology: partners in diagnosing and managing head and neck
disease.
PMID- 23153758
TI - Bilateral vision loss responsive to corticosteroids.
AB - A 48-year-old woman presented with painless bilateral vision loss that began in
the left eye and responded to steroids, followed by vision loss in the right eye
one day after completing her steroid taper. Diagnosis was complicated by a
positive screening test for Leber hereditary optic neuropathy and a negative
workup for demyelinating disease. Steroid-dependent optic neuropathies such as
autoimmune optic neuropathy and chronic relapsing inflammatory optic neuropathy
were considered in the differential. Seven months after initial presentation, the
patient developed a new periventricular white matter lesion, lesions on her
cervical and thoracic spinal cord, bilateral leg weakness, and sensory loss
consistent with multiple sclerosis.
PMID- 23153759
TI - Count sir Luigi Preziosi and his glaucoma operation: the development of early
glaucoma filtering surgery.
AB - Count Sir Luigi Preziosi (1888-1965) was a famous ophthalmologist from the island
Republic of Malta. He received his ophthalmic training in Rome and the United
Kingdom. He practiced ophthalmology in Malta for 45 years and was a professor at
the University of Malta. Like many physicians in Malta, he was active in the
politics and governance of his country, serving as president of the Senate,
president of the National Congress to draft a new constitution, and, finally, as
president of the National Assembly of Malta. His most important ophthalmologic
contribution was the development of the thermal sclerostomy filtering operation
for glaucoma, which he first described in 1924. He referred to this operation
initially as electro-cautery puncture and later simply as Preziosi's operation.
Many surgeons considered this procedure an advance over the other available
filtering operations such as sclerectomy, iridencleisis, and trephination. The
operation was then further developed in 1957 by Harold G. Scheie of the
University of Pennsylvania. Scheie referred to his procedure as peripheral
iridectomy with scleral cautery, and it was a standard filtering operation for
glaucoma for many years until the development of trabeculectomy.
PMID- 23153760
TI - Characterizing the antitumor response in mice treated with antigen-loaded
polyanhydride microparticles.
AB - Delivery of vaccine antigens with an appropriate adjuvant can trigger potential
immune responses against cancer leading to reduced tumor growth and improved
survival. In this study, various formulations of a bioerodible amphiphilic
polyanhydride copolymer based on 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane
(CPTEG) and 1,6-bis(p-carboxyphenoxy) hexane (CPH) with inherent adjuvant
properties were evaluated for antigen-loading properties, immunogenicity and
antitumor activity. Mice were vaccinated with 50:50 CPTEG:CPH microparticles
encapsulating a model tumor antigen, ovalbumin (OVA), in combination with the
Toll-like receptor-9 agonist, CpG oligonucleotide 1826 (CpG ODN). Mice treated
with OVA-encapsulated CPTEG:CPH particles elicited the highest CD8(+) T cell
responses on days 14 and 20 when compared to other treatment groups. This
treatment group also displayed the most delayed tumor progression and the most
extended survival times. Particles encapsulating OVA and CpG ODN generated the
highest anti-OVA IgG(1) antibody responses in mice but these mice did not show
significant tumor protection. These results suggest that antigen-loaded CPTEG:CPH
microparticles can stimulate antigen-specific cellular responses and could
therefore potentially be used to promote antitumor responses in cancer patients.
PMID- 23153761
TI - The effects of interactive mechanical and biochemical niche signaling on
osteogenic differentiation of adipose-derived stem cells using combinatorial
hydrogels.
AB - Stem cells reside in a multi-factorial environment containing biochemical and
mechanical signals. Changing biochemical signals in most scaffolds often leads to
simultaneous changes in mechanical properties, which makes it difficult to
elucidate the complex interplay between niche cues. Combinatorial studies on cell
material interactions have emerged as a tool to facilitate analyses of stem cell
responses to various niche cues, but most studies to date have been performed on
two-dimensional environments. Here we developed three-dimensional combinatorial
hydrogels with independent control of biochemical and mechanical properties to
facilitate analysis of interactive biochemical and mechanical signaling on
adipose-derived stem cell osteogenesis in three dimensions. Our results suggest
that scaffold biochemical and mechanical signals synergize only at specific
combinations to promote bone differentiation. Leading compositions were
identified to have intermediate stiffness (~55kPa) and low concentration of
fibronectin (10MUg ml(-1)), which led to an increase in osteocalcin gene
expression of over 130-fold. Our results suggest that scaffolds with
independently tunable niche cues could provide a powerful tool for conducting
mechanistic studies to decipher how complex niche cues regulate stem cell fate in
three dimensions, and facilitate rapid identification of optimal niche cues that
promote desirable cellular processes or tissue regeneration.
PMID- 23153762
TI - Synergistic antivirus effect of combined administration of Combivir with Angelica
polysaccharide sulfate.
AB - This study is to investigate the synergistic effect of Anglica polysaccharide
sulfate (APS-1) and Combivir, an anti-AIDS drug, on murine leukemia virus in
vivo. As the results shown, the virus replication was significantly decreased by
the combination of APS-1 and Combivir, which tended to be further decreased (58%
inhibition) when compared with that of Combivir alone (51% inhibition).
Furthermore, both the percentage of CD4(+) cells and CD4(+)/CD8(+) ratio in
peripheral blood cells were significantly enhanced by this combined
administration, while the CD4(+) cells was only slightly increased and
CD4(+)/CD8(+) ratio was not affected by Combivir alone. Additionally, combination
of APS-1 and Combivir also alleviated the toxicity of Combivir. APS-1 not only
increased the survival rate of mice administered with LD(50) dose of Combivir,
but also reduced the hematologic toxicity induced by Combivir, RBC, HGB and PLT
were restored to normal level. These results suggest that APS-1 had synergistic
effect with Combivir, which provided new insight into the potential clinical use
of polysaccharide sulfate in anti-AIDS field.
PMID- 23153763
TI - Probing the molecular determinant of the lipase-specific foldase Lif26 for the
interaction with its cognate Lip26.
AB - As a steric chaperone, the lipase-specific foldase Lif26 from Acinetobacter sp.
XMZ-26 is required for correct folding of the lipase Lip26 in in vivo co
expression and in vitro refolding systems. Lif26 interacts with Lip26 as
determined by yeast two hybrid assays in vivo and GST pull-down experiments in
vitro. To study the molecular determinants of the interaction between Lif26 and
Lip26, a homology model-based screening of residues, molecular dynamics (MD)
simulation-based calculation of interaction energies, and site-directed
mutagenesis to alter individual screened residues were applied. One conserved
amino acid in the C-terminal mini-domain of Lif26, Arg332, was involved in the
interaction with Lip26. Arg332 could not be replaced by any other residue, based
on saturated site-directed mutagenesis, and it formed a conserved and stable salt
bridge with Glu112 of Lip26, which may contribute to binding specificity. The
residues surrounding Arg332, such as Trp288 in alpha9, likely stabilized Arg332
in the proper conformation for the interaction with Lip26.
PMID- 23153764
TI - Modelling (18)O2 and (16)O2 unidirectional fluxes in plants. III: fitting of
experimental data by a simple model.
AB - Photosynthetic assimilation of CO2 in plants results in the balance between the
photochemical energy developed by light in chloroplasts, and the consumption of
that energy by the oxygenation processes, mainly the photorespiration in C3
plants. The analysis of classical biological models shows the difficulties to
bring to fore the oxygenation rate due to the photorespiration pathway. As for
other parameters, the most important key point is the estimation of the electron
transport rate (ETR or J), i.e. the flux of biochemical energy, which is shared
between the reductive and oxidative cycles of carbon. The only reliable method to
quantify the linear electron flux responsible for the production of reductive
energy is to directly measure the O2 evolution by (18)O2 labelling and mass
spectrometry. The hypothesis that the respective rates of reductive and oxidative
cycles of carbon are only determined by the kinetic parameters of Rubisco, the
respective concentrations of CO2 and O2 at the Rubisco site and the available
electron transport rate, ultimately leads to propose new expressions of
biochemical model equations. The modelling of (18)O2 and (16)O2 unidirectional
fluxes in plants shows that a simple model can fit the photosynthetic and
photorespiration exchanges for a wide range of environmental conditions. Its
originality is to express the carboxylation and the oxygenation as a function of
external gas concentrations, by the definition of a plant specificity factor Sp
that mimics the internal reactions of Rubisco in plants. The difference between
the specificity factors of plant (Sp) and of Rubisco (Sr) is directly related to
the conductance values to CO2 transfer between the atmosphere and the Rubisco
site. This clearly illustrates that the values and the variation of conductance
are much more important, in higher C3 plants, than the small variations of the
Rubisco specificity factor. The simple model systematically expresses the
reciprocal variations of carboxylation and oxygenation exchanges illustrated by a
"mirror effect". It explains the protective sink effect of photorespiration, e.g.
during water stress. The importance of the CO2 compensation point, in classical
models, is reduced at the benefit of the crossing points Cx and Ox, concentration
values where carboxylation and oxygenation are equal or where the gross O2 uptake
is half of the gross O2 evolution. This concept is useful to illustrate the
feedback effects of photorespiration in the atmosphere regulation. The constancy
of Sp and of Cx for a great variation of P under several irradiance levels shows
that the regulation of the conductance maintains constant the internal CO2 and
the ratio of photorespiration to photosynthesis (PR/P). The maintenance of the
ratio PR/P, in conditions of which PR could be reduced and the carboxylation
increased, reinforces the hypothesis of a positive role of photorespiration and
its involvement in the plant-atmosphere co-evolution.
PMID- 23153765
TI - [Care pathways and physical and rehabilitation medicine, an update].
PMID- 23153766
TI - Endoscopic thoracic sympathectomy for primary hyperhidrosis: a 16-year follow up
in a single UK centre.
AB - INTRODUCTION: Since the introduction of Endoscopic Thoracic Sympathectomy ( ETS )
by Kux in 1951, the procedure has been performed for treatment of primary
hyperhidrosis (PH) of the upper limb. Despite its initial success and minimally
invasive nature, the long-term results are yet to be established. The aim of this
study is to evaluate the outcome of patients after ETS with particular emphasis
on patient satisfaction and its effectiveness over a 16-year period. METHODS: A
patient survey of fifty-one (n = 51) patients who had ETS for PH of palms from
1995 to 2011 was conducted. The data on age, sex, site of the PH, family history,
trigger, hospital stay, relief from symptoms, complications, refractory sweating
and overall satisfaction with the procedure was analysed with SAS software
version 9.1.3. CONCLUSION: The mean follow-up was 77 months (range, 6-189 months)
with equal gender distribution (n = 24 males Vs n = 27 females) and mean age of
19 (range, 13-64 years). The hereditary prevalence was 55%. Forty-six patients
(90.2%) reported an immediate (<=24 h) and four patients (7.8%) reported a delay
(>24 h) in relief of symptoms. To the best of our knowledge this is longest
duration of follow-up reported in the literature.
PMID- 23153767
TI - [Ocular phototoxicity and altitude among mountain guides].
AB - PURPOSE: This study aimed to evaluate ocular phototoxicity in mountaineer guides
who experience overexposure to ultraviolet related to the altitude at which they
work, as well as light reflection on snow. MATERIALS AND METHODS: Ninety-six
guides and 90 controls living in plains, over 50 years old, underwent complete
examinations. They responded to a questionnaire assessing altitude exposure and
protective eyewear. We compared the two groups and performed a logistic
regression within the guide group so as to identify risk and protective factors.
RESULTS: Guides develop more ocular surface diseases. They exhibit more anterior
cortical cataract (P<0.01) and cataract surgery (P=0.01). Only 61.5% of guides
had a normal ocular fundus versus 81.1% in control group (P<0.01). They exhibit
more drusen (27.2% vs. 15.6%, P<0.01). Among the guide group, exposure at an
altitude above 3000 m is risk factor for anterior cortical cataract (OR=1.16,
P<0.01). Wearing ski masks (OR=0.50, P=0.04) or photochromic lenses (OR=0.53,
P=0.03) reduces this risk. Exposure to snow increases the risk of maculopathy
(OR=1.9, P<0.01). Wearing a hat reduces this risk (OR=0.40, P=0.02) and the risk
of cataract formation (OR=0.46, P=0.04). CONCLUSIONS: Guides develop more ocular
surface diseases, anterior cortical lens opacities and drusen. These results
underscore the potential deleterious role of ultraviolet radiation and the
importance of light reflection on snow. The best ocular protection includes
sunglasses and a hat with a visor or brim.
PMID- 23153768
TI - Impact of glutathione S-transferase T1 gene polymorphisms on acute cellular
rejection in living donor liver transplantation.
AB - It has previously been demonstrated that glutathione S-transferase T1 (GSTT1)
genetic mismatch between recipient and donor is a risk factor for developing
immune-mediated hepatitis following liver transplantation and for antibody
mediated rejection in renal transplantation. Little is known whether the GSTT1
gene polymorphism affects the incidence of acute cellular rejection (ACR)
following living donor liver transplantation (LDLT). Patients underwent LDLT at
Nagoya University or Kyoto University, Japan, between 2004 and 2009. Genotyping
of GSTT1 genes (null or present genotype) was conducted in recipients and donors.
A total of 155 LDLT cases were examined. Forty-seven recipients (30.3%) developed
early ACR. There was no association of recipient GSTT1 genotype with ACR
incidence. However, ACR incidence was significantly higher in recipients
transplanted from GSTT1 present genotype donors than in those transplanted from
GSTT1 null genotype donors [odds ratio (OR)=2.64, 95% confidence interval
(CI)=1.12-5.83, p=0.016]. Moreover, GSTT1 recipient/donor genotype mismatch
(present/null or null/present) was significantly associated with ACR development
(OR=2.28, 95% CI=1.12-4.61, p=0.022). The genotyping of GSTT1 in recipients and
donors might be useful to stratify the liver transplant recipients according to
risk of ACR.
PMID- 23153769
TI - Impact of NF-kappaB gene polymorphism on allograft outcome in Hispanic renal
transplant recipients.
AB - BACKGROUND: The dimeric NF-kappaB transcription factors play critical roles in
diverse cellular processes including adaptive and innate immunity, cell
differentiation, proliferation and apoptosis. It regulates the expression of
numerous genes that play a key role in the inflammatory response during kidney
allograft rejection. This study aims to determine the association of NF-kappaB
gene polymorphisms with allograft outcomes in the Hispanic renal transplant
recipients. METHODS: A total of 607 Hispanic renal transplant recipients at St.
Vincent Medical Center between 2001 and 2010 were included in this study. The NF
kappaB genotypes were studied along with clinical data. In the case of NF-kappaB
genotypes, the following single nucleotide polymorphisms (SNPs) were included: NF
kappaB1 (rs3774959, rs3774932, rs3774937, rs230526, rs230519), NF-kappaB2
(rs1056890, rs7897947, rs12769316) and NF-kappaB inducing kinase (NIK)
(rs9908330, rs7222094). The association of each genotype with renal allograft
survival and acute rejection was evaluated. RESULTS: NF-kappaB1 (rs3774937) CC
genotype showed protective association with allograft rejection (OR=0.66, 95%
CI=0.44-0.99, p=0.04). There was a significant increase in allograft survival
time associated with the NF-kappaB1 (rs3774959) A allele (OR=0.76, 95% CI=0.60
0.98, p=0.03) while GG genotype was associated with a higher risk of graft
failure (OR=1.51, 95% CI=1.02-2.21, p=0.03). There were no associations between
polymorphic markers in NF-kappaB2 and NIK genes with allograft survival or acute
rejection. Among non-genetic factors, we found that the use of tacrolimus, a
deceased donor, delayed graft function and acute rejection were associated with
allograft failure. CONCLUSION: The result of present study suggests that NF
kappaB1 gene polymorphisms may determine the incidence of acute rejection or
graft survival among Hispanic allograft recipients.
PMID- 23153770
TI - Presacral schwannoma.
AB - Presacral schwannoma is a rare tumor, diagnosed essentially by pelvi-rectal
digital examination. Diagnostic investigations should include initial CT-scan
followed by pelvic MRI. The role of angiography and preoperative biopsy remain
debated. Management is surgical: several surgical routes are possible to remove
the tumor; resection essentially consists of enucleation.
PMID- 23153771
TI - Single umbilical incision laparoscopic cholecystectomy: results of the
prospective trial of the Coelio Club.
AB - AIM: To assess the cosmetic outcome after single umbilical incision laparoscopic
cholecystectomies (SILC) performed by the surgeons of the Coelio Club. PATIENTS
AND METHODS: Multicenter prospective study concerning 105 consecutive patients
operated between December 2009 and February 2011 by SILC for non-complicated
gallstones. Perioperative and postoperative parameters were analyzed with a
systematic follow-up at 1 and 6months postoperative. RESULTS: Conversion to
conventional laparoscopic cholecystectomy (CLC) was required for six patients
(5.7%). Conversion rate is higher in case of acute cholecystitis (25%, P<0.001).
Cosmetic outcome is found excellent by the patient (in 86% of the cases at
6months) and by the surgeon (in 90% of the cases at 6months) using an EVA scale.
An incisional hernia was found in two cases (1.9%) and a superficial wound
infection in four cases (3.8%). CONCLUSIONS: The cosmetic outcome after SILC is
found excellent. SILC has its place in the surgical management of the non
complicated gallstone. We did not notice higher level of peroperative
complications (biliary tract injury) during SILC than during CLC. Postoperative
higher level of abdominal wall complications than after a CLC makes the surgeon
caution to a careful abdominal wall closure.
PMID- 23153772
TI - Opportunities for policy interventions to reduce youth hookah smoking in the
United States.
AB - Preventing youth smoking initiation is a priority for tobacco control programs,
because most adult tobacco smokers become addicted during adolescence.
Interventions that restrict the affordability, accessibility, and marketing of
cigarettes have been effective in reducing youth cigarette smoking. However,
increasing numbers of youth are smoking tobacco using hookahs. Predictors of
smoking tobacco with hookahs are the same as those for smoking cigarettes.
Established interventions that curb youth cigarette smoking should therefore be
effective in reducing hookah use. Potential policy interventions include
equalizing tobacco tax rates for all tobacco types, requiring warning labels on
hookah tobacco and accurate labeling of product contents, extending the cigarette
flavoring ban to hookah tobacco, enacting smoke-free air laws and removing
exemptions for hookah lounges, and expanding shipping restrictions on tobacco
products.
PMID- 23153773
TI - Prevalence of high body mass index among children and adolescents at a US
military treatment facility, 2008-2009.
AB - We assessed the prevalence of high body mass index (BMI) in a large cohort of
military children. We compared BMI data from electronic medical records of
military children aged 2 to 18 years with BMI data from the National Health and
Nutrition Examination Survey (NHANES). The 23,778 military children studied were
significantly less likely than the NHANES children to be overweight (27.1% vs
31.8%) or obese (11.9% vs 16.9%). Even though military parents are required to
maintain fitness and weight standards, the absolute difference between military
and civilian children was small.
PMID- 23153774
TI - Regulation of apical growth and hyphal branching in Streptomyces.
AB - The filamentous bacteria Streptomyces grow by tip extension and through the
initiation of new branches, and this apical growth is directed by a polarisome
like complex involving the essential polarity protein DivIVA. New branch sites
must be marked de novo and, until recently, there was no understanding of how
these new sites are selected. Equally, hyphal branching patterns are affected by
environmental conditions, but there was no insight into how polar growth and
hyphal branching might be regulated in response to external or internal cues.
This review focuses on recent discoveries that reveal the principal mechanism of
branch site selection in Streptomyces, and the first mechanism to be identified
that regulates polarisome behaviour to modulate polar growth and hyphal
branching.
PMID- 23153775
TI - Enhanced degradation of 2-nitrotoluene by immobilized cells of Micrococcus sp.
strain SMN-1.
AB - Nitrotoluenes are the toxic pollutants of the environment because of their large
scale use in the production of explosives. Biodegradation of such chemicals by
microorganisms may provide an effective method for their detoxification. We have
studied the degradation of 2-nitrotoluene by cells of Micrococcus sp. strain SMN
1 immobilized in various matrices such as polyurethane foam (PUF), sodium
alginate (SA), sodium alginate-polyvinyl alcohol (SA-PVA), agar and
polyacrylamide. The rate of degradation of 15 and 30 mM 2-nitrotoluene by freely
suspended cells and immobilized cells in batches and fed-batch with shaken
cultures were compared. The PUF-immobilized cells achieved higher degradation of
15 and 30 mM 2-nitrotoluene than freely suspended cells and the cells immobilized
in SA-PVA, polyacrylamide, SA and agar. The PUF-immobilized cells could be reused
more than 24 cycles without loosing their degradation capacity and showed more
tolerance to pH and temperature changes than freely suspended cells. These
results revealed the enhanced rate of degradation of 2-nitrotoluene by PUF
immobilized cells of Micrococcus sp. strain SMN-1.
PMID- 23153776
TI - Application of ozone for the removal of bisphenol A from water and wastewater--a
review.
AB - The extensive use of Bisphenol A (BPA) in the plastics industry has led to
increasing reports of its presence in the aquatic environment, with
concentrations of ng L(-1) to MUg L(-1). Various advanced oxidation processes,
including ozonation, have been shown to effectively degrade BPA. This paper
reviews the current advancements in using ozone to remove BPA from water and
wastewater. Most of the published work on the oxidation of BPA by ozone has
focused on the efficiency of BPA removal in terms of the disappearance of BPA,
and the effect of various operational parameters such as ozone feed rate, contact
time and pH; some information is available on the estrogenic activity of the
treated water. Due to increasing operational reliability and cost effectiveness,
there is great potential for industrial scale application of ozone for the
treatment of BPA. However, there is a significant lack of information on the
formation of oxidation by-products and their toxicities, particularly in more
complex matrices such as wastewater, and further investigation is needed for a
better understanding of the environmental fate of BPA.
PMID- 23153777
TI - Tributyltin exposure causes lipotoxicity responses in the ovaries of rockfish,
Sebastiscus marmoratus.
AB - Tributyltin (TBT) is a well-studied endocrine disruptor in mollusks and fishes.
Recently, TBT is also recognized as a metabolic disruptor. Since abnormal lipids
metabolism can induce negative effects on reproduction, the present study was
designed to investigate the effects of TBT on ovarian lipid accumulation and
testosterone esterification in rockfish (Sebastiscus marmoratus). After exposure
for 48 d, there was a decrease of neutral lipid droplets in the ooplasm of
ovaries. Exposure has also induced lipotoxicity responses in the ovaries, which
shown as an increase of interstitial ectopic lipid accumulation and total lipids.
The decrease of serum triiodothyronine and thyroxine concentrations might be
responsible for the lipotoxicity responses. In addition, the percentage of
testosterone in an esterified form was significantly decreased in the ovaries by
TBT exposure, which might be a mechanism by which free testosterone levels
increased. The accumulation of ectopic lipids and increase of free testosterone
levels in the ovaries might impact ovarian functions and oocyte development in
fish. These results strongly indicate that TBT exposure can influence
reproductive functions of rockfish through lipotoxic mechanism.
PMID- 23153778
TI - [Invasion of the spinal column by a posterior mediastinal cavernous haemangioma:
a combined surgical approach].
PMID- 23153779
TI - [Afferent loop stimulation prior to ileostomy closure].
AB - There is a 17% complications rate after ileostomy closure, with paralytic ileus
being the most common. With the aim of reducing this complication, stimulation
via the afferent loop was performed daily for the 2 weeks prior to the stoma.
PMID- 23153780
TI - [Evaluation of the gastrointestinal quality of life index as a system to
prioritize patients on the waiting list for laparoscopic cholecystectomy].
AB - INTRODUCTION: We prospectively evaluated health-related quality of life (HRQoL)
through the gastrointestinal quality of life index (GIQLI) as a system to
prioritize patients on the waiting list for laparoscopic cholecystectomy (LC) and
its correlation with a linear prioritization system developed in the General and
Gastrointestinal Surgery Institute of Clinica Quiron in Valencia. MATERIAL AND
METHODS: There were 100 consecutive patients who underwent elective outpatient
LC. The main outcome measures consisted of: 1) assessment of the impact of the
disease, measured through the GIQLI; 2) evaluation of an objective system based
on technical scientific criteria; 3) evaluation of the utility of LC in improving
HRQoL through the GIQLI by analyzing expected and obtained utility through the
change ratio, and 4) analysis of the correlation between the objective linear
system, HRQoL and utility. RESULTS: The GIQLI was useful in evaluating the impact
of the disease. LC significantly improved HRQoL in both oligosymptomatic and
symptomatic patients. The objective or clinical factors did not allow perceptions
of the process to be evaluated or the impact on HRQoL to be measured or inferred.
A prioritization system based on GIQLI scores allows patients to be selected
according to the expected utility (worsening of HRQoL) and obtained utility
(improvement in HRQoL) of CL. CONCLUSIONS: Prioritization systems should include
utility to guarantee equity. The GIQLI shows the impact of the disease on the
patient while the clinical/objective factors are unrelated to the expectation of
prioritization. Prioritization systems should include both elements to maintain
the balance between impact and appropriate indication.
PMID- 23153781
TI - Clinical implications of novel variants of the fibularis (peroneus) quartus
muscle inserting onto the cuboid bone: peroneocuboideus and
peroneocalcaneocuboideus.
AB - Two variants of the fibularis (peroneus) quartus muscle were identified and
photographed in the legs of a 70-year-old white male cadaver. A rare
peroneocuboideus (fibulocuboideus) muscle (as described by Chudzinski) and a
novel peroneocalcaneocuboideus (fibulocalcaneocuboideus) muscle was found in the
right and left leg, respectively. The latter muscle has not been previously
reported and was termed "peroneocalcaneocuboideus" on the basis of its origin and
insertions. Also, the distal attachment of both muscles inserted onto the distal
lip of the peroneal sulcus of the cuboid bone, which differs from the historical
data. The insertion of the peroneocuboideus muscle was previously described as
being at the tuberosity of the cuboid bone or, simply, the lateral surface of the
cuboid. Therefore, the present case study provides the first gross anatomic
photographs of these variant leg muscles along their entire length, identifies a
novel fibularis quartus variant, and describes a new insertion site for the
peroneocuboideus muscle. Throughout our report, the historical data are reviewed
to list the prevalence and describe the clinical implications of the fibularis
quartus muscle and its variants. The presence of variant fibularis quartus
muscles has been known to cause lateral ankle pain and stenosis, ankle
instability, fibular tenosynovitis, subluxation of the fibular (peroneal)
tendons, and longitudinal splitting of the fibularis brevis tendon in radiologic
and case studies. Therefore, surgeons, radiologists, and clinicians should be
aware of these variant muscles when considering various diagnoses, interpreting
radiographs, and pursuing surgical intervention to relieve lateral ankle
pathologic features.
PMID- 23153782
TI - Perioperative complications of a modular stem fixed-bearing total ankle
replacement with intramedullary guidance.
AB - Despite improved total ankle replacement outcomes, investigators have
demonstrated that the incidence of complications after total ankle replacement is
a function of the surgeon's experience with the technique. We hypothesized that
the use of an intramedullary guide during a modular stem fixed-bearing total
ankle replacement would decrease the incidence of perioperative complications and
produce a similar incidence of complications across time. Because all patients
were mobilized early, we also evaluated the influence of early mobilization on
wound development. The medical records were reviewed to identify complications,
and the radiographs were evaluated to determine the component alignment of the
initial 58 consecutive ankles. Major wound complications were defined as
complications requiring soft tissue coverage by a plastic surgeon. Minor wound
complications were defined as those that could be treated without a return to the
operating room. The procedures were separated into 2 groups: the initial 29
procedures (group A) and latter 29 procedures (group B). Eight ankles (14%) had
wound complications. The incidence of complications was similar across time [r(s)
(56) = -0.06, p = .64]. The incidence of complications and component misalignment
was similar for groups A and B (p >= .19). All wounds were diagnosed within 15
days of surgery. None of the ankles developed wounds after physical therapy
began. These results have demonstrated that the modular stem fixed-bearing total
ankle replacement with intramedullary guidance can produce a similar incidence of
complications over time, regardless of surgeon experience. Additionally, early
mobilization did not appear to influence the incidence of wound complications and
should be advocated, when appropriate.
PMID- 23153783
TI - Talar neck fractures: a systematic review of the literature.
AB - Considerable controversy surrounds the management of talar neck fractures
regarding the rate of post-traumatic arthrosis, secondary procedures, avascular
necrosis, and the effect of the interval to surgery on these variables. A data
search using PubMed was performed with the keywords "talus" and "fracture." The
search found 1280 studies. Ultimately, 21 reports involving 943 talar neck
fractures were analyzed. Data concerning open fractures, the interval to surgery
and its relationship to the incidence of avascular necrosis, and the rates of
malunion and nonunion, post-traumatic arthrosis, secondary salvage procedures,
and functional outcomes were collected and analyzed. The variables examined were
not uniformly reported in all studies. The overall rate of avascular necrosis was
33%, with no demonstrated relationship between the interval to surgery and the
rate of avascular necrosis. Malunion occurred approximately 17% of the time, with
nonunion occurring approximately 5% of the time. Post-traumatic arthrosis
occurred in 68% of patients, although secondary salvage procedures were only
performed in 19% of patients. Functional outcomes were difficult to assess, given
the variability of reported outcomes and unvalidated measures. The optimal
management of talar neck fractures has yet to be determined. Although the present
review has improved understanding of these difficult fractures, additional
studies that use validated outcomes measures are warranted to determine the
effect of delayed surgery on final outcomes and optimal treatment methods.
PMID- 23153784
TI - Subtalar joint septic arthritis in a patient with hypogammaglobulinemia.
AB - The clinical presentation of a monoarticular, red, hot, and swollen joint has
many possible diagnoses, including septic arthritis, which is 1 of the most
devastating. The morbidity associated with this pathologic process involves
permanent joint damage and the potential for progression to systemic illness and,
even, mortality. The common risk factors for joint sepsis include a history of
rheumatoid arthritis, previous joint surgery, joint prosthesis, intravenous drug
abuse, alcoholism, diabetes, previous intra-articular steroid use, and cutaneous
ulceration. The diagnosis is primarily determined from the culture results after
arthrocentesis and correlation with direct visualization, imaging, and various
serologies, including synovial analysis. In the present report, a case of an
insidious presentation of subtalar joint septic arthritis and its association
with a unique patient presentation concomitant with primary immunodeficiency and
culture-proven Myocplasma hominis infection is discussed. Septic arthritis has a
predilection for the lower extremities and typically is isolated to the hip or
knee, with less common involvement of the ankle or metatarsophalangeal joints.
Owing to the uncommon nature of primary immunodeficiency disorders and the
paucity of studies discussing their association with septic arthridites, we aimed
to raise awareness of subtalar joint septic arthritis and to provide a brief
overview of the pathogenesis as it presented in a 33-year-old male with X-linked
hypogammaglobulinemia/agammaglobulinema.
PMID- 23153785
TI - Skeletal and dental stability of segmental distraction of the anterior mandibular
alveolar process. A 5.5-year follow-up.
AB - 17 patients (14 female; 3 male) were analysed retrospectively for skeletal and
dental relapse before distraction osteogenesis (DO) of the mandibular anterior
alveolar process at T1 (17.0 days), after DO at T2 (mean 6.5 days), at T3 (mean
24.4 days), at T4 (mean 2.0 years), and at T5 (mean 5.5 years). Lateral
cephalograms were traced by hand, digitized, superimposed, and evaluated.
Skeletal correction (T5-T1) was mainly achieved through the distraction of the
anterior alveolar segment in a rotational manner where the incisors were more
proclined. The horizontal backward relapse (T5-T3) measured -0.3mm or 8.3% at
point B (non-significant) and -1.8mm or 29.0% at incision inferior (p<0.01). Age,
gender, amount and type (rotational vs. translational) of advancement were not
correlated with the amount of relapse. High angle patients (NL/ML'; p<0.01)
showed significant smaller relapse rates at point B. Overcorrection of the
overjet achieved by the distraction could be a reason for dental relapse.
Considering the amount of long-term skeletal relapse the DO could be an
alternative to bilateral sagittal split osteotomy for mandibular advancement in
selected cases.
PMID- 23153786
TI - Rehabilitation of edentulous posterior atrophic mandible: inferior alveolar nerve
lateralization by piezotome and immediate implant placement.
AB - The height and consistency of the bone tissue located above the inferior alveolar
nerve (IAN) represents an important challenge when a patient's atrophied
posterior mandible is rehabilitated with an osseointegrated implant. Usually, the
surgical reconstruction of atrophic ridges is performed using several different
techniques. The purpose of this study is to demonstrate the effectiveness and
safety of the inferior alveolar nerve lateralization (IANL) technique performed
with ultrasonic cutting technology (piezotome). To demonstrate this, 38
osseointegrated implants (11-15 mm in length) were performed during 19 procedures
on 15 different patients. After 8 weeks, 14 of those 15 patients (18 of 19 sites:
94.73%) showed normal IAN function. The implant success rate was 97.36%.
PMID- 23153787
TI - Bone anchoring of sutures for adequate repositioning of the soft tissue flaps in
one stage dental implants.
AB - The choice of suture material and technique is important to optimize wound
healing. If surgical wound edges are not properly approximated healing may be
delayed because blood may accumulate under the flap and separate it from the
underlying bone. The authors present an alternative suturing technique. They use
a 'C suture' to fix and minimize mobilization of the soft tissues around non
submerged implants.
PMID- 23153788
TI - Carotid cavernous fistula after surgically assisted rapid maxillary expansion
with a bone anchored appliance.
AB - Surgically assisted rapid maxillary expansion (SARME) is an effective and stable
method for treating severe maxillary transverse discrepancies in skeletally
mature individuals, but it has potential complications. The authors report the
case of a 34-year-old woman who developed carotid cavernous fistula after
undergoing SARME with a bone anchored appliance and discuss the possible
etiological basis of this condition.
PMID- 23153790
TI - Label-free quantitative proteomics trends for protein-protein interactions.
AB - Understanding protein interactions within the complexity of a living cell is
challenging, but techniques coupling affinity purification and mass spectrometry
have enabled important progress to be made in the past 15 years. As
identification of protein-protein interactions is becoming easier, the
quantification of the interaction dynamics is the next frontier. Several
quantitative mass spectrometric approaches have been developed to address this
issue that vary in their strengths and weaknesses. While isotopic labeling
approaches continue to contribute to the identification of regulated
interactions, techniques that do not require labeling are becoming increasingly
used in the field. Here, we describe the major types of label-free quantification
used in interaction proteomics, and discuss the relative merits of data dependent
and data independent acquisition approaches in label-free quantification. This
article is part of a Special Issue entitled: From protein structures to clinical
applications.
PMID- 23153789
TI - Usefulness of stereotactic biopsy and neuroimaging in management of HIV-1 Clade C
associated focal brain lesions with special focus on cerebral toxoplasmosis.
AB - BACKGROUND: Focal brain lesions (FBL) in HIV/AIDS frequently pose a diagnostic
dilemma as the etiology varies from infective (tuberculoma, toxoplasmosis and
tuberculous abscesses) to neoplastic lesions like lymphoma. For determining
etiology, advanced neuroimaging techniques, serological and molecular biological
tests have been evolved with varying sensitivities/specificities. Stereotactic
biopsy (STB) of the lesions is reserved for lesions unresponsive to appropriate
therapy. OBJECTIVE AND METHODS: In this study, the diagnostic yield of
neuroimaging [cranial CT (n=25), MRI (n=24), and Th201/99Tc SPECT scan (n=18)] is
compared with histopathological diagnosis obtained by STB (n=21) or autopsy (n=4)
in 25 HIV-1 subtype C seropositive individuals with FBL identified by
neuroimaging with special reference to cerebral toxoplasmosis in an eighteen
month study period (2006-2007). RESULTS AND CONCLUSION: Cerebral toxoplasmosis
was the most frequent cause of FBL (21/25, 84%), followed by one case each of
tuberculoma, progressive multifocal leukoencephalopathy (PML), primary central
nervous system lymphoma (PCNSL) and measles inclusion body encephalitis (MIBE),
the last two diagnosed at autopsy. Of the 21 cases of cerebral toxoplasmosis,
definitive diagnosis with histopathological confirmation was available in 14/21
(66.6%), with indirect evidence suggesting probable toxoplasmosis in seven, all
of whom responded to antitoxoplasma therapy. CT and MRI had comparable
specificities (75%), while MRI had marginally higher sensitivity (85% versus
80.9%) in detecting multiple lesions. The positive predictive value of both CT
and MRI was identical (94.4%), suggesting that CT maybe a cost effective
screening tool in resource restricted settings, for evaluating FBL. Sensitivity
of 99Tc SPECT scan for diagnosing inflammatory lesions was 75% but failed to
differentiate PCNSL from toxoplasmosis. This study is the first of its kind from
India analyzing FBL with specific focus on cerebral toxoplasmosis in the setting
of HIV-1 subtype C.
PMID- 23153791
TI - Change in protein content during seed germination of a high altitude plant
Podophyllum hexandrum Royle.
AB - Podophyllum hexandrum Royle (=Sinopodophyllum hexandrum) is a high-altitude
medicinal plant exploited for its etoposides which are potential anticancer
compounds. An effective, conventional propagation method is by seed. However,
seed germination is erratic, and seedling survival is low. A marginal increase in
Podophyllum seed germination was attained with organic solvents. In the present
study an attempt was made to decipher the physiological and biochemical barriers
in terms of change in proteins during seed germination of Podophyllum.
Comparative 2-DE analysis between un-germinated (dormant) and germinating seeds
revealed nearly 113 differentially expressed proteins, whereas Peptide Mass
Fingerprint (PMF) analysis of 97 protein spots revealed appearance of 27
proteins, up-accumulation of 11 proteins, down-accumulation of 19 proteins and
disappearance of 40 proteins with germination. Identified 59 proteins in the
homology search were involved in metabolism (carbohydrate and amino acid
metabolism; 20 proteins), ABA/GA signaling (17 proteins) and stress (15 proteins)
related proteins. Seven proteins were with unknown function. Two-DE, and MS/MS
analysis in conjunction with semi-quantitative RT-PCR data of cell wall
hydrolyzing genes, revealed that in Podophyllum the radicle protrusion occurs
might be because of the up-accumulation of cell wall hydrolases i.e. beta-1, 3
glucanase and XET which weakens the thick walled micropylar endosperm.
PMID- 23153793
TI - Improved proteomic profiling of the cell surface of culture-expanded human bone
marrow multipotent stromal cells.
AB - A comprehensive analysis of the membrane proteome is essential to explain the
biology of multipotent stromal cells and identify reliable protein biomarkers for
the isolation as well as tracking of cells during differentiation and maturation.
However, proteomic analysis of membrane proteins is challenging and they are
noticeably under-represented in numerous proteomic studies. Here we introduce new
approach, which includes high pressure-assisted membrane protein extraction,
protein fractionation by gel-eluted liquid fraction entrapment electrophoresis
(GELFREE), and combined use of liquid chromatography MALDI and ESI tandem mass
spectrometry. This report presents the first comprehensive proteomic analysis of
membrane proteome of undifferentiated and culture-expanded human bone marrow
multipotent stromal cells (hBM-MSC) obtained from different human donors. Gene
ontology mapping using the Ingenuity Pathway Analysis and DAVID programs revealed
the largest membrane proteomic dataset for hBM-MSC reported to date.
Collectively, the new workflow enabled us to identify at least two-fold more
membrane proteins compared to published results on hBM-MSC. A total of 84 CDs
were identified including 14 CDs identified for the first time. This dataset can
serve as a basis for further exploration of self-renewal, differentiation and
characterization of hBM-MSC.
PMID- 23153792
TI - Recent advances in cardiovascular proteomics.
AB - Cardiovascular diseases (CVDs) are the major source of global morbidity and death
and more people die annually from CVDs than from any other cause. These diseases
can occur quickly, as seen in acute myocardial infarction (AMI), or progress
slowly over years as with chronic heart failure. Advances in mass spectrometry
detection and analysis, together with improved isolation and enrichment
techniques allowing for the separation of organelles and membrane proteins, now
allow for the indepth analysis of the cardiac proteome. Here we outline current
insights that have been provided through cardiovascular proteomics, and discuss
studies that have developed innovative technologies which permit the examination
of the protein complement in specific organelles including exosomes and secreted
proteins. We highlight these foundational studies and illustrate how they are
providing the technologies and tools which are now being applied to further study
cardiovascular disease; provide new diagnostic markers and potentially new
methods of cardiac patient management with identification of novel drug targets.
This article is part of a Special Issue entitled: From protein structures to
clinical applications.
PMID- 23153794
TI - Whole-exome sequencing reveals recurrent somatic mutation networks in cancer.
AB - The second-generation sequencing technologies have been extensively used to
reveal the mechanism of tumorigenesis and find critical genes in cancer
progression that can be potential targets of clinic treatment. Exome is a part of
genome formed by exons which are the protein-coding portions of genes. The whole
exome sequencing information can reflect the mutations of the protein-coding
region in the genome and depict the causal relationship between the mutations and
phenotypes. Now, many network-based methods have been developed to identify
cancer driver modules or pathways, which not only provide new insights into
molecular mechanism of disease progression at network level but also can avoid
low coverage or lowly recurrent on disease samples in contrast to individual
driver genes. In this review, we focus on the recent advances on network-based
methods for identifying cancer driver modules or pathways, including methods of
whole-exome sequencing, somatic mutation detection, driver mutation
identification, and mutation network reconstruction.
PMID- 23153795
TI - Cytokines: how important are they in mediating sickness?
AB - Sickness refers to a set of coordinated physiological and behavioral changes in
response to systemic inflammation. It is characterized by fever, malaise, social
withdrawal, fatigue, and anorexia. While these responses collectively represent a
protective mechanism against infection and injury, increasing lines of evidence
indicate that over-exaggerated or persistent sickness can damage the brain, and
could possibly raise the risk to developing delirium. Therefore, a clear
understanding in sickness will be beneficial. It has long been believed that
sickness results from increased systemic cytokines occurring during systemic
inflammation. However, in recent years more and more conflicting data have
suggested that development of sickness following peripheral immune challenge
could be independent of cytokines. Hence, it is confusing as to whether cytokines
really do act as primary mediators of sickness, or if they are secondary to
alternative inducing factor(s). In this review, we will (1) introduce the
relationships between systemic inflammation, cytokines, sickness, and delirium,
and (2) attempt to interpret the recent controversies.
PMID- 23153796
TI - Multiple subregions in superior temporal cortex are differentially sensitive to
vocal expressions: a quantitative meta-analysis.
AB - Vocal expressions of emotions consistently activate regions in the superior
temporal cortex (STC), including regions in the primary and secondary auditory
cortex (AC). Studies usually report broadly extended functional activations in
response to vocal expressions, with considerable variation in peak locations
across several auditory subregions. This might suggest different and distributed
functional roles across these subregions instead of a uniform role for the
decoding of vocal emotions. We reviewed recent studies and conducted an
activation likelihood estimation meta-analysis summarizing recent fMRI and PET
studies dealing with the processing of vocal expressions in the STC and AC. We
included two stimulus-specific factors (paraverbal/nonverbal expression, stimulus
valence) and one task-specific factor (attentional focus) in the analysis. These
factors considerably influenced whether functional activity was located in the AC
or STC (influence of valence and attentional focus), the laterality of
activations (influence of paraverbal/nonverbal expressions), and the anterior
posterior location of STC activity (influence of valence). These data suggest
distributed functional roles and a differentiated network of auditory subregions
in response to vocal expressions.
PMID- 23153797
TI - Synthesis, characterization and biological studies of diosgenyl analogues.
AB - A series of optical amino acid diosgenyl esters and diosgenyl salicylate
conjugates were designed and synthesized to develop new anticancer and anti
inflammatory agents. The analogue 9c that contains an 6-aminohexanoic acid
residue at C-3 of diosgenin exhibits higher potency against all three tumor cell
lines with IC(50) values ranging from 4.7 MUM in C26 cells to 14.6 MUM in Hep G2
cells. In addition, seven of newly synthesized compounds significantly inhibit
xylene-induced ear edema and exhibit comparable or better anti-inflammatory
activities than those of diosgenin and aspirin. Furthermore, preliminary
structure-activity relationship studies demonstrate that diosgenyl salicylate
conjugates have stronger anti-inflammatory activities than amino acid diosgenyl
esters.
PMID- 23153799
TI - Spatial analysis of corresponding fingerprint features from match and close non
match populations.
AB - The development of statistical models for forensic fingerprint identification
purposes has been the subject of increasing research attention in recent years.
This can be partly seen as a response to a number of commentators who claim that
the scientific basis for fingerprint identification has not been adequately
demonstrated. In addition, key forensic identification bodies such as ENFSI [1]
and IAI [2] have recently endorsed and acknowledged the potential benefits of
using statistical models as an important tool in support of the fingerprint
identification process within the ACE-V framework. In this paper, we introduce a
new Likelihood Ratio (LR) model based on Support Vector Machines (SVMs) trained
with features discovered via morphometric and spatial analyses of corresponding
minutiae configurations for both match and close non-match populations often
found in AFIS candidate lists. Computed LR values are derived from a
probabilistic framework based on SVMs that discover the intrinsic spatial
differences of match and close non-match populations. Lastly, experimentation
performed on a set of over 120,000 publicly available fingerprint images (mostly
sourced from the National Institute of Standards and Technology (NIST) datasets)
and a distortion set of approximately 40,000 images, is presented, illustrating
that the proposed LR model is reliably guiding towards the right proposition in
the identification assessment of match and close non-match populations. Results
further indicate that the proposed model is a promising tool for fingerprint
practitioners to use for analysing the spatial consistency of corresponding
minutiae configurations.
PMID- 23153798
TI - Identification of novel series of pyrazole and indole-urea based DFG-out PYK2
inhibitors.
AB - Previous drug discovery efforts identified classical PYK2 kinase inhibitors such
as 2 and 3 that possess selectivity for PYK2 over its intra-family isoform FAK.
Efforts to identify more kinome-selective chemical matter that stabilize a DFG
out conformation of the enzyme are described herein. Two sub-series of PYK2
inhibitors, an indole carboxamide-urea and a pyrazole-urea have been identified
and found to have different binding interactions with the hinge region of PYK2.
These leads proved to be more selective than the original classical inhibitors.
PMID- 23153800
TI - Virtual anthropology: a comparison between the performance of conventional X-ray
and MDCT in investigating the trabecular structure of long bones.
AB - Recently, modern cross-sectional imaging techniques such as multi-detector
computed tomography (MDCT) have pioneered post mortem investigations, especially
in forensic medicine. Such approaches can also be used to investigate bones non
invasively for anthropological purposes. Long bones are often examined in
forensic cases because they are frequently discovered and transferred to medico
legal departments for investigation. To estimate their age, the trabecular
structure must be examined. This study aimed to compare the performance of MDCT
with conventional X-rays to investigate the trabecular structure of long bones.
Fifty-two dry bones (24 humeri and 28 femora) from anthropological collections
were first examined by conventional X-ray, and then by MDCT. Trabecular structure
was evaluated by seven observers (two experienced and five inexperienced in
anthropology) who analyzed images obtained by radiological methods. Analyses
contained the measurement of one quantitative parameter (caput diameter of
humerus and femur) and staging the trabecular structure of each bone. Preciseness
of each technique was indicated by describing areas of trabecular destruction and
particularities of the bones, such as pathological changes. Concerning
quantitative parameters, the measurements demonstrate comparable results for the
MDCT and conventional X-ray techniques. In contrast, the overall inter-observer
reliability of the staging was low with MDCT and conventional X-ray. Reliability
increased significantly when only the results of the staging performed by the two
experienced observers were compared, particularly regarding the MDCT analysis.
Our results also indicate that MDCT appears to be better suited to a detailed
examination of the trabecular structure. In our opinion, MDCT is an adequate tool
with which to examine the trabecular structure of long bones. However, adequate
methods should be developed or existing methods should be adapted to MDCT.
PMID- 23153801
TI - The role of micro-computed tomography in forensic investigations.
AB - The use of micro-CT within forensic practice remains an emerging technology,
principally due to its current limited availability to forensic practitioners.
This review provides those with little or no previous experience of the potential
roles of micro-CT in forensic practice with an illustrated overview of the
technology, and the areas of practice in which micro-CT can potentially be
applied to enhance forensic investigations.
PMID- 23153802
TI - Statistical evaluation of the influence of writing postures on on-line
signatures. Study of the impact of time.
AB - The aim of this study is to investigate the influence of unusual writing
positions on a person's signature, in comparison to a standard writing position.
Ten writers were asked to sign their signature six times, in each of four
different writing positions, including the standard one. In order to take into
consideration the effect of the day-to-day variation, this same process was
repeated over 12 sessions, giving a total of 288 signatures per subject. The
signatures were collected simultaneously in an off-line and on-line acquisition
mode, using an interactive tablet and a ballpoint pen. Unidimensional variables
(height to width ratio; time with or without in air displacement) and time
dependent variables (pressure; X and Y coordinates; altitude and azimuth angles)
were extracted from each signature. For the unidimensional variables, the
position effect was assessed through ANOVA and Dunnett contrast tests. Concerning
the time-dependent variables, the signatures were compared by using dynamic time
warping, and the position effect was evaluated through classification by linear
discriminant analysis. Both of these variables provided similar results: no
general tendency regarding the position factor could be highlighted. The
influence of the position factor varies according to the subject as well as the
variable studied. The impact of the session factor was shown to cover the impact
that could be ascribed to the writing position factor. Indeed, the day-to-day
variation has a greater effect than the position factor on the studied signature
variables. The results of this study suggest guidelines for best practice in the
area of signature comparisons and demonstrate the importance of a signature
collection procedure covering an adequate number of sampling sessions, with a
sufficient number of samples per session.
PMID- 23153803
TI - Karyotype polymorphism and chromosomal rearrangement in populations of the
phytopathogenic fungus, Ascochyta rabiei.
AB - The fungus Ascochyta rabiei is the causal agent of Ascochyta blight of chickpea
and the most serious threat to chickpea production. Little is currently known
about the genome size or organization of A. rabiei. Given recent genome
sequencing efforts, characterization of the genome at a population scale will
provide a framework for genome interpretation and direction of future
resequencing efforts. Electrophoretic karyotype profiles of 112 isolates from 21
countries revealed 12-16 chromosomes between 0.9 Mb and 4.6 Mb with an estimated
genome size of 23 Mb-34 Mb. Three general karyotype profiles A, B, and C were
defined by the arrangement of the largest chromosomes. Approximately one-third of
isolates (group A) possessed a chromosome larger than 4.0 Mb that was absent from
group B and C isolates. The ribosomal RNA gene (rDNA) cluster was assigned to the
largest chromosome in all except four isolates (group C) whose rDNA cluster was
located on the second largest chromosome (3.2 Mb). Analysis of progeny from an in
vitro sexual cross between two group B isolates revealed one of 16 progeny with
an rDNA-encoding chromosome larger than 4.0 Mb similar to group A isolates, even
though a chromosome of this size was not present in either parent. No expansion
of the rDNA cluster was detected in the progeny, indicating the increase in
chromosome size was not due to an expansion in number of rDNA repeats. The
karyotype of A. rabiei is relatively conserved when compared with published
examples of asexual ascomycetes, but labile with the potential for large scale
chromosomal rearrangements during meiosis. The results of this study will allow
for the targeted sequencing of specific isolates to determine the molecular
mechanisms of karyotype variation within this species.
PMID- 23153804
TI - Molecular phylogenetic analyses based on the nuclear rRNA genes and the intron
exon structures of the nuSSU rRNA gene in Dictyocatenulata alba (anamorphic
Ascomycota).
AB - Molecular phylogenies inferred from the nuclear small subunit rRNA gene (nuSSU),
nuclear large subunit rRNA gene D1/D2 region (nuLSU), and ITS-5.8S rRNA gene
(ITS) indicated that five cultures of the lichenized hyphomycete Dictyocatenulata
alba isolated from Japan form a monophyletic clade with high bootstrap support,
and a close relationship to the Ostropomycetidae (Lecanoromycetes,
Pezizomycotina, Ascomycota). Insertion sequences were found in the nuSSU of all
isolates [e.g., nine insertions in the strain JCM 5358 (Japan Collection of
Microorganisms)], some of which were group I introns. Five new insertion
positions were found among the D. alba isolates. Using BLAST, none of the
insertion sequences of D. alba were closely related to those of fungi or other
organisms deposited in public DNA databases. Insertion positions were similar in
some isolates, and two positions were common to all isolates. Although all
phylogenetic analyses based on nuSSU, nuLSU, and ITS revealed the monophyly of D.
alba, the isolates were divided into two (in the nuSSU tree) or three (in the
nuLSU and ITS trees) groups. Based on the phylogenetic analyses and the intron
exon structures, the five isolates identified as D. alba belong to three cryptic
species and therefore D. alba should be considered a species complex. The very
slow-growing, tough agar colonies of the isolates, the occurrence of the species
on both slightly lichenized and nonlichenized surfaces of trees, or pebbles
(rarely on soil), suggest that the members of the D. alba complex may be
lichenized. The photobiont was not clearly identified in this study.
PMID- 23153805
TI - Molecular phylogeny and phenotypic variability of clinical and environmental
strains of Aspergillus flavus.
AB - Aspergillus flavus is the second most common cause of aspergillosis infection in
immunocompromised patients and is responsible for the production of aflatoxins.
Little is known about the population structure of A. flavus, although recent
molecular and phenotypic data seem to demonstrate that different genetic lineages
exist within this species. The aim of this study was to carry out a
morphological, physiological, and molecular analysis of a set of clinical and
environmental isolates to determine whether this variability is due to species
divergence or intraspecific diversity, and to assess whether the clinical
isolates form a separate group. The amdS and omtA genes were more
phylogenetically informative than the other tested genes and their combined
analysis inferred three main clades, with no clear distinction between clinical
and environmental isolates. No important morphological and physiological
differences were found between the members of the different clades, with the
exception of the assimilation of d-glucosamine, which differentiates the members
of the clade II from the others.
PMID- 23153806
TI - Genome-wide identification and profiling of microRNA-like RNAs from Metarhizium
anisopliae during development.
AB - Metarhizium anisopliae is one of the most common species of entopathogenic fungi.
It has economic and social benefits in many countries where used in agriculture
as an important biological control agent of insect pests. M. anisopliae can exist
as multiple cell types, which suggests that this fungus has a complex way of gene
regulation. MicroRNAs (miRNAs) are endogenous small noncoding RNAs. They play a
crucial role in the regulation of gene expression and cell function in plants,
animals, and in fungi where they were termed miRNA-like RNAs (milRNAs). In this
study, we aimed to identify potential milRNAs in M. anisopliae that may regulate
the processes of mycelium growth and conidiogenesis (CO). Two small RNA (sRNA)
libraries were constructed and submitted to Solexa sequencing. Fifteen milRNAs
were identified using deep-sequencing and computational analysis; most of these
milRNAs originated from single genes. Database searches revealed that these novel
milRNAs had no homologues in other organisms and were, therefore, M. anisopliae
specific. Many of the milRNAs had differential expression profiles for either
mycelium growth or CO. The expression of the selected milRNAs was validated by
quantitative reverse transcription polymerase chain reaction. Seventy-eight
potential target mRNAs for 14 of the milRNAs were identified successfully by
computational analysis. These milRNAs may play an important role in the
regulation of mycelial growth and conidiation in M. anisopliae. To our knowledge,
this study is the first report of milRNA profiles of organisms in the order
Hypocreales. This information could be used to study the regulation of genes and
their networks in M. anisopliae.
PMID- 23153807
TI - Quantifying Hg within ectomycorrhizal fruiting bodies, from emergence to
senescence.
AB - Ectomycorrhizal fruiting bodies (basidiomata) collected from forested areas in
southwestern New Brunswick were analyzed for total mercury, sulphur, nitrogen,
and carbon concentrations (THg, TS, TN, and TC, respectively). This analysis was
done for caps and stalks and by development stage (emergent, mature, senescent)
across 27 species associated with five classes, eight families, and 13 genera.
Across the species, THg correlated positively with TN and TS, thereby implying N
as well as S mitigated transfer of Hg from the mycelia into the basidiomata, with
THg ranging from 3 to 10 457 ppb. TS, TN, and TC varied from 0.07 to 1, 1 to 11,
and 43 to 53 %, respectively. Cap and stalk THg, TS, TN, and TC were also
correlated to one another, with mean stalk/cap ratios of 0.59, 0.76, 0.71, and
0.98, respectively. Soil availability indexed by THg, TS, TN, and TC within the
forest floor contributed to basidiomatal THg as well. THg, THg/TS, and THg/N
varied strongly by species. These variations involved: (i) no growth dilution and
no volatilization (Group I), (ii) growth dilution only (Group II), (iii) growth
dilution followed by loss during senescence (Group III), and (iv) growth dilution
combined with loss from emergence onward (Group IV). Depending on species, TN and
TS remained the same or declined from 100 % at emergence to about 80 and 70 % at
senescence. Lack of THg decline for the Group I species would be due to HgS
encapsulation. Reanalyzing the freeze-dried samples revealed that THg continued
to drop during the first year of air-dry storage for the Group II, II, and IV
species, but TS, TN, and TC remained stable. The results were quantified by way
of best-fitted regression models.
PMID- 23153808
TI - Discovery of a fourth evolutionary lineage of Phytophthora ramorum: EU2.
AB - Phytophthora ramorum is a recently introduced, aggressive Phytophthora species
that has caused extensive mortality of oak and tanoak trees in the western USA
and Japanese larch trees in the UK. P. ramorum is also present on Rhododendron,
Camellia, and Viburnum in the nursery industry, which is thought to have been the
pathway for its spread into new geographic regions including forests and natural
ecosystems. Three lineages of P. ramorum have been described, informally
designated EU1, NA1, and NA2, and each lineage is believed to originate from an
as yet unknown exotic centre of origin. Preliminary SSR and sequence analysis of
isolates from a UK P. ramorum survey revealed seven isolates with profiles that
did not match the previously known lineages. Detailed SSR and multilocus sequence
analysis of these isolates are presented, allowing us to assign these isolates to
a new P. ramorum lineage, designated EU2. Although the known geographical origin
of these isolates is currently limited to Northern Ireland and western Scotland,
the EU2 lineage isolates have been obtained from four different host plants,
including Japanese larch. All isolates are of A1 compatibility type, which
implies that this finding does not increase the risk of outcrossing with the EU1
lineage isolates already present in the UK. The oldest EU2 strain was isolated in
2007 but no SSR-based intraEU2 lineage genotypic diversity was detected. The
combination of these elements points to a recent introduction, despite emergency
phytosanitary measures to control introduction and spread. A PCR-RFLP method for
the rapid identification of EU2 lineage isolates is presented.
PMID- 23153809
TI - Multiple-scale environmental modulation of lichen reproduction.
AB - It is necessary to understand how environmental changes affect plant fitness to
predict survival of a species, but this knowledge is scarce for lichens and
complicated by their formation of sexual and asexual reproductive structures. Are
the presence and number of reproductive structures in Lobaria pulmonaria, a
threatened lichen, dependent on thallus size, and is their formation sequential?
Does any size-dependence and sequential formation vary along a climate gradient?
Generalized linear mixed models were used to explore the effect of environmental
predictors on the size and presence/abundance of each reproductive structure and
to determine the probability of a given-sized thallus to develop any reproductive
structure. The largest individuals are more likely to develop reproductive
structures, and the lichen uses a mixed strategy of early asexual reproduction
and late sexual. Macro and microclimatic variables also influenced reproductive
capacity. Relationships among climate conditions and lichen size and reproductive
capacity can compromise the future viability of the species in the most southern
populations of Europe.
PMID- 23153810
TI - Lignopurines: a new family of hybrids between cyclolignans and purines. Synthesis
and biological evaluation.
AB - A new family of hybrids between cyclolignans related to podophyllic aldehyde, a
non-lactonic cyclolignan, and purines were prepared and evaluated against several
human tumour cell lines. Both fragments, cyclolignan and purine, were linked
through aliphatic and aromatic chains. The influence on the cytotoxicity of the
purine substitution and the nature of the linker is analyzed. The new family was
slightly less cytotoxic than the parent podophyllic aldehyde, although the
selectivity is maintained or even improved and among the linkers used, the
presence of an aromatic ring gave the most potent and selective derivatives
within the new series tested. Cell cycle and confocal studies demonstrate that
these derivatives interfere with the tubulin polymerization and arrest cells at
the G(2)/M phase, in the same way than the parent compounds podophyllotoxin and
podophyllic aldehyde do.
PMID- 23153811
TI - Hesperetin: an inhibitor of the transforming growth factor-beta (TGF-beta)
signaling pathway.
AB - We have identified a previously unknown function of the natural compound,
hesperetin. Here, we demonstrate that this small molecular agent is able to
inhibit the transforming growth factor-beta (TGF-beta) signaling pathway. Single
molecule force measurements and single-molecule fluorescence imaging show that
hesperetin interferes with ligand-receptor interactions. Furthermore, by Western
blot analysis, it was confirmed that hesperetin also inhibits the phosphorylation
of Smad3, a down-stream target of the TGF-beta pathway. In addition we
demonstrated that this compound hinders TGF-beta1-induced cancer cell migration
and invasion. These results suggest a potential future application for hesperetin
as a TGF-beta inhibitor in cancer therapy.
PMID- 23153812
TI - Recent advances in the development of selective human MAO-B inhibitors:
(hetero)arylidene-(4-substituted-thiazol-2-yl)hydrazines.
AB - A large series of (4-substituted-thiazol-2-yl)hydrazine derivatives was
synthesized in good yield and assayed for their in vitro human monoamine oxidase
(hMAO) inhibitory activity and selectivity. Most of them showed inhibitory
activity in the nanomolar range and hMAO-B selective inhibition higher than
reference drugs, demonstrating our interest in this privileged scaffold. The
structure-activity relationship of the different rings on the N1-hydrazine
position indicated that a pyridine ring was preferred with the presence of
electron-withdrawing substituents on the aryl group at C4 of the thiazole
nucleus. The substituent on the alpha-carbon to the N1-hydrazine moiety (methyl
or hydrogen) had a great influence on the activity and hMAO-B selectivity.
Moreover, the reversibility of the enzyme inhibition for the best active compound
was reported.
PMID- 23153813
TI - Synthesis and antiproliferative activity of helonioside A, 3',4',6'-tri-O
feruloylsucrose, lapathoside C and their analogs.
AB - The first total synthesis of natural phenylpropanoid sucrose esters (PSEs)
helonioside A 1, 3',4',6'-tri-O-feruloylsucrose 2 and lapathoside C 3 along with
17 unnatural PSE analogs has been successfully accomplished in a short and simple
synthetic route. A selected set of 17 synthesized PSEs were evaluated for the
antiproliferative activity against human cervical epithelioid carcinoma (HeLa)
cell lines using MTS assay method. Eleven (11) compounds showed significant
antiproliferative activity with their IC(50)values ranging from 0.16 to 6.01 MUM.
The structure-activity-relationship studies revealed that the antiproliferative
activity is influenced by the lipophilicity and number of feruloyl substituents
on these compounds. The preliminary screening indicated that these compounds are
potentially very valuable source for new lead chemotherapeutics.
PMID- 23153814
TI - Application of a post-docking procedure based on MM-PBSA and MM-GBSA on single
and multiple protein conformations.
AB - In the last decades, molecular docking has emerged as an increasingly useful tool
in the modern drug discovery process, but it still needs to overcome many hurdles
and limitations such as how to account for protein flexibility and poor scoring
function performance. For this reason, it has been recognized that in many cases
docking results need to be post-processed to achieve a significant agreement with
experimental activities. In this study, we have evaluated the performance of MM
PBSA and MM-GBSA scoring functions, implemented in our post-docking procedure
BEAR, in rescoring docking solutions. For the first time, the performance of this
post-docking procedure has been evaluated on six different biological targets
(namely estrogen receptor, thymidine kinase, factor Xa, adenosine deaminase,
aldose reductase, and enoyl ACP reductase) by using i) both a single and a
multiple protein conformation approach, and ii) two different software, namely
AutoDock and LibDock. The assessment has been based on two of the most important
criteria for the evaluation of docking methods, i.e., the ability of known
ligands to enrich the top positions of a ranked database with respect to
molecular decoys, and the consistency of the docking poses with crystallographic
binding modes. We found that, in many cases, MM-PBSA and MM-GBSA are able to
yield higher enrichment factors compared to those obtained with the docking
scoring functions alone. However, for only a minority of the cases, the
enrichment factors obtained by using multiple protein conformations were higher
than those obtained by using only one protein conformation.
PMID- 23153815
TI - Analysis of the discriminative inhibition of mammalian digestive lipases by 3
phenyl substituted 1,3,4-oxadiazol-2(3H)-ones.
AB - We report here the reactivity and selectivity of three 5-Methoxy-N-3-Phenyl
substituted-1,3,4-Oxadiazol-2(3H)-ones (MPOX, as well as meta and para
PhenoxyPhenyl derivatives, i.e.MmPPOX and MpPPOX) with respect to the inhibition
of mammalian digestive lipases: dog gastric lipase (DGL), human (HPL) and porcine
(PPL) pancreatic lipases, human (HPLRP2) and guinea pig (GPLRP2) pancreatic
lipase-related proteins 2, human pancreatic carboxyl ester hydrolase (hCEH), and
porcine pancreatic extracts (PPE). All three oxadiazolones displayed similar
inhibitory activities on DGL, PLRP2s and hCEH than the FDA-approved anti-obesity
drug Orlistat towards the same enzymes. These compounds appeared however to be
discriminative of HPL (poorly inhibited) and PPL (fully inhibited). The
inhibitory activities obtained experimentally in vitro were further rationalized
using in silico molecular docking. In the case of DGL, we demonstrated that the
phenoxy group plays a key role in specific molecular interactions within the
lipase's active site. The absence of this group in the case of MPOX, as well as
its connectivity to the neighbouring aromatic ring in the case of MmPPOX and
MpPPOX, strongly impacts the inhibitory efficiency of these oxadiazolones and
leads to a significant gain in selectivity towards the lipases tested. The
powerful inhibition of PPL, DGL, PLRP2s, hCEH and to a lesser extend HPL,
suggests that oxadiazolone derivatives could also provide useful leads for the
development of novel and more discriminative inhibitors of digestive lipases.
These inhibitors could be used for a better understanding of individual lipase
function as well as for drug development aiming at the regulation of the whole
gastrointestinal lipolysis process.
PMID- 23153816
TI - Synthesis of novel 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-thiones and
evaluation of their biocidal effects.
AB - Novel 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-thiones have been
synthesized in high yields by treatment of the corresponding oxo analogs with
Lawesson's reagent. The structure has been confirmed by X-ray analysis. The
compounds were tested for in vitro antifungal activity against Rhizoctonia
bataticola, Sclerotium rolfsii, Fusarium oxysporum and Alternaria porii. The
compounds exhibited moderate to good activity against all pathogens. Insecticidal
activity of these compounds against Spodoptera litura was observed to be
comparable to commercial pyrethroid insecticide, cypermethrin. The urease
inhibitory activity has also been studied.
PMID- 23153817
TI - Vascular access strategy for delivering long-term antimicrobials to patients with
infective endocarditis: device type, risk of infection and mortality.
AB - BACKGROUND: This paper reports the use of different vascular access devices and
the incidence of intravascular catheter-related infection (CRI) in patients
receiving intravenous antibiotics for infective endocarditis (IE). AIM: To
examine whether rates of infection vary with type of vascular access device, and
assess the impact of CRI on mortality in IE. METHODS: A prospective observational
service evaluation of all inpatients who received intravenous antibiotics for IE
was performed. In total, 114 inpatients were evaluated. All cases of CRI
[including exit-site infection, intravascular catheter-related bloodstream
infection (CRBSI) and mortality] were recorded. Tunnelled and non-tunnelled
central venous catheters (CVCs), and peripherally inserted cannulae were used for
antibiotic delivery. FINDINGS: There were 15 episodes of CRI, 11 of which were
CRBSI (all associated with CVC use). The remainder comprised uncomplicated exit
site infections. Use of tunnelled CVCs [hazard ratio (HR) 16.95, 95% confidence
interval (CI) 2.13-134.93; P = 0.007] and non-tunnelled CVCs (HR 24.54, 95% CI
2.83-212.55; P = 0.004) was associated with a significantly increased risk of
CRI. Risk of mortality increased significantly with Staphylococcus aureus as the
cause of IE (P < 0.001) and CRBSI (P = 0.034). CONCLUSION: Risk of CRI in
patients with IE is linked to the type of vascular access device used. Rates of
CRBSI were greatest with CVCs, while peripheral venous cannulae were not
associated with CRBSI or serious sequelae. Many patients (40%) tolerated complete
treatment courses delivered via peripheral cannulae. These findings confirm the
importance of device selection in reducing the risk of CRI; a potentially
modifiable variable that impacts on outcome and mortality in IE.
PMID- 23153818
TI - Haploinsufficiency of the autism candidate gene Neurobeachin induces autism-like
behaviors and affects cellular and molecular processes of synaptic plasticity in
mice.
AB - Neurobeachin (NBEA), a brain-enriched multidomain scaffolding protein involved in
neurotransmitter release and synaptic functioning, has been identified as a
candidate gene for autism spectrum disorder (ASD) in four unrelated patients
haploinsufficient for NBEA. The aim of this study was to map the behavioral
phenotype of Nbea(+/-) mice in order to understand its contribution to the
pathogenesis of ASD. ASD-like behavioral variables of Nbea(+/-) mice were related
to basal neuronal activity in different brain regions by in situ hybridizations
and extracellular field recordings of synaptic plasticity in hippocampal cornu
ammonis 1 (CA1) region. Levels of BDNF and phosphorylated cAMP response element
binding protein (CREB) were measured in an attempt to investigate putatively
underlying changes in these neuromolecules. Nbea(+/-) mice exhibit several ASD
like features, including changes in self-grooming behavior, social behaviors,
conditioned fear responses, and spatial learning and memory, which coincided with
enhanced long-term potentiation (LTP) in their CA1 region. The observed
alterations in learning and memory and hippocampal LTP are concomitant with
decreased expression of the immediate early gene zif268 in dorsomedial striatum
and hippocampal CA1 region, increased CREB phosphorylation, and increased
hippocampal BDNF expression. These findings indicate that Nbea haploinsufficiency
leads to various molecular and cellular changes that affect neuroplasticity and
behavioral functions in mice, and could thus underlie the ASD symptomatology in
NBEA deficient humans.
PMID- 23153819
TI - A novel human enterovirus C (EV-C118) identified in two children hospitalised
because of acute otitis media and community-acquired pneumonia in Israel.
AB - We report the discovery of a novel enterovirus C (EV-C118) identified in two
Israeli children hospitalised for acute otitis media and community-acquired
pneumonia. The highest pair-wise sequence identity scores with the EV-C109 and EV
C117 reference strains were, respectively, 63.5% and 63.6% nucleotide identity,
and 82.5% and 79.9% amino acid identity.
PMID- 23153820
TI - The value of CMV IgG avidity and immunoblot for timing the onset of primary CMV
infection in pregnancy.
AB - BACKGROUND: Primary CMV infections in pregnancy are usually asymptomatic and only
detected by serology. Estimating the onset of infection is a major diagnostic
goal, since primary infections around conception and in early gestation hold a
higher risk for congenital disease than those in later pregnancy. OBJECTIVES: To
assess the ability of serological supplementary CMV assays to date the onset of
primary infection. STUDY DESIGN: From our routine diagnosis we identified 61
pregnant women (n=188 serum samples) with precisely determined onset of CMV
primary infection either by IgG seroconversion (n=24) or by significant IgG
antibody rise (n=37). One hundred and forty-seven sera were investigated using
the VIDAS((r)) CMV IgG avidity EIA (BioMerieux) and 83 sera using the recomBlot
CMV IgG with avidity (Mikrogen). RESULTS: Both assays proofed to be reliable in
terms of timing the onset of CMV primary infection. An avidity index (AI) in the
VIDAS avidity EIA of <40% indicated primary infection within the last 20 weeks
(positive predictive value 93.4%; 99/106), whereas an intermediate AI excluded
primary infection within the last 12 weeks (negative predictive value 88.2%;
15/17). The recomBlot showed high reliability (PPV 96.9%; 31/33) for timing the
onset of infection within the last 14 weeks. Avidity testing by blot however
could not be interpreted in 11 of 47 sera (23.4%). CONCLUSION: For timing the
onset of infection (before or in early pregnancy) CMV avidity testing is most
helpful if carried out within the first trimester up to the beginning of second
trimester.
PMID- 23153822
TI - Apportioning global and non-global components of mercury deposition through
(210)Pb indexing.
AB - Our previous work has documented a correlation between Hg concentrations and
(210)Pb activity measured in wet deposition that might be used to help apportion
sources of Hg in precipitation. Here we present the results of a 27-month
precipitation collection effort using co-located samplers for Hg and (210)Pb
designed to assess this hypothesis. Study sites were located on the east and west
coasts of North America, in the continental interior, and on the Florida
Peninsula. Relatively high variability in Hg/(210)Pb ratios was found at all
sites regionally and seasonally (e.g., overall: 0.99-9.13ngdpm(-1)). The ratio of
average volume-weighted Hg concentrations and (210)Pb activities showed
consistent trends (higher in impacted area), with Glacier Bay in southeast
Alaska, exhibiting the lowest value. Assuming that Glacier Bay represents a
benchmark for a site with no regional contribution, we estimate less than 50% of
the Hg input was "global" at the Seattle and Florida sites. Differences in
Hg/(210)Pb in wet deposition could be due to either a regional/local source
contribution of Hg, or a regional/local enhancement in the removal of Hg from the
atmosphere (i.e., oxidants), however, this approach is not capable of discerning
between these two possibilities. Thus, this method of source apportionment
represents an estimate of the maximal amount of Hg contributed by regional
sources and may be limited in regions of deep convective mixing.
PMID- 23153821
TI - A norovirus outbreak in a nursing home: norovirus shedding time associated with
age.
AB - BACKGROUND: Norovirus (NoV) GII.4 has been identified as predominant in outbreaks
in the long-term health-care facilities. OBJECTIVES: NoV excretion during an
outbreak of gastroenteritis affecting 19/42 residents and 12/33 employees was
investigated in a Taiwan nursing home. STUDY DESIGN: Real-time reverse
transcription polymerase chain reaction (RT-PCR) was used to quantify viral RNA
from stool samples up to the point of negative detection. RESULTS: Initial fecal
viral loads in affected residents were higher than in affected employees
(p=0.024). Viral reduced rate was measured as 0.66/day, with a viral half-life of
1.7 days. A mixed model indicated that time (days post-illness onset), initial
virus load and resident status (as opposed to employee status) were the most
important determining factors of fecal NoV concentration. According to a
univariable accelerated failure time (AFT) model, strong associations existed
between virus excretion duration and both age (p=0.005) and resident status
(p=0.004). No associations were noted between viral excretion duration and either
initial viral load or diarrhea duration. According to a multivariable AFT model,
age was the only factor affecting virus excretion duration. CONCLUSION: In
conclusion, outbreaks in nursing homes may have resulted from environmental
contamination, the existence of asymptomatic residents and prolonged virus
shedding time in the elderly and care providers. This outbreak finished quickly
because frequent cleaning of the surface was done and contact precautions were
taken for prolonged viral shedding residents.
PMID- 23153823
TI - In vitro diagnosis of the first case of amitraz resistance in Rhipicephalus
microplus in Santo Tome (Corrientes), Argentina.
AB - In Argentina, the cattle tick Rhipicephalus microplus has already developed
resistance to organophosphates and synthetic pyrethroids. However, no cases of
amitraz resistance have ever been recorded in this country despite its heavy use.
A recent failure of amitraz to control ticks in a farm located in Santo Tome,
province of Corrientes, resulted in the collection of samples for acaricide
resistance diagnosis. The modified Drummond adult immersion test (AIT) and the
larval tarsal test (LTT) were performed separately in Argentina and Switzerland
to evaluate efficacy of amitraz and other acaricides. The AIT showed that
oviposition in the Santo Tome field isolate was not inhibited when it was
challenged to 250 and 500 ppm amitraz, and 50 ppm deltamethrin. However,
oviposition was reduced by 90.6% when this field isolate was challenged to a
combination of 400 ppm ethion and 100 ppm cypermethrin. To confirm the results
obtained with the AIT, 2 additional tick samples were collected and shipped to
Switzerland for resistance diagnosis of amitraz, cypermethrin and flumethrin,
using the LTT. With this bioassay, the resistance ratios of the 2 field isolates
were 32.5 and 57.0 for amitraz and between 5.9 and 27.2 for the synthetic
pyrethroids. Both in vitro bioassays confirmed amitraz and synthetic pyrethroid
resistance in the Santo Tome samples. These results account for the first
evidence of amitraz resistance in R. microplus in Argentina.
PMID- 23153824
TI - Canine visceral leishmaniasis: a comparative study of real-time PCR, conventional
PCR, and direct agglutination on sera for the detection of Leishmania infantum
infection.
AB - Canine visceral leishmaniasis (CVL) is endemic in northwestern Iran. This study
aimed to compare real-time PCR, conventional PCR, and the direct agglutination
test (DAT) for the diagnosis Leishmania infantum infection in 167 serum samples
of domestic dog. Bone marrow was used for parasitological examination (smears
and/or culture) in symptomatic visceral leishmaniasis, and serum was used for
detection of L. infantum kinetoplast DNA (kDNA) by both conventional PCR and real
time PCR, while anti-L. infantum antibodies in sera were measured by DAT. The
sera were collected from 37 symptomatic and 112 asymptomatic dogs during April to
May 2011. Eighteen presumed negative samples were obtained from healthy dogs kept
in non-endemic areas with no history of CVL and used as controls. All 18 samples
were negative by DAT and Dipstick rK39. DAT confirmed previous exposure to L.
infantum for all 149 serum samples collected from symptomatic and asymptomatic
dogs in CVL endemic areas of Iran. Among the 37 symptomatic dogs, 20 (54%), 25
(67.6%), 36 (97.3%), and 37 (100%) showed L. infantum infection by
parasitological methods, conventional PCR, real-time PCR, and DAT (>= 1:80),
respectively. Of 112 asymptomatic dogs, 79 (70.5%), 111 (99.1%), and 112 (100%)
were shown to be positive by conventional PCR, and DAT (>= 1:80), respectively.
For ethical reasons, no asymptomatic or healthy control dogs were examined by
parasitological methods. Three (16.7%) control dogs were positive by real-time
PCR, but were negative by DAT, dipstick rK39, and conventional PCR methods.
Parasitemia levels were measured by real-time PCR targeting kDNA using SYBR((r))
green assay. This quantitative technique detected infection in 89.9% (150/167) of
the domestic dogs that harbored L. infantum kDNA, ranging from 0.01 49 to 310.1
parasites/ml. The average was 16.60 parasites/ml. A good agreement (0.97) was
found between real-time PCR and DAT at >= 1:80 titer, used as cut-off value by
Kappa analysis. Thus, real-time PCR as a quantitative PCR assay on serum samples
represents a valuable tool for initial diagnosis of CVL when whole blood is not
available.
PMID- 23153825
TI - Expression of autism spectrum and schizophrenia in patients with a 22q11.2
deletion.
AB - BACKGROUND: Copy number variants (CNVs) associated with neuropsychiatric
disorders are increasingly being identified. While the initial reports were
relatively specific, i.e. implicating vulnerability for a particular
neuropsychiatric disorder, subsequent studies suggested that most of these CNVs
can increase the risk for more than one neuropsychiatric disorder. Possibly, the
different neuropsychiatric phenotypes associated with a single genetic variant
are really distinct phenomena, indicating pleiotropy. Alternatively, seemingly
different disorders could represent the same phenotype observed at different
developmental stages or the same underlying pathogenesis with different
phenotypic expressions. AIMS: To examine the relation between autism and
schizophrenia in patients sharing the same CNV. METHOD: We interviewed parents of
78 adult patients with the 22q11.2 deletion (22q11.2DS) to examine if autistic
symptoms during childhood were associated with psychosis in adulthood. We used
Chi-square, T-tests and logistic regression while entering cognitive level,
gender and age as covariates. RESULTS: The subgroup of 22q11.2DS patients with
probable ASD during childhood did not show an increased risk for psychosis in
adulthood. The average SRS scores were highly similar between those with and
those without schizophrenia. CONCLUSIONS: ASD and schizophrenia associated with
22q11.2DS should be regarded as two unrelated, distinct phenotypic
manifestations, consistent with true neuropsychiatric pleiotropy. 22q11.2DS can
serve as a model to examine the mechanisms associated with neuropsychiatric
pleiotropy associated with other CNVs.
PMID- 23153827
TI - Mirror neurons (and beyond) in the macaque brain: an overview of 20 years of
research.
AB - Mirror neurons are a class of neurons in the ventral pre-motor cortex (area F5)
and inferior parietal lobule (area PFG) that respond during the execution as well
as the observation of goal-directed motor acts. These intriguing response
properties stirred an intense debate in the scientific community with respect to
the possible cognitive role of mirror neurons. The aim of the present review is
to contribute to this debate by providing, in a single paper, an extended summary
of 20 years of neurophysiological research on mirror neurons in the macaque. To
this end, I provide a comprehensive description of the methodology and the main
results of each paper about mirror neurons published since their first report in
1992. Particular care was devoted in reporting the different response
characteristics and the percentages of neurons exhibiting them in relation to the
total number of studied neurons. Furthermore, I also discuss recent results
indicating that mirror neurons might not be confined to areas F5 and PFG and that
"mirroring" might not be limited to action observation. Finally, I offer a
unifying framework for many of the results discussed here by speculating that a
potential functional role of mirror neurons might be, during action observation,
to generalize from the particular grasping movement being observed to the
"concept" of grasping.
PMID- 23153828
TI - Deletion of Crry, the murine ortholog of the sporadic Alzheimer's disease risk
gene CR1, impacts tau phosphorylation and brain CFH.
AB - Large-scale genome-wide SNP association studies have identified an association
between variants of CR1, the gene encoding complement component receptor 1, and
the sporadic form of Alzheimer's disease. The role of CR1 and the complement
system in Alzheimer's disease remains far from clear. In rodents the closest
ortholog of CR1 is the Crry gene (Cr1-related protein Y). To begin to explore its
role in Alzheimer's disease we examined hippocampal lysates from Crry(-/-) mice
and age matched controls by immunoblotting. We measured complement factor H, a
component of the complement system and biomarker for Alzheimer's disease
progression, and tau phosphorylation at the serine 235 site, hyperphosphorylated
forms of tau being a defining neuropathological hallmark of the disease. We found
that levels of CFH and of tau phosphorylation at serine 235 were strongly and
significantly reduced in Crry(-/-) samples. These observations provide a starting
point for further attempts to determine the role of CR1 in the neuropathological
process driving Alzheimer's disease.
PMID- 23153829
TI - Treadmill running and static stretching improve long-lasting hyperalgesia, joint
limitation, and muscle atrophy induced by cast immobilization in rats.
AB - The effects of exercise on chronic pain induced by immobilization are
incompletely understood. The purpose of this study was to investigate whether
30min of treadmill running (TR; active exercise) and 10min of static stretching
(SS; passive exercise) of the immobilized hindlimb reduce widespread chronic
pain, joint limitation, and hindlimb muscle atrophy induced by cast
immobilization in rats. One hindlimb of Sprague Dawley (SD) rats was immobilized
for 2 weeks with a cast, and remobilization was conducted for 7 weeks. MRI study
showed that cast immobilization had induced inflammatory changes in the
immobilized hindlimb, beginning as early as 2h after cast removal; these changes
continued for 2-3 days. Mechanical hyperalgesia in the calf and hindpaw developed
as early as 2h after cast removal and continued for 7 weeks. TR and SS were
initiated 3 days after cast removal and were continued 3 times per week for 2
weeks. Both forms of exercise significantly inhibited mechanical hyperalgesia in
the calf and hindpaw in immobilized rats. Range-of-motion limitations in the knee
and ankle joints and calf muscle atrophy after cast removal were also decreased
by both TR and SS. This study is the first to demonstrate the beneficial effect
of TR and SS on widespread chronic pain, joint limitation, and muscle atrophy in
a cast-immobilized rat model.
PMID- 23153830
TI - An in vitro comparison study: the effects of fetal bovine serum concentration on
retinal progenitor cell multipotentiality.
AB - Retinal progenitor cells (RPCs) are an excellent resource for retinal replacement
therapy, because they show enormous potential to differentiate into retinal
specific cell types. While the differentiating influence of serum has long been
appreciated, the effects of serum concentration on RPC differentiation into
specified retinal neural cells have not been investigated. Using cultured murine
RPCs, this study compared the effects of different levels of fetal bovine serum
(FBS) (1%, 5%, 10% and 20%) on RPC differentiation in vitro. RPC
multipotentiality was assessed by using quantitative polymerase chain reaction
(qPCR) to determine the relative expression levels of 10 genes involved in
retinal development. In addition, analyses of cell morphology and retinal
development-related protein expression were performed using microscopy and
immunocytochemistry. The data revealed that 1% FBS-induced cultures
preferentially generated rhodopsin- and PKC-alpha-positive cells. Calbindin and
AP2alpha expression levels were greater in 5% FBS-induced cultures. Brn3a was
expressed at similar levels in 1%, 5% and 10% FBS treatment conditions but
diminished in 20% FBS conditions. Twenty percent FBS induced more glial
fibrillary acid protein (GFAP)-immunoreactive cells corresponding to glia
populations. These findings suggest that the concentration of FBS plays an
important role in RPC differentiation in vitro. Treatment with low levels of FBS
favors differentiation of rhodopsin-positive photoreceptors, interneurons and
retinal ganglion cells (RGCs), while high FBS concentrations preferentially
induce differentiation of glia cells. These results are expected to facilitate
research in the treatment of neurodegenerative retinal diseases.
PMID- 23153831
TI - [Which information is given to ALS patients carrying the pathogenic
hexanucleotide repeat expansion of c9orf72?].
PMID- 23153832
TI - [Foreword].
PMID- 23153826
TI - Dysregulation of RNA polymerase I transcription during disease.
AB - Transcription of the ribosomal RNA genes by the dedicated RNA polymerase I enzyme
and subsequent processing of the ribosomal RNA are fundamental control steps in
the synthesis of functional ribosomes. Dysregulation of Pol I transcription and
ribosome biogenesis is linked to the etiology of a broad range of human diseases.
Diseases caused by loss of function mutations in the molecular constituents of
the ribosome, or factors intimately associated with RNA polymerase I
transcription and processing are collectively termed ribosomopathies.
Ribosomopathies are generally rare and treatment options are extremely limited
tending to be more palliative than curative. Other more common diseases are
associated with profound changes in cellular growth such as cardiac hypertrophy,
atrophy or cancer. In contrast to ribosomopathies, altered RNA polymerase I
transcriptional activity in these diseases largely results from dysregulated
upstream oncogenic pathways or by direct modulation by oncogenes or tumor
suppressors at the level of the RNA polymerase I transcription apparatus itself.
Ribosomopathies associated with mutations in ribosomal proteins and ribosomal RNA
processing or assembly factors have been covered by recent excellent reviews. In
contrast, here we review our current knowledge of human diseases specifically
associated with dysregulation of RNA polymerase I transcription and its
associated regulatory apparatus, including some cases where this dysregulation is
directly causative in disease. We will also provide insight into and discussion
of possible therapeutic approaches to treat patients with dysregulated RNA
polymerase I transcription. This article is part of a Special Issue entitled:
Transcription by Odd Pols.
PMID- 23153833
TI - [Acute hemolytic anemia in an HIV patient after inhalation of amyl nitrite].
PMID- 23153834
TI - Traditional Chinese herbal medicine as a source of molecules with antiviral
activity.
AB - Traditional Chinese herbal medicine (TCHM) is widely used in the prevention and
treatment of viral infectious diseases. However, the operative mechanisms of TCHM
remain largely obscure, mainly because of its complicated nature and the
fragmented nature of research. In recent years, systematic methodologies have
been developed to discover the active compounds in TCHM and to elucidate its
underlying mechanisms. In this review, we summarize recent progress in TCHM-based
antiviral research in China and other Asian countries. In particular, this review
focuses on progress in targeting key steps in the viral replication cycle and key
cellular components of the host defense system. Recent developments in
centralized and standardized TCHM screening and databases are also summarized.
PMID- 23153835
TI - Gait variability and disability in multiple sclerosis.
AB - Gait variability is clinically relevant in some populations, but there is limited
documentation of gait variability in persons with multiple sclerosis (MS). This
investigation examined average and variability of spatiotemporal gait parameters
in persons with MS and healthy controls and subsequent associations with
disability status. 88 individuals with MS (age 52.4+/-11.1) and 20 healthy
controls (age 50.9+/-8.7) performed two self-paced walking trials on a 7.9-m
electronic walkway to determine gait parameters. Disability was indexed by the
Expanded Disability Status Scale (EDSS) and ranged between 2.5 and 6.5. Gait
variability was indexed by standard deviation (SD) and coefficient of variation
(CV=SD/mean) of step time, step length, and step width. Average gait parameters
were significantly correlated with EDSS (rho=0.756-0.609) and were significantly
different in individuals with MS compared to controls (p<=0.002). Also, step
length (p<0.001) and step time (p<0.001) variability were both significantly
greater in MS compared to controls. EDSS was positively correlated with step
length variability and individuals with MS who used assistive devices to walk had
significantly greater step length variability than those who walked independently
(p's<.05). EDSS was correlated with step time and length variability even when
age was taken into account. Additionally, Fisher's z test of partial correlations
revealed that average gait parameters were more closely related to disability
status than gait variability in individuals with MS. This suggests that focusing
on average gait parameters may be more important than variability in therapeutic
interventions in MS.
PMID- 23153836
TI - The assessment of cervical sensory motor control: a systematic review focusing on
measuring methods and their clinimetric characteristics.
AB - BACKGROUND: Cervical sensorimotor control (CSMC) becomes increasingly important
in the assessment and treatment of patients with neck pain. This review aims to
compare commonly used CSMC measuring methods in terms of required tasks,
measuring device and clinimetric properties. SEARCH METHODS: A systematic review
of two databases, followed by methodological quality assessment (CBO guidelines).
RESULTS: The methodological quality of 34 included articles was generally good
(five to seven out of eight), the inter-rater agreement was excellent
(kappaw=0.966, p<0.01). Following tasks were found: head repositioning accuracy
to the neutral head position (HRA-to-NHP) and to a target position (HRA-to
target), a virtual reality test, a continuous linear movement technique (CLMT)
and an object following non-linear movement technique (NLMT) (The FlyTM). Test
retest reliability was fair to excellent (ICC 0.35-0.87) for the HRA-to-NHP, very
bad to excellent (ICC 0.01-0.90) for the HRA-to-target, fair to good (ICC 0.25
0.77) for the virtual reality test and moderate to excellent (ICC: 0.60-0.86) for
The FlyTM. The reliability of the CLMT was not documented. The HRA-to-NHP, The
FlyTM and the CLMT can discriminate between patients with neck complaints and
controls (discriminant validity). Currently, only The FlyTM can discriminate
between different patient populations (post-traumatic and non-traumatic neck
pain). The sensitivity, specificity and responsiveness of the methods have to be
assessed in future research. CONCLUSIONS: The dynamic method The FlyTM appears to
be more reliable than the HRA-to-NHP and is able to discriminate between
different patient populations. The diagnostic potential is to be confirmed in
future research.
PMID- 23153837
TI - How politics trumped peer review at Texas cancer institute.
PMID- 23153838
TI - Multiple enlarging nodules on the lower limb.
PMID- 23153839
TI - Dry eye.
PMID- 23153840
TI - Annual health checks for people with intellectual disabilities.
PMID- 23153841
TI - Government disputes that half of NHS efficiency savings came from staff pay
freeze.
PMID- 23153842
TI - Carbamazepine-induced hypersensitivity syndrome in chronic schizophrenia.
AB - Drug-induced hypersensitivity syndrome is a clinically important issue. We report
a case of carbamazepine-induced hypersensitivity syndrome in a 35-year-old
schizophrenia patient. This patient had no previous food or medication allergy
history and presented a negative test result of HLA-B*1502 genotype. After 19
days exposure of carbamazepine, high fever up to 39.4 degrees C, leucopenia
(1670/mm3), proteinuria and bilateral lung field infiltration were developed.
These clinically significant physical conditions resolved after discontinuing
carbamazepine. The importance of genetic susceptibility other than HLA-B*1502
should not be overlooked in drug-induced hypersensitivity syndrome.
PMID- 23153843
TI - The effect of age on outcomes of coronary artery bypass surgery compared with
balloon angioplasty or bare-metal stent implantation among patients with
multivessel coronary disease. A collaborative analysis of individual patient data
from 10 randomized trials.
AB - OBJECTIVES: This study sought to assess whether patient age modifies the
comparative effectiveness of coronary artery bypass graft (CABG) surgery and
percutaneous coronary intervention (PCI). BACKGROUND: Increasingly, CABG and PCI
are performed in older patients to treat multivessel disease, but their
comparative effectiveness is uncertain. METHODS: Individual data from 7,812
patients randomized in 1 of 10 clinical trials of CABG or PCI were pooled. Age
was analyzed as a continuous variable in the primary analysis and was divided
into tertiles for descriptive purposes (<=56.2 years, 56.3 to 65.1 years, >=65.2
years). The outcomes assessed were death, myocardial infarction and repeat
revascularization over complete follow-up, and angina at 1 year. RESULTS: Older
patients were more likely to have hypertension, diabetes, and 3-vessel disease
compared with younger patients (p < 0.001 for trend). Over a median follow-up of
5.9 years, the effect of CABG versus PCI on mortality varied according to age
(interaction p < 0.01), with adjusted CABG-to-PCI hazard ratios and 95%
confidence intervals (CI) of 1.23 (95% CI: 0.95 to 1.59) in the youngest tertile;
0.89 (95% CI: 0.73 to 1.10) in the middle tertile; and 0.79 (95% CI: 0.67 to
0.94) in the oldest tertile. The CABG-to-PCI hazard ratio of less than 1 for
patients 59 years of age and older. A similar interaction of age with treatment
was present for the composite outcome of death or myocardial infarction. In
contrast, patient age did not alter the comparative effectiveness of CABG and PCI
on the outcomes of repeat revascularization or angina. CONCLUSIONS: Patient age
modifies the comparative effectiveness of CABG and PCI on hard cardiac events,
with CABG favored at older ages and PCI favored at younger ages.
PMID- 23153844
TI - In silico cardiac risk assessment in patients with long QT syndrome: type 1:
clinical predictability of cardiac models.
AB - OBJECTIVES: The study was designed to assess the ability of computer-simulated
electrocardiography parameters to predict clinical outcomes and to risk-stratify
patients with long QT syndrome type 1 (LQT1). BACKGROUND: Although attempts have
been made to correlate mutation-specific ion channel dysfunction with patient
phenotype in long QT syndrome, these have been largely unsuccessful. Systems
level computational models can be used to predict consequences of complex changes
in channel function to the overall heart rhythm. METHODS: A total of 633 LQT1
genotyped subjects with 34 mutations from multinational long QT syndrome
registries were studied. Cellular electrophysiology function was determined for
the mutations and introduced in a 1-dimensional transmural electrocardiography
computer model. The mutation effect on transmural repolarization was determined
for each mutation and related to the risk for cardiac events (syncope, aborted
cardiac arrest, and sudden cardiac death) among patients. RESULTS: Multivariate
analysis showed that mutation-specific transmural repolarization prolongation
(TRP) was associated with an increased risk for cardiac events (35% per 10-ms
increment [p < 0.0001]; >=upper quartile hazard ratio: 2.80 [p < 0.0001]) and
life-threatening events (aborted cardiac arrest/sudden cardiac death: 27% per 10
ms increment [p = 0.03]; >=upper quartile hazard ratio: 2.24 [p = 0.002])
independently of patients' individual QT interval corrected for heart rate (QTc).
Subgroup analysis showed that among patients with mild to moderate QTc duration
(<500 ms), the risk associated with TRP was maintained (36% per 10 ms [p <
0.0001]), whereas the patient's individual QTc was not associated with a
significant risk increase after adjustment for TRP. CONCLUSIONS: These findings
suggest that simulated repolarization can be used to predict clinical outcomes
and to improve risk stratification in patients with LQT1, with a more pronounced
effect among patients with a lower-range QTc, in whom a patient's individual QTc
may provide less incremental prognostic information.
PMID- 23153845
TI - In silico to in vivo: mutation-specific modeling of arrhythmia risk.
PMID- 23153846
TI - Aged human cells rejuvenated by cytokine enhancement of biomaterials for surgical
ventricular restoration.
AB - OBJECTIVES: This study investigated whether cytokine enhancement of a
biodegradable patch could restore cardiac function after surgical ventricular
restoration (SVR) even when seeded with cells from old donors. BACKGROUND: SVR
can partially restore heart size and improve function late after an extensive
anterior myocardial infarction. However, 2 limitations include the stiff
synthetic patch used and the limited healing of the infarct scar in aged
patients. METHODS: We covalently immobilized 2 proangiogenic cytokines (vascular
endothelial growth factor and basic fibroblast growth factor) onto porous
collagen scaffolds. We seeded human mesenchymal stromal cells from young (50.0 +/
8.0 years, N = 4) or old (74.5 +/- 7.4 years, N = 4) donors into the scaffolds,
with or without growth factors. The patches were characterized and used for SVR
in a rat model of myocardial infarction. Cardiac function was assessed. RESULTS:
In vitro results showed that cells from old donors grew slower in the scaffolds.
However, the presence of cytokines modulated the aging-related p16 gene and
enhanced cell proliferation, converting the old cell phenotype to a young
phenotype. In vivo studies showed that 28 days after SVR, patches seeded with
cells from old donors did not induce functional recovery as well as patches
seeded with young cells. However, cytokine-enhanced patches seeded with old cells
exhibited preserved patch area, prolonged cell survival, and augmented
angiogenesis, and rats implanted with these patches had better cardiac function.
The patch became an elastic tissue, and the old cells were rejuvenated.
CONCLUSIONS: This sustained-release, cytokine-conjugated system provides a
promising platform for engineering myocardial tissue for aged patients with heart
failure.
PMID- 23153847
TI - Buying new soul.
PMID- 23153848
TI - Combined subaortic and mid-ventricular obstruction with significant aortic
stenosis diagnosed by triphasic Doppler flow pattern: multiple levels of left
ventricular outflow tract obstruction.
PMID- 23153849
TI - Gratitude.
PMID- 23153851
TI - "Super-responders" and "hypo-responders": neglecting the obvious question?
PMID- 23153852
TI - Absence of cardiovascular implantable electronic device infection in remote
implantations demonstrated by fluorine-18 positron emission tomography.
PMID- 23153854
TI - Live myxoma embolism.
PMID- 23153855
TI - Methodological differences between pharmacological treatment guidelines for
bipolar disorder: what to do for the clinicians?
AB - OBJECTIVE: Numerous guidelines for bipolar disorder have been published. The aim
of this article is to underline the main differences between consensus-based
guidelines (CBG) and evidence-based guidelines (EBG) currently available for the
management of bipolar disorder. METHODS: A literature search for guidelines
published since 2006 was performed. A qualitative analysis was then conducted to
compare the methodologies and the guidelines contents. RESULTS: Comparison
between CBG and EBG found more similarities than differences. However,
discordances were found in the first-line choice of treatment (monotherapy or
combination, use of lamotrigine or lithium in bipolar depression), time to
reassessment and duration of maintenance treatment, introduction as from the
acute phase a regimen compatible with long-term use and pharmacotherapy during
pregnancy. CONCLUSIONS: The choice of policy, whatever the methodology used, is
up to the authors and can, therefore, depend on their interpretation of the
available scientific evidence. Combining both methodologies (CBG and EBG) enables
us to meet the complete definition of evidence-based medicine.
PMID- 23153856
TI - Two-round Delphi technique for the consensual design of a paediatric
pharmaceutical care model.
AB - The main goal of clinical pharmacists is to improve patient care quality by
providing individualised care. This is achieved by validating prescriptions and
performing pharmacotherapeutic follow-up, leading to effective, safe and
efficient drug therapy. However, there is no specific model for medication order
validation in paediatrics addressing the distinct issues of paediatric drug use
or the greater susceptibility of medication errors occurring in this patient
group. For this reason we intended to design and reach consensus on a paediatric
pharmaceutical care model by applying a two-round Delphi technique. In order to
define the levels of complexity in reaching consensus for the model, three
variables were taken into account: level of access to patient medical and drug
records (partial vs. total), access to medical and nursing staff attending the
patient (on-site vs. off-site) and the pharmacist available time (limited vs.
adequate). In order to describe the minimum items to be included in the
validation process at each of the three levels of complexity, we analysed the
safety profile in the medication order prescription previously defined in an
epidemiological study in eight hospitals with a total capacity of 1565 paediatric
beds. A panel of experts was recruited (50 experts from 20 different hospitals)
and the questionnaire was completed. Consensus was established at 70% of
agreement by experts for an item. Following debate on the items that did not
obtain consensus, a second round was performed, after which the final consensus
model was defined. After two rounds of consultation, consensus was obtained for
39 out of the 41 items that were surveyed. Of these, 17 were then used for the
basic validation model (e.g. weight/age check, dose/weight check), 13 were
implemented in the intermediate level (e.g. identification of adverse effects
from excipients) and 9 were incorporated at advanced level (e.g. reconciliation
at discharge for patients at risk). By applying the model, based on homogenous
criteria for action, the clinical pharmacist's role will improve, and in turn,
this will doubtlessly reduce drug errors through medication order validation.
PMID- 23153857
TI - Predictors of patient-reported recovery from motor or sensory deficits two years
after acute symptomatic lumbar disk herniation.
AB - OBJECTIVE: To determine the prevalence of patient-reported recovery from motor or
sensory deficits over 2 years of follow-up after acute symptomatic lumbar disk
herniation and to identify predictors of perceived recovery. DESIGN: A
prospective inception cohort. SETTING: An outpatient spine clinic. PATIENTS:
Consecutive adults with lumbosacral radicular syndrome (onset <=12 weeks) due to
symptomatic lumbar disk herniation, confirmed by magnetic resonance imaging: 95
patients with a baseline motor deficit by physical examination and 59 patients
with a baseline sensory deficit by physical examination. METHODS: The patients
received individualized nonsurgical treatment or, in a minority of cases,
surgical treatment. All of the patients underwent a standardized baseline
neurologic examination, including motor and sensory testing. Patients with a
motor or sensory deficit at the baseline examination reported on whether they
perceived persisting weakness or sensory deficits at 1- and 2-year follow-up. We
calculated the 1- and 2-year prevalence of patient-reported persisting weakness
or sensory deficits. We examined factors associated with perceived recovery from
motor or sensory deficits by using bivariate analyses and multivariate logistic
regression. RESULTS: Among patients with a baseline motor deficit, the prevalence
of patient-reported continuing weakness was 38% at 1 year and 25% at 2 years.
Among patients with a baseline sensory deficit, the prevalence of patient
reported continuing sensory deficits was 53% at 1 year and 47% at 2 years. A
positive straight leg raise test (odds ratio [OR] 0.26 [95% confidence interval
(CI) 0.08-0.83]) and opioid use (OR 0.24 [95% CI 0.06-0.83]) were independently
and negatively predictive of patient-reported motor recovery. Female gender was
independently and negatively predictive of patient-reported sensory recovery (OR
0.20 [95% CI 0.04-0.99]). CONCLUSIONS: Patient-reported recovery from motor
deficits after lumbar disk herniation occurs for 75% of patients over 2 years,
but recovery from sensory deficits over this time frame occurs in only 53% of
patients. A positive straight-leg raise test and female gender may predict poor
recovery from motor and sensory deficits, respectively.
PMID- 23153858
TI - What is evaluation of hematuria by primary care physicians? Use of electronic
medical records to assess practice patterns with intermediate follow-up.
AB - BACKGROUND: To determine whether patients found to have hematuria by their
primary care physicians are evaluated according to best practice policy.
MATERIALS AND METHODS: The University of Texas Southwestern Medical Center
maintains institutional outpatient electronic medical records (EMR) that are used
by all providers in all specialties. We conducted an Institutional Review Board
approved observational study of patients found to have more than 5 red blood
cells/high power field between March 2009 and February 2010. RESULTS: There were
449 patients of whom the majority were female (82%), Caucasian (39%), with
microscopic hematuria (MH) (85%). Almost 58% of patients were initially
symptomatic with urinary symptoms or pain. Evaluation for the source of hematuria
was limited and included imaging (35.6%), cystoscopy (9%, and cytology (7.3%).
Only 36% of men and 8% of women were referred to a urologist. No abnormality was
found in 32% and 51% of patients with gross hematuria and MH, respectively (P =
0.004). There were 4 bladder tumors and 1 renal mass detected. Male gender,
ethnicity and gross (vs. microscopic) hematuria were associated with higher rate
of urological referral. Advanced age, smoking, provider practice type, and the
presence of urinary symptoms were not associated with an increase rate of
urological referral. No additional cancers were diagnosed with 29-month follow
up. CONCLUSIONS: While urinalysis remains a common diagnostic tool, most cases of
both microscopic and gross hematuria are not fully evaluated according to
guidelines. Use of cystoscopy, cytology, and upper tract imaging is limited.
Further studies will be needed to determine the extent of the problem and impact
on morbidity and survival.
PMID- 23153859
TI - Serum levels of chromogranin A are not predictive of high-grade, poorly
differentiated prostate cancer: results from an Italian biopsy cohort.
AB - OBJECTIVES: To explore the association of chromogranin A (CgA) levels and the
risk of poorly differentiated prostate cancer (CaP) in men undergoing prostate
biopsy. MATERIALS AND METHODS: Between 2006 and 2012, we prospectively enrolled
1,018 men with no history of CaP undergoing prostate biopsy. The risk of
detecting poorly differentiated CaP as a function of CgA concentration was
evaluated using crude and adjusted logistic regressions. Further analyses were
performed to determine whether CgA was a significant predictor of high-grade CaP
in men with low PSA (<10 ng/ml). RESULTS: We found a significantly higher level
of CgA in men with poorly differentiated CaP. CgA was however co-linear with age,
and serum CgA levels were not significantly associated with the overall risk of
CaP, and the specific risk of poorly differentiated CaP (OR 1.001 95% CI 0.99
1.01, P = 0.74). Moreover, in men with low PSA levels (<10 ng/ml), CgA was not a
significant predictor of high grade-disease on univariate (OR 1.00; 95% CI 0.99
1.01; P = 0.66) and multivariate analysis (P = 0.85). CONCLUSIONS: In our cohort
of patients, the serum level of CgA is not a significant predictor of poorly
differentiated CaP on initial prostate biopsy, even in men with low PSA levels
(<10 ng/ml). According to our experience, CgA should not be considered a reliable
marker to predict poorly differentiate cancer in the setting of initial prostate
biopsy.
PMID- 23153860
TI - An investigation into the adsorption of thorium(IV) from aqueous solutions by a
carboxylate-functionalised graft copolymer derived from titanium dioxide
densified cellulose.
AB - The use of a carboxylate-functionalized graft copolymer (PGTDC-COOH) based on
titanium dioxide-densified cellulose (TDC) for the removal and recovery of
thorium(IV) [Th(IV)] from industrial wastewater is reported in this paper.
Infrared spectroscopy and X-ray diffractometer were used to characterize the
adsorbent material. Batch equilibrium experiments showed that the adsorbent
exhibited 98.6 +/- 3.1% adsorption from an initial concentration of 10 mg/L
Th(IV) solution at pH 5.0. The sorption kinetics have been analysed by pseudo
first-order and pseudo-second-order kinetic models and the adsorption kinetics
was described by pseudo-second-order model. The experimental data obeyed Langmuir
isotherm and the maximum monolayer adsorption capacity for Th(IV) was also found
to be 92.23 +/- 2.4 mg/g at 30 degrees C. The desorption capacity of HCl
concentrations of different strengths ranging from 0.001 to 0.1 M was also
studied. Maximum desorption of 98.2 +/- 2.8% for Th(IV) occurred with 0.1 M HCl.
The adsorption efficiency towards Th(IV) ion removal was tested using artificial
sea water. Almost complete removal was possible with 3.5 g of the adsorbent from
1 L of the sea water.
PMID- 23153861
TI - Natural radioactivity determination in samples of Peperomia pellucida commonly
used as a medicinal herb.
AB - The concentration of (238)U, (232)Th, (230)Th, (226)Ra, (228)Ra and (210)Pb were
determined in samples of Peperomia pellucida and in the surrounding soil, by
alpha spectrometry and gross alpha and beta counting. The radionuclide activity
concentrations ranged from 4.3 to 38 Bq kg(-1), 1.7-124 Bq kg(-1), 2.1-38 Bq kg(
1), 8.5-37 Bq kg(-1), 3.2-46 Bq kg(-1), 39-93 Bq kg(-1), respectively. In the
plant extractions and infusions as used for consumption, the mean recoveries were
from 23% to 60% in maceration and 24-75% in infusion.
PMID- 23153862
TI - Impact of a dedicated cancer center surveillance program on guideline adherence
for patients with stage II and III colorectal cancer.
AB - Surveillance after curative treatment for stage II/III colorectal cancer
identifies surgically resectable disease and improves survival. We evaluated
adherence to guidelines and outcomes for 408 patients enrolled in an innovative
follow-up program at our cancer center. We found that a dedicated intensive
surveillance program can impact adherence to guidelines for patients with
colorectal cancer. BACKGROUND: Our aims were to evaluate adherence to guidelines
on colorectal cancer surveillance and outcomes for patients enrolled in an
innovative follow-up program at our cancer center. PATIENTS AND METHODS: A
retrospective chart review was conducted at the Cross Cancer Institute in
Edmonton, Canada. Patients with stage II/III colorectal cancer who completed
treatment and who entered into the program from December 1, 2007, to December 31,
2009, were identified. The minimum standard of care follow-up was defined as (1)
carcinoembryonic antigen (CEA) testing every 120 days for 3 years; (2) computed
tomography of chest, abdomen, and pelvis at 10 to 14 months and 22 to 26 months
after surgery; and (3) colonoscopy within 14 months of surgery. RESULTS: A total
of 408 patients met inclusion criteria. Two hundred (49.0%) patients were
adherent to all 3 components of surveillance. Among all patients, 57 (14.0%) were
nonadherent to computed tomography imaging, 135 (33.1%) were nonadherent to
colonoscopy, and 96 (23.5%) were nonadherent to CEA testing. Determinants of
nonadherence are described. In total, 192 (47.2%) patients had an abnormal
surveillance investigation that led to 307 follow-up events. After a median of
1.6 years, 69 (16.9%) patients had documented tumor recurrence. Sixty-one (88.4%)
of these 69 patients had recurrence diagnosed via surveillance, and 31 (44.9%)
patients were considered potentially resectable. CONCLUSIONS: Our study
demonstrated an improvement in CEA testing since the program began; however,
adherence rates for all components are not yet optimal. Alterations to
surveillance program management are outlined. Further investigation will
determine whether intense follow-up improves patient survival locally.
PMID- 23153863
TI - Pediatric ischemic stroke: acute management and areas of research.
PMID- 23153864
TI - Patterns of catch-up growth.
PMID- 23153865
TI - Response to letter to the editor: "support for burn splint research".
PMID- 23153866
TI - Autograft fat in neurological surgery.
PMID- 23153867
TI - Utility of magnetization transfer T1 imaging in children with seizures.
AB - Failure to detect FCD and similar lesions encountered in patients with tuberous
sclerosis can have significant clinical consequences, such as preventing surgical
intervention for medically refractory epilepsy and misguiding prognostic
information regarding cognitive development. Here, we show the beneficial effects
on detection of FCD and cortical tubers when using a magnetization transfer T1
sequence for children with seizures who underwent MR imaging at our institution.
PMID- 23153868
TI - Effect of patient sex on white matter alterations in unilateral medial temporal
lobe epilepsy with hippocampal sclerosis assessed by diffusion tensor imaging.
AB - BACKGROUND AND PURPOSE: Studies shows ictal behavior and symptoms are affected by
patient sex in temporal lobe epilepsy. The purpose of our study was to determine
whether alterations in the WM as assessed by DTI display different patterns in
male and female patients with unilateral HS. MATERIALS AND METHODS: Patients with
unilateral HS were categorized as women with right HS (n=12), men with right HS
(n=10), women with left HS (n=12), and men with left HS (n=10). DTI of the brain
along 64 noncollinear directions was obtained from 44 patients and 37 sex-matched
control participants. We used TBSS to analyze whole-brain WM. Regions with
significant changes of FA and MD, and their mean FA, MD, total number of
significant voxels, and asymmetry indices were determined for each group.
RESULTS: All groups showed bilateral and extensive reductions of FA and elevated
MD in the WM, more prominent ipsilateral to the affected hippocampus. The total
number of voxels with decreased FA in patients compared with that of control
participants was higher in women with right HS (24,727 vs 5,459) and in men with
left HS (27,332 vs 14,013) than in their counterparts. Changes in MD associated
with right HS were more extensive in both men and women (right vs left HS, women:
16,926 vs 5,458; men: 5,389 vs 4,764) than in those with left HS. In patients
with right HS, the ipsilateral cingulum, uncinate fasciculus, internal and
external capsules, and right acoustic radiation were involved extensively in
women. CONCLUSIONS: Women and men showed different patterns in extent of WM
alterations associated with HS.
PMID- 23153870
TI - Thrombosis heralding aneurysmal rupture: an exploration of potential mechanisms
in a novel giant swine aneurysm model.
AB - BACKGROUND AND PURPOSE: The relationship between aneurysm dimensions, flow,
thrombosis, and rupture remains poorly understood. We attempted to clarify this
relationship by exploring various swine aneurysm models. MATERIALS AND METHODS:
Bilateral carotid aneurysms were constructed according to 3 protocols in 24
animals: small aneurysms with wide necks (group 1; n = 6 animals); small
aneurysms with small necks (group 2; n = 4 animals), and giant aneurysms with
large necks (group 3; n = 14 animals). Group 3 included 3 subgroups, related to
testing the model in various experimental conditions: The neck was clipped in 3
animals; venous pouches lacked an endothelial lining in 4 animals; and 7 were
control animals. Animals were followed until rupture, or for 1-4 weeks.
Angiography was performed postoperatively and before euthanasia. We studied
lesion pathology, paying attention to thrombosis, recanalization, wall
composition, and perianeurysmal hemorrhage. RESULTS: Groups differed
significantly in aneurysm dimensions and aspect ratio (P = .002). Ruptures
occurred more frequently in animals with untreated giant aneurysms (7/7) than in
animals with small wide-neck (0/6) or small-neck (2/4) aneurysms (P = .002).
Ruptures occurred only in animals with thrombosed aneurysms. Lesions lacking an
endothelial lining and 5 of 6 clipped venous pouches thrombosed but did not
rupture. One giant lesion ruptured despite complete clipping. The wall was
deficient in alpha-actin and was infiltrated with inflammatory cells and
erythrocytes in all thrombosed cases, ruptured or not. Ruptures were associated
with recanalizing channels in 9 of 10 cases. CONCLUSIONS: Thrombosis,
inflammation, and recanalization may precipitate aneurysmal ruptures in a swine
model.
PMID- 23153869
TI - Insula and orbitofrontal cortical morphology in substance dependence is modulated
by sex.
AB - BACKGROUND AND PURPOSE: Frontolimbic circuits are involved in learning and
decision-making processes thought to be affected in substance-dependent
individuals. We investigated frontolimbic cortical morphometry in substance
dependent men and women and determined whether morphometric measurements
correlated with decision-making performance. MATERIALS AND METHODS: Twenty-eight
abstinent SDI (17 men/11 women) were compared with 28 controls (13 men/15 women).
Cortical thicknesses and volumes were computed by using FreeSurfer. After
controlling for age and intracranial volume, group and sex effects were analyzed
in 3 a priori regions of interest: the insula, orbitofrontal cortex, and anterior
cingulate cortex by using analysis of covariance. A secondary whole-brain
analysis was conducted to verify region-of-interest results and to explore
potential differences in other brain regions. RESULTS: Region-of-interest
analyses revealed a main effect of group on the left insula cortex, which was
thinner in SDI compared with controls (P = .02). There was a group by sex
interaction on bilateral insula volume (left, P = .02; right, P = .001) and right
insula cortical thickness (P = .007). Compared with same-sex controls, female SDI
had smaller insulae, whereas male SDI had larger insulae. Neither ACC nor OFC
significantly differed across group. Performance on a decision-making task was
better in controls than SDI and correlated with OFC measurements in the controls.
CONCLUSIONS: SDI and controls differed in insula morphology, and those
differences were modulated by sex. No group differences in OFC were observed, but
OFC measurements correlated with negative-reinforcement learning in controls.
These preliminary results are consistent with a hypothesis that frontolimbic
pathways may be involved in behaviors related to substance dependence.
PMID- 23153871
TI - CT fluoroscopy-guided cervical interlaminar steroid injections: is it overkill?
PMID- 23153872
TI - How to value technological innovation: a proposal for determining relative
clinical value.
PMID- 23153873
TI - Two patients with a solitary fibrous tumor of the thoracic spinal cord.
AB - We report two patients with thoracic spinal solitary fibrous tumor (SFT). This
report includes a patient with the first secondary SFT arising in the central
nervous system from a pleural origin to our knowledge. The diagnosis was
confirmed by histological and immunohistochemical analysis. Both patients
underwent gross total resection of their tumors and did not show signs of local
recurrence. The patient with the secondary lesion later presented with visceral
dissemination. We review the reports of spinal SFT and discuss the diagnosis and
therapeutic management of this intriguing entity.
PMID- 23153874
TI - Patient safety in the critical care environment.
AB - Improving the quality and safety of intensive care unit (ICU) care in the United
States is a significant challenge for the future. Obtaining improvement in
systems of care is difficult given the reactionary mode physicians tend to enter
when dealing with moment-to-moment crises. It will be important to implement
quality and safety measures that are already supported by evidence. Improvement
of device safety will be critical to reducing the large number of device-related
complications that occur in US ICUs. Prospective collection of adverse events
with rigorous analysis will be important to allow systematic errors to be exposed
and corrected.
PMID- 23153875
TI - Monitoring devices in the intensive care unit.
AB - Monitors in the intensive care unit are imperative to taking adequate care of
these critically ill patients. Cardiovascular, pulmonary, and neurologic monitors
are key to performing these tasks. This article gives an overview of the most
common monitors that are used in the intensive care unit.
PMID- 23153876
TI - Hypovolemic shock resuscitation.
AB - Several changes in the way patients with hemorrhagic shock are resuscitated have
occurred over the past decades, including permissive hypotension, minimal
crystalloid resuscitation, earlier blood transfusion, and higher plasma and
platelet-to-red cell ratios. Hemostatic adjuncts, such as tranexamic acid and
prothrombin complex, and the use of new methods of assessing coagulopathy are
also being incorporated into resuscitation of the bleeding patient. These ideas
have been incorporated by many trauma centers into institutional massive
transfusion protocols, and adoption of these protocols has resulted in
improvements in mortality and morbidity. This article discusses each of these new
resuscitation strategies and the evidence supporting their use.
PMID- 23153877
TI - Epidemiology of sepsis in surgical patients.
AB - Sepsis in the surgical patient continues to be a common and potentially lethal
problem. Early identification of patients and timely implementation of evidence
based therapies continue to represent significant clinical challenges for care
providers. The implementation of a sepsis screening program in conjunction with
protocol for the delivery of evidence-based care and rapid source control can
improve patient outcomes. The article provides definitions and guidelines for the
screening and management of sepsis and septic shock.
PMID- 23153878
TI - The value of critical care.
AB - The primary focus of this review is on the cost-effectiveness of critical care.
The rapid growth in health care expenditures has engendered careful scrutiny of
the practice of medicine with regard not only to effectiveness but also to
efficiency. This shift necessitates that physicians understand the effectiveness
of their interventions and the cost at which this effectiveness is obtained. Cost
effectiveness and cost-utility analyses have become crucial evaluative tools in
medicine. Explicit articulation of comparative cost-effectiveness facilitates the
allocation of limited resources. Physicians and policy-makers must evaluate such
studies with caution, skepticism, and attention to the methods used.
PMID- 23153879
TI - Mechanical ventilation.
AB - The treatment of respiratory failure requiring mechanical ventilation has
advanced significantly over the last 20 years. The goal of therapy in patients
with acute respiratory distress syndrome should be to optimize oxygenation while
minimizing the risk of ventilator-induced lung injury and providing adequate
ventilation. Appropriate use of ventilation modes and strategies, positive-end
expiratory pressure levels, and recruitment maneuvers can improve oxygen
delivery. Salvage therapies, such as prone positioning, inhaled epoprostenol and
nitric oxide, and high-frequency oscillatory ventilation, have a well-established
role in supportive management and are associated with improved oxygenation but
not survival.
PMID- 23153880
TI - Removing the critically ill patient from mechanical ventilation.
AB - Weaning from mechanical ventilation is usually straightforward but is
occasionally challenging. Sedation must be used at the appropriate times and with
appropriate dosing. A protocol that calls for a daily sedation holiday with a
spontaneous breathing trial decreases time on the ventilator. Early tracheostomy
is beneficial in traumatic brain injury patients. Noninvasive ventilation is most
useful in patients with baseline obstructive sleep apnea and chronic obstructive
pulmonary disease.
PMID- 23153881
TI - Enteral nutrition in the critically ill patient.
AB - Timing and route of nutrition provided to critically ill patients can affect
their outcome. Early enteral nutrition has been shown to decrease specifically
infectious morbidity in the critically ill patient. There is a small group of
patients who are malnourished on arrival to the intensive care unit and in these
patients parenteral nutrition is beneficial.
PMID- 23153882
TI - Renal management in the critically ill patient.
AB - Acute kidney injury is common in the hospital setting and morbidity and mortality
outcomes depend on early recognition and early intervention. Identifying patients
at risk of acute kidney injury is critical in prevention, early identification,
and appropriate treatment.
PMID- 23153883
TI - Common complications in the critically ill patient.
AB - Critically ill patients in intensive care units are subject to many complications
associated with therapy. Many of these complications are health care-associated
infections and are related to indwelling devices, including ventilator-associated
pneumonia, central line-associated bloodstream infection, catheter-associated
urinary tract infection; surgical site infection, venous thromboembolism, deep
venous thrombosis, and pulmonary embolus are other common complications. All
efforts should be undertaken to prevent these complications in surgical critical
care, and national efforts are under way for each of these complications. In this
article, epidemiology, risk factors, diagnosis, treatment, and prevention of
these complications in critically ill patients are discussed.
PMID- 23153884
TI - Heparin-induced thrombocytopenia.
AB - This article deals with heparin-induced thrombocytopenia. It discusses the
pathophysiology of the disease, as well as the diagnostic challenges and
therapeutic management. The incidence of the disease and screening
recommendations are reviewed. The article also emphasizes the importance of
correct diagnosis and treatment options. This article is intended for surgeons in
all specialties and levels of training.
PMID- 23153885
TI - Optimizing drug therapy in the surgical intensive care unit.
AB - This article provides a review of commonly prescribed medications in the surgical
ICU, focusing on sedatives, antipsychotics, neuromuscular blocking agents,
cardiovascular agents, anticoagulants, and antibiotics. A brief overview of
pharmacology is followed by practical considerations to aid prescribers in
selecting the best therapy within a given category of drugs to optimize patient
outcomes.
PMID- 23153886
TI - Pain management in the ICU.
AB - Pain management in the intensive care unit (ICU) is a complex process. Both the
experience of pain as well as its treatment can have consequences relating to the
overall outcome of the patient. Further, lack of the ability of many patients in
the ICU to communicate their distress makes it even more critical for the ICU
practitioner to understand the typical causes of pain in this setting and the
applicability of many pain management regimens.
PMID- 23153887
TI - Family engagement regarding the critically ill patient.
AB - The Institute of Medicine strongly recommends a health care system that supports
family members. Nowhere is the need for family-centered care greater than with
critically ill patients. Simplistically, family-centered care is primarily about
communication. Unfortunately, family perception of communication in the intensive
care unit (ICU) is quite poor. This article reviews some strategies to improve
communication, including family meetings and family presence at resuscitation. It
also highlights some of the areas within the realm of ICU care in which family
engagement is particularly important, including advance directives, end-of-life
care, brain death, and organ donation.
PMID- 23153889
TI - A case study in intra-abdominal sepsis.
AB - Intra-abdominal infections are a common problem for the general surgeon and major
sources of morbidity and mortality in the intensive care unit. Some of these
patients present with peritonitis that can rapidly progress to septic shock. The
basic principles of care include prompt resuscitation, antibiotics, and source
control. This article will use a detailed case study to outline the management of
a patient with severe intra-abdominal infection from diverticulitis from initial
resuscitation to reconstruction. Components of the Surviving Sepsis Campaign as
they pertain to surgical patients are discussed and updated, and the concept of
damage control general surgery is applied.
PMID- 23153888
TI - A case study of a multiply injured patient.
AB - Initial evaluation of severely injured patients requires an organized, rapid, and
thorough evaluation of the patient where life-threatening injuries are identified
and treated simultaneously. A case study provides the basis for discussion of the
management of the multiply injured trauma patient. The ultimate goal in
rehabilitation of a multiply injured patient is to return each patient to as much
independent function and ability to contribute to society as possible.
PMID- 23153890
TI - Two case studies of cardiopulmonary effects of intra-abdominal hypertension.
AB - Intra-abdominal hypertension falsely elevates the pulmonary artery pressure.
Volumetric pulmonary artery catheter monitoring is an optionfor estimating
preload in this condition. Treatment of intra-abdominal hypertension begins with
medical therapy but once abdominal compartment syndrome develops it requires
decompressive laparotomy for definitive management. Pulmonary hypertension
reduces cardiac function which may be improved with inotropes that simultaneously
reduce pulmonary artery pressure. Oxygenation may be improved with elevated PEEP
and FiO(2).
PMID- 23153891
TI - Surgical critical care.
PMID- 23153892
TI - Surgical critical care.
PMID- 23153893
TI - Social dysfunction in first-episode psychosis and relations to neurocognition,
duration of untreated psychosis and clinical symptoms.
AB - Signs of social dysfunction are present early in the course of psychotic
disorders. There is a lack of knowledge about how premorbid function, illness
history, psychotic symptoms and neurocognitive characteristics are related to
social function in patients with first episode psychosis (FEP). The relationship
between these factors could provide important information about the
psychopathology underlying social dysfunction and have implications for future
prevention and treatment efforts. Our objective is to identify early predictors
of social functioning in patients with FEP. We examined 166 patients and 166 age-
and gender-matched healthy controls (HC). We used a validated and comprehensive
measure of social functioning (the Social Functioning Scale), a comprehensive
neurocognitive test battery, in addition to measures of psychotic symptoms,
duration of untreated psychosis (DUP) and premorbid adjustment (the Premorbid
Adjustment Scale). Lower childhood level of social adjustment and lower
psychomotor speed had the strongest influence across measures of social
functioning while symptoms and DUP had a weaker influence. The main result of the
current study is that premorbid social adjustment and psychomotor speed had the
strongest association with measures of social functioning in patients with FEP.
PMID- 23153894
TI - Relevance of serum copper elevation induced by oral contraceptives: a meta
analysis.
AB - BACKGROUND AND STUDY DESIGN: It is well documented that copper (Cu) blood levels
are elevated in combination oral contraceptive (COC) users. The aim of this study
was to establish the range of Cu increase in OC users compared to nonusers
through a systematic literature overview and quantitative data analysis. RESULTS:
Twenty-six articles were included in the meta-analysis. The increase in Cu level
exponentially decreased in COC users over time, with a rapid decline through the
1960s and 1970s. After controlling for the publication year, use of COC increases
the mean serum/plasma Cu level by 0.57 mg/L (95% confidence interval 0.49-0.66
mg/L). CONCLUSION: COCs commonly raise serum Cu to levels between 1.5 and 2 mg/L,
which are above reference levels. Although these levels are not considered toxic,
there are suggestions that such Cu increase could be implicated in oxidative
pathophysiological processes in the body. Further research on safety of COCs use,
including oxidative-stress-related effects, is warranted.
PMID- 23153895
TI - Revitalizing long-acting reversible contraceptives in settings with high unmet
need: a multicountry experience matching demand creation and service delivery.
AB - BACKGROUND: Contraception in many developing countries is characterized by high
unmet need, irregular access, low utilization and presumed demand for long-acting
reversible contraceptives (LARCs). STUDY DESIGN: A 13-country initiative focused
on increasing consumer demand and high quality services for intrauterine devices
(IUDs) began in 2009. Services were provided through (a) private sector
franchised or affiliated clinics; (b) providers seconded to the public sector and
(c) special "event" days. Client intake data are used to compare the profile of
IUD acceptors with IUD users from representative national datasets of select
countries, as well as examine trends in IUD uptake. RESULTS: During 2009-2010,
575,601 IUDs were inserted across the 13 countries. Compared to national IUD
users, users in this project were slightly younger and less educated. Among IUD
acceptors, 24% used no modern method at the time of IUD initiation, and 28%
reported injectable use in the three previous months. CONCLUSIONS: Convenient,
quality, affordable services with demand creation can result in significant
uptake of LARCs in settings with low use.
PMID- 23153896
TI - Fertility goal-based counseling increases contraceptive implant and IUD use in
HIV-discordant couples in Rwanda and Zambia.
AB - BACKGROUND: HIV-discordant heterosexual couples are faced with the dual challenge
of preventing sexual HIV transmission and unplanned pregnancies with the
attendant risk of perinatal HIV transmission. Our aim was to examine uptake of
two long-acting reversible contraceptive (LARC) methods--intrauterine devices
(IUD) and hormonal implants--among HIV-discordant couples in Rwanda and Zambia.
STUDY DESIGN: Women were interviewed alone or with their partner during routine
cohort study follow-up visits to ascertain fertility goals; those not pregnant,
not infertile, not already using LARC, and wishing to limit or delay fertility
for >=3 years were counseled on LARC methods and offered an IUD or implant on
site. RESULTS: Among 409 fertile HIV-discordant Rwandan women interviewed (126
alone, 283 with partners), 365 (89%) were counseled about LARC methods, and 130
(36%) adopted a method (100 implant, 30 IUD). Of 787 fertile Zambian women
interviewed (457 alone, 330 with partners), 528 (67%) received LARC counseling,
of whom 177 (34%) adopted a method (139 implant, 38 IUD). In both countries, a
woman's younger age was predictive of LARC uptake. LARC users reported fewer
episodes of unprotected sex than couples using only condoms. CONCLUSIONS:
Integrated fertility goal-based family planning counseling and access to LARC
methods with reinforcement of dual-method use prompted uptake of IUDs and
implants and reduced unprotected sex among HIV-discordant couples in two African
capital cities.
PMID- 23153897
TI - The effect of immediate postpartum depot medroxyprogesterone on early
breastfeeding cessation.
AB - BACKGROUND: This study evaluated the effect of immediate postpartum depot
medroxyprogesterone (DMPA) on breastfeeding cessation within 6 weeks postpartum.
STUDY DESIGN: At low-income-serving obstetric and pediatric clinics, eligible
mothers within 1 year postpartum were recruited to participate in a retrospective
cohort study. The 183 participants completed a self-administered survey. Surveys
were merged with birth certificate data and perinatal maternal/infant medical
records. Kaplan-Meier distributions assessed the relationship between DMPA use
and breastfeeding cessation. A multivariable Cox proportional hazards model
estimated hazard ratios (HRs) and included five known risk factors (age,
education, race, parity and parental cohabitation) and identified potential
confounders. RESULTS: Consistent with the biologic model, the Kaplan-Meier
results raised the possibility of a detrimental effect of DMPA on duration of any
breastfeeding, but differences in these distributions did not achieve statistical
significance (p=.24); after adjustment for potential confounders, this
nonstatistically significant association remained (HR: 1.22; confidence interval:
0.75-1.98). CONCLUSION: Given the state of the evidence, it is unclear whether a
causal effect does or does not exist. However, if there is a causal effect of
DMPA on breastfeeding duration, it is minimal. Additional well-designed research
is warranted.
PMID- 23153898
TI - Prolonged monitoring of ethinyl estradiol and levonorgestrel levels confirms an
altered pharmacokinetic profile in obese oral contraceptives users.
AB - BACKGROUND: Pharmacokinetic (PK) parameters based on short sampling times (48 h
or less) may contain inaccuracies due to their dependency on extrapolated values.
This study was designed to measure PK parameters with greater accuracy in obese
users of a low-dose oral contraceptive (OC) and to correlate drug levels with
assessments of end-organ activity. STUDY DESIGN: Obese [body mass index (BMI)
>=30 kg/m2], ovulatory, otherwise healthy women (n=32) received an OC containing
20 mcg ethinyl estradiol (EE)/100 mcg levonorgestrel (LNG) for two cycles. EE and
LNG PK parameters were characterized for 168 h at the end of Cycle 1. During
cycle 2, biweekly outpatient visits were performed to assess cervical mucus,
monitor ovarian activity with transvaginal ultrasound and obtain serum samples to
measure EE, LNG, estradiol and progesterone levels. PK parameters were calculated
and correlated with end-organ activity and compared against control samples
obtained from normal and obese women sampled up to 48 h in a previous study.
Standard determination of PK accuracy was performed, defined by the dependency on
extrapolated values ('excess' area under the curve of 25% or less). RESULTS: The
mean BMI was 39.4 kg/m2 (SD 6.6) with a range of 30-64 kg/m2. Key LNG PK
parameters were as follows: clearance, 0.52 L/h (SD 0.24); half-life, 65 h (SD
40); area under the curve (AUC), 232 h*ng/mL (SD 102); and time to reach steady
state, 13.6 days (SD 8.4). The majority of subjects had increased ovarian
activity with diameter of follicles >=8 mm (n=25), but only seven women had
follicles >=10 mm plus cervical mucus scores >=5. Evidence of poor end-organ
suppression did not correlate with the severity of the alterations in PK. As
compared to historical normal and obese controls (48-h PK sampling), clearance,
half-life, AUC and time to reach steady state were found to be significantly
different (p<=.05) in obese women undergoing a longer duration of PK sampling
(168 h). Longer sampling also improved PK accuracy for obese women (excess AUC
20%) as compared to both normal and obese controls undergoing shorter sampling
times (48 h) with excess AUCs of 25% and 50%, respectively. CONCLUSIONS: Obesity
results in significant alterations in OC steroid PK parameters, but the severity
of these alterations did not correlate with end-organ suppression. A longer PK
sampling interval (168 h vs. 48 h) improved the accuracy of PK testing.
PMID- 23153899
TI - Calculating contraceptive decisions while intoxicated.
AB - BACKGROUND: Experimental research in laboratory conditions indicates that
intoxication makes unprotected sex more favorable to subjects, while event-level
research indicates little causal effect of intoxication on condom use. Little
work has addressed the effect of intoxication on hormonal contraceptive use.
STUDY DESIGN: This study analyzes in-depth interviews with 30 men and 30 women
between the ages of 18 and 30 years on the East Coast of the United States about
their contraceptive decisions and use. RESULTS: Respondents believed that
frequent intoxication discouraged condom use and consistent contraceptive pill
taking. Their accounts suggested that intoxication discouraged calculated
contraceptive decision-making, and consequently, they mostly reverted to their
standard contraceptive habits. People who were consistent contraceptors sober
were usually consistent contraceptors while intoxicated, and people who were
inconsistent contraceptors sober were usually inconsistent contraceptors while
intoxicated. This pattern applied to both condom use and hormonal contraceptive
use.
PMID- 23153901
TI - The Quick Start Contraception Initiation Method during the 6-week postpartum
visit: an efficacious way to improve contraception in Federally Qualified Health
Centers.
AB - BACKGROUND: About half of all pregnancies in the United States are unplanned, and
many start soon after a previous delivery. Our aim was to determine if the
implementation of the Quick Start Contraception Initiation Method during the 6
week postpartum evaluation could improve the delivery of contraception. STUDY
DESIGN: The medical records of 979 patients seen for their 6-week postpartum
visit at our urban Federally Qualified Health Center (FQHC) between July 2004 and
June 2006 were reviewed. The patients were distributed into two groups defined by
evaluations performed prior to or after the implementation of the new
contraception initiation method. Summary statistics and differences in the
proportions were calculated. A probability of <.05 was considered significant.
RESULTS: The Quick Start Contraception Initiation Method was implemented in July
2005. Five-hundred and sixteen patients were in Group 1, and 463 patients were in
Group 2. Demographic variables were similar among groups. Contraception delivery
rate was 50% in Group 1 and 72% in Group 2 (p<.05). Eighty percent of patients in
Group 1 and 76% of those in Group 2 requested contraception, and 26% of Group 1
and 3% of Group 2 did not receive it. The improvement in dispensing contraception
was most noticeable among teenagers. CONCLUSION: These findings suggest that the
Quick Start Contraception Initiation Method at the time of the 6-week postpartum
evaluation improves the delivery of contraception in FQHCs.
PMID- 23153900
TI - Randomized comparison of two Internet-supported fertility-awareness-based methods
of family planning.
AB - BACKGROUND: The aim was to compare the efficacy and acceptability of two Internet
supported fertility-awareness-based methods of family planning. STUDY DESIGN: Six
hundred and sixty-seven women and their male partners were randomized into either
an electronic hormonal fertility monitor (EHFM) group or a cervical mucus
monitoring (CMM) group. Both groups utilized a Web site with instructions, charts
and support. Acceptability was assessed online at 1, 3 and 6 months. Pregnancy
rates were determined by survival analysis. RESULTS: The EHFM participants
(N=197) had a total pregnancy rate of 7 per 100 users over 12 months of use
compared with 18.5 for the CMM group (N=164). The log rank survival test showed a
significant difference (p<.01) in survival functions. Mean acceptability for both
groups increased significantly over time (p<.0001). Continuation rates at 12
months were 40.6% for the monitor group and 36.6% for the mucus group.
CONCLUSION: In comparison with the CMM, the EHFM method of family planning was
more effective. All users had an increase in acceptability over time. Results are
tempered by the high dropout rate.
PMID- 23153902
TI - Controversies in family planning: desired pregnancy, IUD in situ and no strings
visible.
PMID- 23153903
TI - When can a woman start combined hormonal contraceptives (CHCs)? A systematic
review.
AB - BACKGROUND: Conventional methods of initiating combined hormonal contraceptives
(CHCs), specifically combined oral contraceptives (COCs), the contraceptive patch
and the contraceptive ring, require that women delay starting CHCs until menses
begin, during which time a woman may be at risk of unintended pregnancy. The
objective of this systematic review is to examine the evidence on the risk of
becoming pregnant after starting the method (contraceptive effectiveness
including surrogate measures such as ovarian follicular development and hormone
levels), risk of already being pregnant, side effects and continuation when
starting CHCs on different days of the menstrual cycle. STUDY DESIGN: We searched
the MEDLINE database for all articles (in all languages) published in peer
reviewed journals from inception through March 2012 for evidence relevant to
starting CHCs on different days of the menstrual cycle and the outcomes of
contraceptive effectiveness (including ovarian follicular development and
hormonal levels), side effects and continuation rates. RESULTS: From 1635
reviewed articles, 18 studies met our inclusion criteria. Evidence from four
studies suggests that neither the risk of inadvertently starting COCs in a woman
who is pregnant nor the risk of pregnancy after COC initiation are affected by
the cycle day on which COCs are started. While follicular activity increased as
the cycle day on which COCs were initiated increased, no women ovulated when
starting on Day 5. When starting on Day 7, there was no increase in ovulation for
a 30-mcg pill but a significant increase in ovulation with a 20-mcg pill compared
with starting on Day 1. Evidence from two small studies suggests that 7 days of
pills leads to inhibition of ovulation. One small study suggests that only 3 days
of ring use is needed to inhibit ovulation, but this was following one complete
treatment cycle of ring use. Evidence also suggests that starting CHCs on any day
of the cycle does not affect bleeding problems or other side effects for both
COCs and the patch. While starting CHCs via Quick Start (starting on the day of
the health care visit) may initially increase continuation compared with more
conventional starting strategies, evidence suggests that this difference
disappears over time. CONCLUSION: The body of evidence suggested that (a)
pregnancy rates did not differ by the timing of CHC initiation; (b) the more
follicular activity that occurred prior to starting COCs, the more likely
ovulation was to occur; however, no ovulations were seen when COCs were started
at a follicle diameter of 10 mm (mean cycle day=7.6) or when the ring was started
at follicle diameter of 13 mm (median cycle day=11); (c) bleeding patterns and
other side effects did not vary with the timing of CHC initiation and (d)
continuation rates of CHCs were initially improved by Quick Start, but
differences between groups disappeared over time.
PMID- 23153904
TI - Metabolomic analysis of pancreatic beta cells following exposure to high glucose.
AB - BACKGROUND: Chronic exposure to hyperglycaemic conditions has been shown to have
detrimental effects on beta cell function. The resulting glucotoxicity is a
contributing factor to the development of type 2 diabetes. The objective of this
study was to combine a metabolomics approach with functional assays to gain
insight into the mechanism by which glucotoxicity exerts its effects. METHODS:
The BRIN-BD11 and INS-1E beta cell lines were cultured in 25 mM glucose for 20 h
to mimic glucotoxic effects. PDK-2 protein expression, intracellular glutathione
levels and the change in mitochondrial membrane potential and intracellular
calcium following glucose stimulation were determined. Metabolomic analysis of
beta cell metabolite extracts was performed using GC-MS, 1H NMR and 13C NMR.
RESULTS: Conditions to mimic glucotoxicity were established and resulted in no
loss of cellular viability in either cell line while causing a decrease in
insulin secretion. Metabolomic analysis of beta cells following exposure to high
glucose revealed a change in amino acids, an increase in glucose and a decrease
in phospho-choline, n-3 and n-6 PUFAs during glucose stimulated insulin secretion
relative to cells cultured under control conditions. However, no changes in
calcium handling or mitochondrial membrane potential were evident. CONCLUSIONS:
Results indicate that a decrease in TCA cycle metabolism in combination with an
alteration in fatty acid composition and phosphocholine levels may play a role in
glucotoxicity induced impairment of glucose stimulated insulin secretion. GENERAL
SIGNIFICANCE: Alterations in certain metabolic pathways play a role in
glucotoxicity in the pancreatic beta cell.
PMID- 23153905
TI - Evidence for pituitary adenylate cyclase-activating peptide as a direct
immunoregulator in teleost head kidney.
AB - In mammals, pituitary adenylate cyclase activating polypeptide (PACAP) is a
potent anti-inflammatory factor, showing that it inhibits the expression and
release of proinflammatory cytokines and enhances the production of anti
inflammatory factors. However, whether fish PACAP plays similar regulatory roles
as seen in mammals remains unclear. In the present study, expression of PACAP
specific receptor PAC1-R was shown in grass carp head kidney and spleen,
supporting that PACAP may have a direct effect on fish immune cells. To test this
hypothesis, the immunoregulatory role of grass carp PACAP (gcPACAP) was examined
in head kidney leucocytes (HKLs). Results showed that gcPACAP inhibited basal and
further attenuated lipopolysaccharide (LPS)-stimulated cell viability of HKLs,
indicating that gcPACAP may possess similar inhibitory property at cellular level
as seen in mammals. Curiously, in vitro and in vivo studies revealed that gcPACAP
stimulated proinflammatory factors (IL-1beta and TNF-alpha) but not IL-10 mRNA
expression in HKLs and head kidney. Moreover, bacterial infection and LPS
enhanced IL-1beta, TNF-alpha and IL-10 mRNA expression in grass carp head kidney
and HKLs, respectively, and these stimulatory effects were not influenced by
gcPACAP. These findings suggest that PACAP plays distinct roles, at least does
not function as an anti-inflammatory factor, in fish compared with that in
mammals.
PMID- 23153906
TI - Coronary flow reserve during dipyridamole stress echocardiography predicts
mortality.
AB - OBJECTIVES: The goal of this study was to evaluate the ability of coronary flow
reserve (CFR) over regional wall motion to predict mortality in patients with
known or suspected coronary artery disease (CAD). BACKGROUND: CFR evaluated using
pulsed Doppler echocardiography testing on left anterior descending artery is the
state-of-the-art method during vasodilatory stress echocardiography. METHODS: In
a prospective, multicenter, observational study, we evaluated 4,313 patients
(2,532 men; mean age 65 +/- 11 years) with known (n = 1,547) or suspected (n =
2,766) CAD who underwent high-dose dipyridamole (0.84 mg/kg over 6 min) stress
echocardiography with CFR evaluation of left coronary descending artery (LAD) by
Doppler. Overall mortality was the only endpoint analyzed. RESULTS: Stress
echocardiography was positive for ischemia in 765 (18%) patients. Mean CFR was
2.35 +/- 0.68. At individual patient analysis, 1,419 (33%) individuals had CFR
<=2. During a median follow-up of 19 months (1st quartile 8; 3rd quartile 36),
146 patients died. The 4-year mortality was markedly higher in subjects with CFR
<=2 than in those with CFR >2, both considering the group with ischemia (39% vs.
7%; p < 0.0001) and the group without ischemia at stress echocardiography (12%
vs. 3%; p < 0.0001). At multivariable analysis, CFR on LAD <=2 (hazard ratio
[HR]: 3.31; 95% confidence interval [CI]: 2.29 to 4.78; p < 0.0001), ischemia at
stress echocardiography (HR: 2.40, 95% CI: 1.65 to 3.48, p < 0.0001), left bundle
branch block (HR: 2.26, 95% CI: 1.50 to 3.41; p < 0.0001), age (HR: 1.08, 95% CI:
1.06-1.10; p < 0.0001), resting wall motion score index (HR: 3.52, 95% CI: 2.38
to 5.21; p < 0.0001), male sex (HR: 1.74, 95% CI: 1.12 to 2.52; p = 0.003), and
diabetes mellitus (HR: 1.47, 95% CI: 1.03 to 2.08; p = 0.03) were independent
predictors of mortality. CONCLUSIONS: CFR on LAD is a strong and independent
indicator of mortality, conferring additional prognostic value over wall motion
analysis in patients with known or suspected CAD. A negative result on stress
echocardiography with a normal CFR confers an annual risk of death <1% in both
patient groups.
PMID- 23153907
TI - Coronary flow velocity reserve and survival.
PMID- 23153908
TI - Noninvasive diagnosis of ischemia-causing coronary stenosis using CT angiography:
diagnostic value of transluminal attenuation gradient and fractional flow reserve
computed from coronary CT angiography compared to invasively measured fractional
flow reserve.
AB - OBJECTIVES: The aim of this study was to compare the diagnostic performance of
coronary computed tomography angiography (CCTA)-derived computed fractional flow
reserve (FFR(CT)) and transluminal attenuation gradient (TAG) for the diagnosis
of lesion-specific ischemia. BACKGROUND: Although CCTA is commonly used to detect
coronary artery disease (CAD), it cannot reliably assess the functional
significance of CAD. Novel technologies based on CCTA were developed to integrate
anatomical and functional assessment of CAD; however, the diagnostic performance
of these methods has never been compared. METHODS: Fifty-three consecutive
patients who underwent CCTA and coronary angiography with FFR measurement were
included. Independent core laboratories determined CAD severity by CCTA, TAG, and
FFR(CT). The TAG was defined as the linear regression coefficient between
intraluminal radiological attenuation and length from the ostium; FFR(CT) was
computed from CCTA data using computational fluid dynamics technology. RESULTS:
Among 82 vessels, 32 lesions (39%) had ischemia by invasive FFR (FFR <=0.80).
Sensitivity, specificity, positive and negative predictive values, and positive
and negative likelihood ratio of TAG (<= -0.654 HU/mm) for detection of ischemia
were 38%, 88%, 67%, 69%, 3.13, and 0.71, respectively; and those of FFR(CT) were
81%, 94%, 90%, 89%, 13.54, and 0.20, respectively. Receiver-operating
characteristic curve analysis showed a significantly larger area under the curve
(AUC) for FFR(CT) (0.94) compared to that for TAG (0.63, p < 0.001) and CCTA
stenosis (0.73, p < 0.001). In vessels with noncalcified plaque or partially
calcified plaque, FFR(CT) showed a larger AUC (0.94) compared to that of TAG
(0.63, p < 0.001) or CCTA stenosis (0.70, p < 0.001). In vessels with calcified
plaque, AUC of FFR(CT) (0.92) was not statistically larger than that of TAG
(0.75, p = 0.168) or CCTA stenosis (0.80, p = 0.195). CONCLUSIONS: Noninvasive
FFR computed from CCTA provides better diagnostic performance for the diagnosis
of lesion-specific ischemia compared to CCTA stenosis and TAG.
PMID- 23153909
TI - Combined CT coronary angiography and stress myocardial perfusion imaging for
hemodynamically significant stenoses in patients with suspected coronary artery
disease: a comparison with fractional flow reserve.
AB - OBJECTIVES: We sought to determine the accuracy of combined coronary computed
tomography angiography (CTA) and computed tomography stress myocardial perfusion
imaging (CTP) in the detection of hemodynamically significant stenoses using
fractional flow reserve (FFR) as a reference standard in patients with suspected
coronary artery disease. BACKGROUND: CTP can be qualitatively assessed by visual
interpretation or quantified by the transmural perfusion ratio determined as the
ratio of subendocardial to subepicardial contrast attenuation. The incremental
value of each technique in addition to coronary CTA to detect hemodynamically
significant stenoses is not known. METHODS: Forty symptomatic patients underwent
FFR and 320-detector computed tomography assessment including coronary CTA and
CTP. Myocardial perfusion was assessed using the transmural perfusion ratio and
visual perfusion assessment. Computed tomography images were assessed by
consensus of 2 observers. Transmural perfusion ratio <0.99 was used as the
threshold for abnormal perfusion. FFR <=0.8 indicated hemodynamically significant
stenoses. RESULTS: Coronary CTA detected FFR-significant stenoses with 95%
sensitivity and 78% specificity. The additional use of visual perfusion
assessment and the transmural perfusion ratio both increased the specificity to
95%, with sensitivity of 87% and 71%, respectively. The area under the receiver
operating characteristic curve for coronary CTA + visual perfusion assessment was
significantly higher than both coronary CTA (0.93 vs. 0.85, p = 0.0003) and
coronary CTA + the transmural perfusion ratio (0.93 vs. 0.79, p = 0.0003). Per
vessel and per-patient accuracy for coronary CTA, coronary CTA + the transmural
perfusion ratio, and coronary CTA + visual perfusion assessment was 83% and 83%,
87% and 92%, and 92% and 95%, respectively. CONCLUSIONS: In suspected coronary
artery disease, combined coronary CTA + CTP identifies patients with
hemodynamically significant stenoses with >90% accuracy compared with FFR. When
interpreted with coronary CTA, visual perfusion assessment provided superior
incremental value in the detection of FFR-significant stenoses compared with the
quantitative transmural perfusion ratio assessment.
PMID- 23153910
TI - The one-stop shop offering both coronary anatomy and myocardial perfusion: may
well be opening soon, around the corner.
PMID- 23153912
TI - Are trabeculae and papillary muscles an integral part of cardiac anatomy: or
annoying features to exclude while tracing endocardial boundaries?
PMID- 23153911
TI - Correlation of trabeculae and papillary muscles with clinical and cardiac
characteristics and impact on CMR measures of LV anatomy and function.
AB - OBJECTIVES: The goal of this study was to assess the relationship of left
ventricular (LV) trabeculae and papillary muscles (TPM) with clinical
characteristics in a community-based, free-living adult cohort and to determine
the effect of TPM on quantitative measures of LV volume, mass, and ejection
fraction (EF). BACKGROUND: Hypertrabeculation has been associated with adverse
cardiovascular events, but the distribution and clinical correlates of the volume
and mass of the TPM in a normal left ventricle have not been well characterized.
METHODS: Short-axis cine cardiac magnetic resonance images, obtained using a
steady-state free precession sequence from 1,494 members of the Framingham Heart
Study Offspring cohort, were analyzed with software that automatically segments
TPM. Absolute TPM volume, TPM as a fraction of end-diastolic volume (EDV)
(TPM/EDV), and TPM mass as a fraction of LV mass were determined in all offspring
and in a referent group of offspring free of clinical cardiovascular disease and
hypertension. RESULTS: In the referent group (mean age 61 +/- 9 years; 262 men
and 423 women), mean TPM was 23 +/- 3% of LV EDV in both sexes (p = 0.9). TPM/EDV
decreased with age (p < 0.02) but was not associated with body mass index. TPM
mass as a fraction of LV mass was inversely correlated with age (p < 0.0001),
body mass index (p < 0.018), and systolic blood pressure (p < 0.0001). Among all
1,494 participants (699 men), LV volumes decreased 23%, LV mass increased 28%,
and EF increased by 7.5 EF units (p < 0.0001) when TPM were considered myocardial
mass rather than part of the LV blood pool. CONCLUSIONS: Global cardiac magnetic
resonance LV parameters were significantly affected by whether TPM was considered
as part of the LV blood pool or as part of LV mass. Our cross-sectional data from
a healthy referent group of adults free of clinical cardiovascular disease
demonstrated that TPM/EDV decreases with increasing age in both sexes but is not
related to hypertension or obesity.
PMID- 23153914
TI - Influence of ejection fraction on the prognostic value of sympathetic innervation
imaging with iodine-123 MIBG in heart failure.
AB - OBJECTIVES: The aim of this study was to determine whether left ventricular
ejection fraction (LVEF) influences the relationship between abnormal myocardial
sympathetic innervation imaging by iodine 123 meta-iodobenzylguanidine ((123)I
mIBG) and outcomes in patients with heart failure (HF). BACKGROUND: In systolic
HF, both abnormal (123)I-mIBG imaging and reduced LVEF are associated with higher
risk of cardiovascular events. Whether (123)I-mIBG imaging has the same
predictive value across the LVEF spectrum is unclear. METHODS: Among 985 patients
in the ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart
Failure) trial with New York Heart Association functional class II or III HF and
site-reported LVEF <=35%, the core laboratory-determined LVEFs were available for
901 subjects, ranging from 20% to 58% (mean LVEF 34 +/- 7%), and was >35% in 386
subjects. RESULTS: The mean age of the study population was 62 +/- 12 years, 80%
were male, and the majority had New York Heart Association functional class II
symptoms and HF of nonischemic etiology. At all levels of LVEF, the (123)I-mIBG
heart-to-mediastinum ratio of <1.6 was associated with a higher risk of death or
potentially lethal arrhythmic event and of the composite of cardiovascular death,
arrhythmic event, and HF progression. Comparing subjects with LVEF <=35% and
>35%, there was no evidence of effect modification of LVEF on the risk associated
with low heart-to-mediastinum ratio for death or arrhythmic event (adjusted
hazard ratio: 2.39 [95% confidence interval (CI): 1.03 to 5.55] vs. 5.28 [95% CI:
1.21 to 23.02]; interaction p = 0.48) and for the composite (adjusted hazard
ratio: 1.80 [95% CI: 1.01 to 3.23] vs. 2.41 [95% CI: 1.11 to 5.23]; interaction;
p = 0.86). For death or arrhythmic event, the heart-to-mediastinum ratio appeared
to improve the risk discrimination beyond clinical and biomarker data among both
LVEF groups, with improvement in the model C-statistic (0.67 vs. 0.69, p = 0.03)
and integrated discrimination improvement (p = 0.0008). CONCLUSIONS: (123)I-mIBG
imaging has prognostic value across a spectrum of LVEFs. Further studies may be
warranted to prospectively test the prognostic value of (123)I-mIBG imaging in
patients with HF and an LVEF >35%.
PMID- 23153913
TI - Selective factor XIIa inhibition attenuates silent brain ischemia: application of
molecular imaging targeting coagulation pathway.
AB - OBJECTIVES: The purpose of this study was use molecular imaging targeting
coagulation pathway and inflammation to better understand the pathophysiology of
silent brain ischemia (SBI) and monitor the effects of factor XIIa inhibition.
BACKGROUND: SBI can be observed in patients who undergo invasive vascular
procedures. Unlike acute stroke, the diffuse nature of SBI and its less tangible
clinical symptoms make this disease difficult to diagnose and treat. METHODS: We
induced SBI in mice by intra-arterial injection of fluorescently labeled
microbeads or fractionated clot into the carotid artery. After SBI induction,
diffusion-weighted magnetic resonance imaging was performed to confirm the
presence of microinfarcts in asymptomatic mice. Molecular imaging targeting the
downstream factor XIII activity (single-photon emission computed
tomography/computed tomography) at 3 h and myeloperoxidase activity (magnetic
resonance imaging) on day 3 after SBI induction were performed, without and with
the intravenous administration of a recombinant selective factor XIIa inhibitor
derived from the hematophagous insect Triatoma infestans (rHA-Infestin-4).
Statistical comparisons between 2 groups were evaluated by the Student t test or
Mann-Whitney U test. RESULTS: In SBI-induced mice, we found abnormal activation
of the coagulation cascade (factor XIII activity) and increased inflammation
(myeloperoxidase activity) close to where emboli lodge in the brain. rHA-Infestin
4 administration significantly reduced ischemic damage (53% to 85% reduction of
infarct volume, p < 0.05) and pathological coagulation (35% to 39% reduction of
factor XIII activity, p < 0.05) without increasing hemorrhagic frequency.
Myeloperoxidase activity, when normalized to the infarct volume, did not
significantly change with rHA-Infestin-4 treatment, suggesting that this
treatment does not further decrease inflammation other than that resulting from
the reduction in infarct volume. CONCLUSIONS: Focal intracerebral clotting and
inflammatory activity are part of the pathophysiology underlying SBI. Inhibiting
factor XIIa with rHA-Infestin-4 may present a safe and effective treatment to
decrease the morbidity of SBI.
PMID- 23153915
TI - Quantitative and qualitative changes in DES-related neointimal tissue based on
serial OCT.
AB - OBJECTIVES: The study evaluated serial quantitative and qualitative changes in
vascular responses to drug-eluting stents (DES) using optical coherence
tomography (OCT). BACKGROUND: Serial changes in stent strut coverage and
neointima characteristics in DES-treated lesions have not been sufficiently
investigated using OCT. METHODS: Serial OCT was performed in 72 patients with 76
DES-treated lesions at 9 months and 2 years after DES implantation (sirolimus
eluting stent, n = 23; paclitaxel-eluting stent, n = 20; zotarolimus-eluting
stent, n = 25; everolimus-eluting stent, n = 8). Serial changes in quantitative
parameters (neointimal thickness, stent strut coverage, and apposition at each
strut) and qualitative characteristics of the neointima were evaluated. RESULTS:
Mean neointimal thickness significantly increased from 164 MUm to 214 MUm between
9 months and 2 years (p < 0.001), and the percentage of uncovered stent struts
significantly decreased (from 4.4% to 2.3%, p < 0.001). Completely covered
lesions were more frequently observed at 2 years (44.7% vs. 59.2%, p = 0.07).
However, the percentage of malapposed struts (0.6% vs. 0.9%, p = 0.24) and
incidence of intracoronary thrombi (10.5% vs. 9.2%, p > 0.99) were similar. On
qualitative evaluation of neointimal morphology, lipid-laden neointima (27.6% vs.
14.5%, p = 0.009) and thin-cap neoatheroma (13.2% vs. 3.9%, p = 0.07) were more
frequently detected at 2-year follow-up compared with 9 months. In matched cross
sectional evaluation, the change of neointimal morphology from homogeneous to
heterogeneous or lipid-laden pattern was observed in 23 (30.3%) of 76 lesions.
There was a significant increase in percent neointimal hyperplasia cross
sectional area in those lesions. CONCLUSIONS: This OCT study suggested that
neointimal coverage improved from 9 months to 2 years without significant changes
in the incidence of malapposed struts and intracoronary thrombus. Additionally,
in-stent neoatherosclerosis including transformation to lipid-laden neointima
might progress during extended follow-up periods after DES implantation.
PMID- 23153916
TI - OCT-verified peri-strut low-intensity areas and the extent of neointimal
formation after 3 years following stent implantation.
PMID- 23153917
TI - Quantitative assessment of mitral regurgitation: how best to do it.
AB - Decisions regarding surgery for mitral regurgitation (MR) are predicated on the
accurate quantification of MR severity. Quantitative parameters, including vena
contracta width, regurgitant volume and fraction, and effective regurgitant
orifice area have prognostic significance and are recommended to be obtained from
patients with more than mild MR. New tools for MR quantification have been
provided by 3-dimensional echocardiography, cardiac magnetic resonance, and
cardiac computed tomography, but limited guidance on appropriate image
acquisition and post-processing techniques has hindered their clinical
application and reproducibility. This review describes optimal image acquisition
and post-processing methods for quantification of MR.
PMID- 23153918
TI - Enface reconstruction of VSD on RV septal surface using real-time 3D
echocardiography.
PMID- 23153919
TI - Delayed plaque enhancement by CT angiography.
PMID- 23153920
TI - Pre-dismissal surveillance echocardiography second day after TAVR.
PMID- 23153921
TI - Effective dose of PET/CT in informed consent forms.
PMID- 23153923
TI - Intraplaque hemorrhage, RBC-derived cholesterol, and plaque progression: time to
move from conjecture to evidence?
PMID- 23153924
TI - On tests, times, and the test of time...
PMID- 23153925
TI - Immunomodulatory drugs: new options for the treatment of myelodysplastic
syndromes.
AB - BACKGROUND: Myelodysplastic syndromes (MDS) are common adult hematologic
disorders characterized by ineffective hematopoiesis with progressive cytopenia
and a risk of evolving into currently incurable acute myeloid leukemia. Until
recently, the only treatment was bone marrow transplantation, but, over the past
few years, a new therapeutic approach based on immunomodulatory drugs (IMiD) has
been developed. IMiDs belong to a therapeutic class whose progenitor is
thalidomide, a synthetic derivative of glutamate that was initially used because
of its sedative and antiemetic properties but was then withdrawn because of its
teratogenic effects. IMiDs represent a major advance in the treatment of multiple
myeloma at different disease stages, 5q minus syndrome, acute myeloid leukemia
with the 5q deletion, mantle cell lymphoma, relapsing or unresponsive high-grade
lymphoma, and relapsing indolent lymphoma. METHODS: Medical databases and
conference proceedings were searched to identify articles and clinical trials
that have investigated or are investigating the use of IMiDs on MDS. RESULTS AND
DISCUSSION: An important part of their in vivo efficacy is attributed to their
immunomodulatory properties because they potentiate the immune response by
restoring dendritic cell function and inhibiting T-cell regulatory activity,
which leads to the activation of T lymphocytes and natural killer T cells by
increasing the production of interleukin-2 and interferon gamma. IMiDs are
characterized by antitumoral and antiangiogenic activities, and they also induce
the apoptosis of neoplastic cells. Thalidomide and its derivative lenalidomide
have been proposed for the treatment of MDS because of their action on the immune
mechanisms that appear to play an important role in the pathophysiology of this
syndrome. CONCLUSIONS: This article examines the pharmacology and molecular
action of IMiDs and the evidence of their efficacy in treating patients with MDS
in different risk classes.
PMID- 23153926
TI - Cost-effectiveness of vascular access for haemodialysis: arteriovenous fistulas
versus arteriovenous grafts.
AB - BACKGROUND: The use of an arteriovenous fistula (AVF) for haemodialysis treatment
may be associated with a high early failure rate, but usually good long-term
patency, while using an arteriovenous graft (AVG) yields a lower early failure
rate with worse long-term patency. The aim of this study was to calculate and
compare the costs and outcome of AVF and AVG surgery in terms of early and long
term patencies. METHODS: A decision tree and a Markov model were constructed to
calculate costs and performance of AVFs and AVGs. The model was populated with a
retrospective cohort of HD patients receiving their first VA. The outcomes were
determined probabilistically with a 5-year follow-up. RESULTS: AVFs were usable
for a mean (95% CI) of 28.5 months (24.6-32.5 months), while AVGs showed a
patency of 25.5 months (20.0-31.2 months). The use of AVFs was the dominant type
of VA and ? 631 could be saved per patient/per month patency compared to AVG use.
Regardless of the willingness to pay, the use of AVFs yielded a higher
probability of being cost-effective compared to AVGs. CONCLUSIONS: AVFs are more
cost-effective than AVGs. Nonetheless, early failure rates significantly
influence AVF performance and initiatives to reduce early failure can improve its
cost-effectiveness.
PMID- 23153927
TI - Copper ion-stimulated McoA-laccase production and enzyme characterization in
Proteus hauseri ZMd44.
AB - The novel bioelectricity-generating bacterium of Proteus hauseri ZMd44 has been
first identified to produce McoA-laccase (EC 1.10.3.2) induced by copper
sulphate. The optimal concentration of copper is 3 mM as supplementation at the
beginning of culture or early exponential growth phase, during which laccase is
predominantly synthesized. Moreover, the whole cellular and intracellular
activities of laccase increase in the degrees of inducible copper concentrations.
A possible mechanism for this phenomenon is that copper ions enhance the laccase
genetic transcription level during the laccase synthesis thus granting this
strain in copper tolerance. McoA-laccase belongs to typical type 1 (T1) Cu site
laccase by electron paramagnetic resonance (EPR) analysis of intracellular
enzyme. From our results, the optimal temperature and pH are 60 degrees C and pH
2.2, respectively. The kinetic profiles show that this enzyme is stable under 50
degrees C and in the slightly acidic environment, making it a potentially useful
enzyme in dye decolorization, paper-pulp bleaching and bioremediation industries.
PMID- 23153928
TI - Downregulation of extracellular signal-regulated kinase 1/2 activity by
calmodulin KII modulates p21Cip1 levels and survival of immortalized lymphocytes
from Alzheimer's disease patients.
AB - Previously, we reported a Ca(2+)/calmodulin (CaM)-dependent impairment of
apoptosis induced by serum deprivation in Alzheimer's disease (AD) lymphoblasts.
These cell lines showed downregulation of extracellular signal-regulated kinase
(ERK)1/2 activity and elevated content of p21 compared with control cells. The
aim of this study was to delineate the molecular mechanism underlying the
distinct regulation of p21 content in AD cells. Quantitative reverse
transcription polymerase chain reaction analysis demonstrated increased p21
messenger RNA (mRNA) levels in AD cells. The ERK1/2 inhibitor, PD98059, prevented
death of control cells and enhanced p21 mRNA and protein levels. The CaM
antagonist, calmidazolium, and the CaMKII inhibitor, KN-62, normalized the
survival pattern of AD lymphoblasts by augmenting ERK1/2 activation and reducing
p21 mRNA and protein levels. Upregulation of p21 transcription in AD cells
appears to be the consequence of increased activity of forkhead box O3a (FOXO3a)
as the result of diminished ERK1/2-mediated phosphorylation of this transcription
factor, which in turn facilitates its nuclear accumulation. Murine double minute
2 (MDM2) protein levels were decreased in AD cells relative to control
lymphoblasts, suggesting an impairment of FOXO3a degradation.
PMID- 23153929
TI - Supportive evidence for 11 loci from genome-wide association studies in
Parkinson's disease.
AB - Genome-wide association studies have identified a number of susceptibility loci
in sporadic Parkinson's disease (PD). Recent larger studies and meta-analyses
have greatly expanded the list of proposed association signals. We performed a
case-control replication study in a Scandinavian population, analyzing samples
from 1345 unrelated PD patients and 1225 control subjects collected by
collaborating centers in Norway and Sweden. Single-nucleotide polymorphisms
representing 18 loci previously reported at genome-wide significance levels were
genotyped, as well as 4 near-significant, suggestive, loci. We replicated 11
association signals at p < 0.05 (SNCA, STK39, MAPT, GPNMB, CCDC62/HIP1R, SYT11,
GAK, STX1B, MCCC1/LAMP3, ACMSD, and FGF20). The more recently nominated
susceptibility loci were well represented among our positive findings, including
3 which have not previously been validated in independent studies. Conversely,
some of the more well-established loci failed to replicate. While future meta
analyses should corroborate disease associations further on the level of common
markers, efforts to pinpoint functional variants and understand the biological
implications of each risk locus in PD are also warranted.
PMID- 23153930
TI - New political party will target prime minister and five others implicated in NHS
changes.
PMID- 23153931
TI - The competitive NMDA receptor antagonist CPP disrupts cocaine-induced conditioned
place preference, but spares behavioral sensitization.
AB - Recently, the notion that memory and addiction share similar neural substrates
has become widely accepted. N-methyl-d-aspartate receptors (NMDAR) are the
cornerstones of synaptic models of memory. The present study examined the effect
of the competitive NMDAR antagonist CPP on the induction of behavioral
sensitization and conditioned place preference to cocaine. Conditioned place
preference is an associative memory model of drug seeking, while sensitization is
a non-associative model of the transition from casual to compulsive use. There
were three principal findings: (1) co-administration of CPP and cocaine altered
the acute response to cocaine, suggesting a direct interaction between the two
drugs; (2) NMDAR antagonism had no effect on behavioral sensitization; and (3)
NMDAR antagonism abolished conditioned place preference. A review of prior
evidence supporting a role for NMDARs in sensitization suggests that NMDAR
antagonists directly interfere with cocaine's psychostimulant effects, and this
interaction could be misinterpreted as a disruption of sensitization. Finally, we
suggest that addiction recruits multiple kinds of plasticity, with sensitization
recruiting NMDAR-independent mechanisms.
PMID- 23153932
TI - Diagnosing autism in neurobiological research studies.
AB - Autism spectrum disorder (ASD) is by definition a complex and heterogeneous
disorder. Variation in factors such as developmental level, language ability and
IQ further complicate the presentation of symptoms. Clinical research and basic
science must continue to inform each other's questions to help address the
heterogeneity inherent to the disorder. This review uses a clinical perspective
to outline the common tools and best practices for diagnosing and characterizing
ASD in a research setting. We discuss considerations for classifying research
populations, including language ability and IQ and examine the advantages and
disadvantages of different psychometric measurements. Ultimately, the
contribution of multiple sources of data representing different perspectives is
crucial for interpreting and understanding the ASD phenotype.
PMID- 23153933
TI - An antiprogestin, CDB4124, blocks progesterone's attenuation of the negative
effects of a mild stress on sexual behavior.
AB - These experiments were designed to test the hypothesis that a progesterone
receptor antagonist would block progesterone's ability to reduce the negative
effects of a 5 min restraint on female rat sexual behavior. Ovariectomized
Fischer rats were injected with 10 MUg estradiol benzoate. Two days later, rats
were injected subcutaneously (sc) with the progesterone receptor antagonist,
CDB4124 (17alpha-acetoxy-21-methoxy-11beta-[4-N,N-dimethyaminopheny]-19-norpregna
4,9-dione-3,20-dione) (60 mg/kg), or vehicle (20% DMSO+propylene glycol). One
hour later, rats were injected sc with 500 MUg progesterone or vehicle (sesame
seed oil). Rats were assigned to one of three different treatment conditions: (1)
(ECV) estradiol benzoate, CDB4124, sesame seed oil vehicle, (2) (ECP) estradiol
benzoate, CDB4124, progesterone, and (3) (EVP) estradiol benzoate, DMSO/propylene
glycol vehicle, progesterone. That afternoon sexual behavior was examined before
and after a 5 min restraint experience. Before restraint, lordosis behavior was
comparable across treatment conditions but only progesterone-treated rats
exhibited proceptive behavior. CDB4124 did not block progesterone's induction of
proceptivity. However, after restraint, CDB4124 attenuated the positive effects
of progesterone on all sexual behaviors examined. The restraint experience
inhibited sexual behavior in rats treated with estradiol benzoate and CDB4124 and
in rats treated with estradiol benzoate, CDB4124, and progesterone but not in
rats given estradiol benzoate and progesterone without CDB4124. These findings
are consistent with the hypothesis that progesterone receptors mediate
progesterone's ability to reduce the negative sexual behavioral effects of a mild
stressor.
PMID- 23153935
TI - Robotic partial nephrectomy for solitary kidney: a multi-institutional analysis.
AB - OBJECTIVE: To evaluate the outcomes of robotic partial nephrectomy (RPN) for
solitary kidney in a large multicenter series. MATERIALS AND METHODS: Medical
records of 886 consecutive patients who underwent RPN at 5 academic institutions
from May 2007 to May 2012 were retrospectively analyzed. Data were prospectively
collected in an Investigational Review Board-approved protocol. Experienced
robotic surgeons performed all operations. Patient demographics, functional,
perioperative, and early oncologic outcomes were analyzed. RESULTS: A total of 26
patients with a solitary kidney were identified and included in the analysis; of
these, 16 (62%) had solitary kidneys secondary to a previous malignancy.
Perioperative outcomes included a median warm ischemia time of 17 minutes
(interquartile range, 12, 28 minutes). Only 2 intraoperative complications
occurred. One was a renal vein injury and one an aortic vessel tear, and both
patients required intraoperative blood transfusions. No conversions to
laparoscopy or open surgery occurred. There were 3 postoperative complications
(11.5%). Median follow-up was 6 months (interquartile range, 5, 9.7 months).
Postoperative renal function did not change significantly as measure by estimated
glomerular filtration rate (-15.8%; P=.13). None of the patients required
dialysis. Positive margins occurred in 1 patient, with 73% of patients having a
renal cell carcinoma. CONCLUSION: We report a multi-institutional series of RPN
in patients with solitary kidney presenting with small renal masses. Our findings
suggest that RPN represents a feasible treatment option in this specific
population by offering reliable preservation of renal function, low surgical
morbidity, and early oncologic safety in the hands of experienced robotic
surgeons.
PMID- 23153934
TI - Probability of downsizing primary tumors of renal cell carcinoma by targeted
therapies is related to size at presentation.
AB - OBJECTIVE: To evaluate the probability of downsizing primary renal tumors by
targeted therapy in correlation to size. METHODS: A literature search was
conducted and our own data were pooled with data of retrospective series and
prospective trials in which patients were treated with tyrosine kinase inhibitors
(TKIs) and in which tumor sizes before and after treatment were reported.
Included were 89 primary clear cell renal tumors, including 34 from our
institutes. The longest diameter of the primary tumors before and after treatment
was obtained. Primary tumor size at presentation was divided in 4 categories: <5
cm (n=10), 5 to 7 cm (n=21), 7 to 10 cm (n=31), and >10 cm (n=27). Pearson
correlation and t test were used for statistical analysis. RESULTS: The TKI was
sorafenib in 21 tumors and sunitinib in the remaining 68. Smaller tumor size was
related to more effective downsizing (P=0.01). Median downsizing was 32% (-46% to
11%) in the first group (<5 cm) and 11% (-55% to 16%) in the second group (5-7
cm); however, 8 of 21 (38%) in this group reduced to a range of 2.3 to 4.7 cm in
which ablative techniques are feasible and nephron-sparing surgery may benefit
from the reduced size. Median downsizing was 18% (-39% to 2%) in tumors of 7 to
10 cm and 10% (-31% to 0%) in those>10 cm. CONCLUSION: The smaller the primary
tumor, the greater the likelihood and the more effective the downsizing. A
potential benefit of neoadjuvant treatment to downsize the primary tumor for
ablative techniques or nephron-sparing surgery may exist, particularly in tumors
sized 5 to 7 cm.
PMID- 23153936
TI - Occurrence of dysplasia and human papilloma virus typing in penile condylomas.
AB - OBJECTIVE: To determine the incidence of dysplasia as a preneoplastic change and
high-risk human papilloma virus (HPV) infection in penile condylomas, which are
common HPV-related lesions and considered a risk factor for penile cancer.
METHODS: Histologic analysis was done of 58 consecutive penile condylomas with
tissue diagnosis. An immunohistochemical panel that included stains for p53, Ki
67, and p16INK4a was also used. HPV typing was successfully performed in 43
lesions. Genotyping was accomplished through polymerase chain reaction and flow
through hybridization with an HPV GenoArray Diagnostic Test kit. RESULTS:
Dysplasia was observed in 13 of the 58 condylomas (22%). High-risk HPV DNA was
detected in 5 of 10 dysplastic lesions (50%) for which tissue blocks were
available for study. High-risk HPV was not detected in the nondysplastic lesions
(P<.001). Ki-67>=20% above the basal layer of epithelium and p53-positive
immunostaining occurred more frequently in dysplastic lesions than in
nondysplastic lesions; however, the difference was not statistically
significance. Staining for p16INK4a was not helpful. CONCLUSION: Anogenital
condylomas in men are usually treated using destructive methods or with
medication. We suggest that at least a part of the lesion must be removed and
sent for histopathologic examination. If the histologic result shows significant
dysplastic alteration, the lesion should be further investigated to determine the
subtype of infective virus, because 50% of such lesions are associated with high
risk HPV. When oncogenic pathogens are found, careful patient follow-up for
recurrences and counseling for the patient and his sexual partner(s) may be
warranted.
PMID- 23153937
TI - Solid testicular mass in a 63-year-old man.
PMID- 23153938
TI - Effect of diabetes on the ion pumps of the bladder.
AB - OBJECTIVE: To establish whether the activities of Na+/K+-adenosine triphosphatase
(ATPase) and Ca2+-ATPases ion pumps in bladder smooth muscle are altered as a
consequence of diabetes and, if so, how this might contribute to bladder
cystopathy. Urinary bladder dysfunction is a common occurrence in patients with
diabetes. Pressure generation requires calcium and cytosolic ATP. Activities of
these pumps are responsible for calcium homeostasis. METHODS: Rat urinary
detrusor muscle strips were suspended in organ baths containing Krebs solution
for isometric tension recording. Tissue responses to the Na+/K+-ATPase pump
inhibitor, ouabain, the plasma membrane Ca2+ ATPase inhibitor, vanadate, and the
sarcoplasmic reticulum Ca2+ ATPase inhibitor, cyclopiazonic acid (CPA), were
examined from normal and streptozocin-induced diabetic rats for 2, 4, and 12
weeks. RESULTS: Ouabain, vanadate, and CPA caused concentration-dependent
contractions of bladder strips from diabetic and normal rats. The degree of
contraction of diabetic bladder muscle was lower than that of controls. This
reduction was a function of duration of diabetes. For ouabain, the reduction
peaked at 2 weeks, with partial restoration to normal after diabetes induction.
For vanadate and CPA, the reduction increased with the duration of diabetes.
CONCLUSION: The ion pumps are important modulators of bladder smooth muscle tone,
and in a rat model of streptozotocin-induced diabetes, the activity of these
pumps is impaired. Although this is only a single model of diabetes, these
findings suggest that a defect in these pumps may be an important component of
the development of diabetic bladder cystopathy.
PMID- 23153939
TI - Inducing cell proliferation inhibition, apoptosis, and motility reduction by
silencing long noncoding ribonucleic acid metastasis-associated lung
adenocarcinoma transcript 1 in urothelial carcinoma of the bladder.
AB - OBJECTIVE: To study the expression patterns of long noncoding ribonucleic acid
(RNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and the
cell proliferation inhibition, apoptosis, and motility changes induced by
silencing MALAT1 in urothelial carcinoma of the bladder. MATERIALS AND METHODS:
The expression levels of MALAT1 were determined using real-time quantitative
polymerase chain reaction in cancerous tissues and paired normal tissues in a
total of 36 patients with urothelial carcinoma of the bladder. Expression
differences were analyzed according to the grade and stage. Bladder urothelial
carcinoma T24 and 5637 cells were transfected with MALAT1 small interfering RNA
or negative control small interfering RNA. The cell proliferation changes of the
transfected bladder urothelial carcinoma cells were determined using the MTT
assay. Apoptosis caused by silencing MALAT1 was evaluated using the flow
cytometry assay and enzyme-linked immunosorbent assay. The motility changes
induced by silencing MALAT1 were measured using the wound healing assay. RESULTS:
MALAT1 was upregulated in bladder urothelial carcinoma compared with matched
normal urothelium (P=.008). The MALAT1 expression levels were greater in high
grade carcinomas than in low-grade carcinoma (P=.001). The MALAT1 expression
levels were greater in invasive carcinoma than in noninvasive carcinoma (P=.018).
Cell proliferation inhibition, increased apoptosis, and decreased motility were
observed in MALAT1 small interfering RNA-transfected bladder urothelial carcinoma
T24 and 5637 cells. CONCLUSION: MALAT1 plays an oncogenic role in urothelial
carcinoma of the bladder. Silencing MALAT1 is a potential novel therapeutic
approach for this cancer.
PMID- 23153940
TI - Simvastatin suppresses cyclophosphamide-induced changes in urodynamics and
bladder inflammation.
AB - OBJECTIVE: To assess the ability of daily oral simvastatin administration to
reduce the negative urodynamic changes associated with cyclophosphamide (CP)
induced cystitis and to prevent bladder inflammation. Patients undergoing CP
chemotherapy frequently develop cystitis, leading to urinary dysfunction and
hemorrhage. Recent studies have suggested statins possess anti-inflammatory
properties and might be uroprotective. MATERIALS AND METHODS: Urodynamic
properties were analyzed in 4 groups of female Sprague-Dawley rats: group 1,
vehicle (300 MUL, 0.5% methylcellulose, orally for 7 days); group 2, simvastatin
(1 mg/rat/d); group 3, vehicle plus CP (intraperitoneally 80 mg/kg, 24 h before
cystometry); and group 4, simvastatin plus CP. The inflammation in the groups was
assessed using Evans blue extravasation. RESULTS: CP stimulated significant
increases in the number of nonvoiding contractions (0.83+/-0.26 vs 4.97+/-1.90;
P=.03) and decreases in the peak voiding pressure (53.46+/-5.08 vs 33.34+/-4.37
cm H2O; P=.01). Simvastatin returned these parameters to the control levels of
1.62+/-0.73 (P=.70) and 45.98+/-7.78 cm H2O (P=.38). CP at this level caused a
slight, but significant, increase in the voided volume (0.82+/-0.13 vs 1.16+/
0.14 mL; P=.04), which returned to control levels (0.74+/-0.12 mL; P=.65) with
simvastatin. Other urodynamic parameters, such as the threshold pressure, were
not affected by simvastatin or CP, or the combination of the 2. CP-induced
inflammation in the bladder (Evans blue extravasation) was suppressed by
simvastatin. CONCLUSION: Simvastatin was effective at ameliorating the negative
urodynamic changes and inflammation in the bladder after CP administration and is
a potential therapy for preventing side effects in patients undergoing this
chemotherapy.
PMID- 23153942
TI - Better irrigation delivers better vision: an exploratory study of a novel
continuous irrigation sheath for a flexible cystoscope.
AB - OBJECTIVE: To evaluate the effectiveness of a novel continuous irrigation sheath
(NCIS) for improving the vision of a flexible cystoscope under gross hematuria
and to investigate whether this NCIS increases patient discomfort. METHODS: A
model was designed and a trial was conducted to quantitatively evaluate the
effectiveness of the NCIS in vitro. The trial was divided into a static and a
dynamic trial. The main difference between these two parts of the trial was the
presence of continuous hemorrhage. There were 3 levels for the irrigation
condition: no irrigation (group 1), continuous irrigation without an outflow of
water (group 2), and continuous irrigation with an outflow of water (group 3).
Flexible cystoscopy was conducted under different conditions and repeated, and
the main outcome measures, including field of flexible cystoscope's vision (FFCV)
and definition of the pictures taken by the flexible cystoscope (DFC), were
measured at 30, 60, 90 and 120 seconds. To investigate whether the NCIS increased
patient discomfort, 36 patients were randomized into 2 groups to receive flexible
cystoscopy with or without the NCIS. RESULTS: Compared with groups 1 and 2, the
FFCV and DFC values were significantly increased in group 3; however, the FFCV
was not significantly increased compared with group 2 in the static model. The
pain scores between patients who received flexible cystoscopy with or without the
NCIS did not differ significantly. CONCLUSION: The NCIS effectively improved the
vision of a flexible cystoscope without increasing patient discomfort.
PMID- 23153945
TI - Editorial comment.
PMID- 23153947
TI - Editorial comment.
PMID- 23153948
TI - Editorial comment.
PMID- 23153949
TI - Hypertension in pediatric patients with renal scarring in association with
vesicoureteral reflux.
AB - OBJECTIVE: To examine the reflux nephropathy rate and severity as well as the
hypertension rate in pediatric patients with vesicoureteral reflux (VUR).
METHODS: The study included 240 patients with VUR. Renal scarring (RS) was
demonstrated by renal parenchymal examination using technetium-99m-labeled
dimercaptosuccinic acid (99mTc-DMSA) scintigraphy. Office measurements of
arterial blood pressure and ambulatory blood pressure monitoring (ABPM) of VUR
patients were done during the follow-up period. RESULTS: Follow-up was a mean
duration of 24 months. Rates of RS and hypertension increased parallel to
increases in the degree of VUR. A gradual elevation in hypertension rates was
evident during the follow-up period. All patients with hypertension had RS.
Severe RS in 56 patients was associated with increasing blood pressure readings
by 24-hour ABPM or office measurements in 19 patients (33.9%). ABPM measurements
enabled us to detect additional patients compared with office measurements alone.
CONCLUSION: Hypertension is a serious complication in children with reflux
nephropathy and is associated with the severity of RS and VUR grade. ABPM seems
to be superior over office measurements of blood pressure in identifying patients
with hypertension.
PMID- 23153950
TI - Incidence, risk factors, and complications of postoperative delirium in elderly
patients undergoing radical cystectomy.
AB - OBJECTIVE: To identify the risk factors for, and complications associated with,
the development of delirium after radical cystectomy. MATERIALS AND METHODS: From
July 2008 to December 2009, 59 patients, aged >=65 years and undergoing radical
cystectomy, were prospectively enrolled. The baseline cognitive status was
assessed using the Mini-Mental Status Examination. Postoperative delirium was
assessed using the Confusion Assessment Method. RESULTS: A total of 49 patients
completed the surgery and all assessments. The incidence of postoperative
delirium was 29%, with duration of 1-5 days. On univariate analysis, older age
and preoperative Mini-Mental Status Examination score were associated with
postoperative delirium. On multivariate analysis, only age was associated with
postoperative delirium (odds ratio 1.52, 95% confidence interval 1.04-2.22,
P=.03). The 2 groups did not differ in pathologic stage, length of surgery,
intraoperative and postoperative narcotic usage, body mass index, age-adjusted
Charlson comorbidity index, activities of daily living scores, smoking history,
preoperative hematocrit, estimated blood loss, urinary tract infection, interval
to a regular diet, or length of hospital stay. The patients who developed
postoperative delirium were more likely to undergo readmission (odds ratio 10.7,
95% confidence interval 2.2-51.8, P=.01) and reoperation (odds ratio 9.2, 95%
confidence interval 1.5-55.3, P=.03) but did not differ in the 90-day and 1-year
mortality rates or incidence of postoperative complications. CONCLUSION: In
patients aged>=65 years, a lower preoperative Mini-Mental Status Examination
score and older age were significantly associated with the development of
postcystectomy delirium, as measured using the Confusion Assessment Method. The
patients who developed delirium were more likely to undergo readmission and
reoperation. Larger studies with multiple surgeons are needed to validate these
findings.
PMID- 23153951
TI - Contemporary urethral stricture characteristics in the developed world.
AB - OBJECTIVE: To assess the current etiology, features, and natural history of
urethral stricture disease in the developed world. MATERIALS AND METHODS: We
analyzed the data from 1439 male patients with urethral stricture, who had
undergone surgical treatment in our referral urethral center from 2000 to 2010.
The preoperative evaluation included a detailed clinical history of stricture,
uroflowmetry, retrograde and voiding cystourethrography, and urethroscopy.
Statistical analysis was done for the stricture site, length, and etiology,
patient age, and previous treatments. RESULTS: Strictures were posterior in 112
(7.8%) and anterior in 1327 (92.2%). In the anterior group, 439 were penile
(30.5%), 675 bulbar (46.9%), 71 penile plus bulbar (9.9%), and 142 panurethral
(4.9%). The main causes were iatrogenic in 556 (38.6%), unknown in 515 (35.8%),
lichen sclerosus in 193 (13.4%), and trauma in 156 (10.8%). The main iatrogenic
strictures were from catheterization in 234 (16.3%), hypospadias repair in 176
(12.2%), and transurethral surgery in 131 (9.1%). The stricture distribution
increased until about 45 years and then decreased. Strictures were uncommon in
those<20 and >70 years old. The mean length was 4.15 cm; longer strictures were
found in those with lichen sclerosus (7.45 cm) or after hypospadias repair (4.42
cm) and catheterization (4.40 cm). The mean length was also greater in the
pretreated (4.34 cm) than in the untreated (3.64 cm) strictures. CONCLUSION:
Urethral stricture in developed countries mainly involves the anterior urethra,
in particular the bulbar tract. The most common cause was iatrogenic. Hypospadias
repair and lichen sclerosus represent emerging important causes. Finally,
urethral stricture is not a disease of the elderly but involves all ages.
PMID- 23153952
TI - Knowledge and attitude of European urology residents about ionizing radiation.
AB - OBJECTIVE: To evaluate the attitude and knowledge of urology residents concerning
ionizing radiation, we undertook a survey of European urology residents. METHODS:
The questionnaire was sent to 1184 urology residents within the database of the
European Society of Residents in Urology (ESRU) by e-mail between November 2011
and January 2012. The questionnaire was composed of demographic questions and
questions about the frequency of radiation exposure and use of radiation safety
measures during fluoroscopy-guided endourologic procedures. In addition, there
were questions about education programs and respondents' knowledge about
diagnostic imaging modalities. RESULTS: A total of 124 questionnaires were
returned from urology residents in 20 different European countries. All of the
respondents reported that they were routinely exposed to ionizing radiation, and
69 (72.5%) were exposed more than 3 times per week. Despite the common but not
sufficient use of lead aprons (75%), use of other radiation protection measures
was very low. Although 55% of the respondents had attended an education program
in Europe about radiation safety, attendance was highest in Poland (82.6%). The
level of knowledge about ionizing radiation was low among urology residents, and
approximately half of responders had no idea that commonly used imaging
modalities have a fatal cancer risk. CONCLUSION: The results of this study showed
the lack of knowledge and awareness about the importance of ionizing radiation
protection among urology residents in Europe. We therefore suggest radiation
safety courses in every step of medical life for doctors, especially for
endourologists.
PMID- 23153953
TI - Protective effects of reducing renal ischemia-reperfusion injury during renal
hilar clamping: use of allopurinol as a nephroprotective agent.
AB - OBJECTIVE: To investigate the relationship between renal ischemia injury and
concentrations of 8-isoprostane in a rat kidney model during renal hilar clamping
and their correlation with the administration of allopurinol before clamping.
MATERIALS AND METHODS: Reperfusion injury occurs after the reintroduction of
blood flow after a prolonged period of ischemia. Thought to be due to oxygen free
radicals released by the endothelial, mitochondrial, and parenchymal cells, this
process leads to a cascade of events whereby infiltrative leukocytes generate
cytokines and reactive oxygen species. The present study was performed in 2
parts. Our primary objective was to first develop a method of quantitating the
renal damage using a prostaglandin compound formed in vivo, specifically
isoprostane. After the development of this animal model of quantitating renal
injury, our second objective was to apply this model and investigate
allopurinol's nephroprotective abilities. A microdialysis probe was inserted into
the renal parenchyma of rats to allow continuous dialysis and collection of the
effluent for isoprostane levels. After clamping of the renal vessels to induce
ischemia, the interstitial effluent from the probe was collected and subsequently
analyzed for 8-isoprostane levels with and without allopurinol pretreatment.
RESULTS: Clamping of the renal hilum in this rat model significantly increased 8
isoprostane levels. After 60 minutes of clamp time, the largest absolute increase
in 8-isoprostane levels resulted, representing a 3.2-fold increase from baseline.
However, the rats that had been pretreated with allopurinol demonstrated
significantly less isoprostane levels, to baseline levels. CONCLUSION:
Allopurinol has demonstrated significant benefits by reducing reperfusion injury
in rat kidneys, as demonstrated by the use of 8-isoprostane as a tool for the
real-time measurement of ischemic injury.
PMID- 23153954
TI - Laparoendoscopic single site (LESS) in vivo suturing using a magnetic anchoring
and guidance system (MAGS) camera in a porcine model: impact on ergonomics and
workload.
AB - OBJECTIVE: To compare the ergonomics and workload of the surgeon during single
site suturing while using the magnetic anchoring and guidance system (MAGS)
camera vs a conventional laparoscope. METHODS: Seven urologic surgeons were
enrolled and divided into an expert group (n=2) and a novice group (n=5)
according to their laparoendoscopic single-site (LESS) experience. Each surgeon
performed 2 conventional LESS and 2 MAGS camera-assisted LESS vesicostomy
closures in a porcine model. A Likert scale (scoring 1-5) questionnaire assessing
workload, ergonomics, technical difficulty, visualization, and needle handling,
as well as a validated National Aeronautics and Space Administration Task Load
Index (NASA-TLX) questionnaire were used to evaluate the tasks and workloads.
RESULTS: MAGS LESS suturing was universally favored by expert and novice surgeons
compared with conventional LESS in workload (3.4 vs 4.2), ergonomics (3.4 vs
4.4), technical challenge (3.3 vs 4.3), visualization (2.4 vs 3.3), and needle
handling (3.1 vs 3.9 respectively; P<.05 for all categories). Surgeon NASA-TLX
assessments found MAGS LESS suturing significantly decreased the workload in
physical demand (P=.004), temporal demand (P=.017), and effort (P=.006). External
instrument clashing was significantly reduced in MAGS LESS suturing (P<.001). The
total operative time of MAGS LESS suturing was comparable to that of conventional
LESS (P=.89). CONCLUSION: MAGS camera technology significantly decreased surgeon
workload and improved ergonomics. Nevertheless, LESS suturing and knot tying
remains a challenging task that requires training, regardless of which camera is
used.
PMID- 23153955
TI - The dietary pattern of patients with schizophrenia: a systematic review.
AB - OBJECTIVE: People with schizophrenia show a high incidence of metabolic syndrome,
which is associated with a high mortality from cardiovascular disease. The
aetiology of the metabolic syndrome in schizophrenia is multi-factorial and may
involve antipsychotic treatment, high levels of stress and unhealthy lifestyle,
such as poor diet. As a poor diet can predispose to the development of metabolic
abnormalities, the aims of this review are to clarify: 1) the dietary patterns of
patients with schizophrenia, 2) the association of these dietary patterns with a
worse metabolic profile, and 3) the possible factors influencing these dietary
patterns. METHODS: A search was conducted on Pubmed, The Cochrane Library,
Scopus, Embase, Ovid, Psychoinfo and ISI web of Knowledge from 1950 to the 1st of
November 2011. 783 articles were found through the investigation of such
databases. After title, abstract or full-text reading and applying exclusion
criteria we reviewed 31 studies on dietary patterns and their effects on
metabolic parameters in schizophrenia. RESULTS: Patients with schizophrenia have
a poor diet, mainly characterized by a high intake of saturated fat and a low
consumption of fibre and fruit. Such diet is more likely to increase the risk to
develop metabolic abnormalities. Data about possible causes of poor diet in
schizophrenia are still few and inconsistent. CONCLUSION: Subjects with
schizophrenia show a poor diet that partly accounts for their higher incidence of
metabolic abnormalities. Further studies are needed to clarify the causes of poor
diet and the role of dietary intervention to improve their physical health.
PMID- 23153956
TI - Sex of newborns associated with place and mode of delivery: a population-based
study in northern Vietnam.
AB - BACKGROUND: There is increasing evidence of an elevated sex ratio at birth (SRB)
in many Asian countries, including Vietnam, and that this prenatal gender
inequity is related to sex-selective abortion. However, few studies have
investigated the relation between the sex of offspring and delivery care
utilization. OBJECTIVE: The aim of the present study was to relate sex of
newborns to place and mode of delivery in a province in northern Vietnam.
METHODS: A population-based surveillance system within the Neonatal Health
Knowledge Into Practice (NeoKIP) project (ISRCTN44599712) recorded all births
within eight districts of Quang Ninh province in northern Vietnam from July 2008
to June 2011. RESULTS: In total, there were 22,377 live births within the study
area. SRB was 108 boys per 100 girls. There was a large difference in SRB
depending on place of delivery, with 94 boys per 100 girls being delivered at
home, whereas 113 boys per 100 girls were delivered at a district-level hospital.
Cesarean section (CS) rate was 17%, and within the CS group, the SRB was 135:100.
CONCLUSIONS: We demonstrated an elevated SRB, especially at district hospital
level, and that sex of offspring influenced place and mode of delivery. Although
mothers to boys were more likely to receive more qualified delivery care, they
were at the same time more likely to undergo unnecessary surgery. Correct
information to women and family members about CS and stricter implementation of
the medical indications for CS are urgently called for.
PMID- 23153957
TI - The high mobility group box: the ultimate utility player of a cell.
AB - High mobility group (HMG) box proteins are abundant and ubiquitous DNA binding
proteins with a remarkable array of functions throughout the cell. The structure
of the HMG box DNA binding domain and general mechanisms of DNA binding and
bending have been known for more than a decade. However, new mechanisms that
regulate HMG box protein intracellular translocation, and by which HMG box
proteins recognize DNA with and without sequence specificity, have only recently
been uncovered. This review focuses primarily on the Sry-like HMG box family,
HMGB1, and mitochondrial transcription factor A. For these proteins, structural
and biochemical studies have shown that HMG box protein modularity, interactions
with other DNA binding proteins and cellular receptors, and post-translational
modifications are key regulators of their diverse functions.
PMID- 23153959
TI - Three-dimensional imaging of collagen fibril organization in rat circumferential
lamellar bone using a dual beam electron microscope reveals ordered and
disordered sub-lamellar structures.
AB - Lamellar bone is a major component of most mammalian skeletons. A prominent
component of individual lamellae are parallel arrays of mineralized type I
collagen fibrils, organized in a plywood like motif. Here we use a dual beam
microscope and the serial surface view (SSV) method to investigate the three
dimensional collagen organization of circumferential lamellar bone from rat
tibiae after demineralization and osmium staining. Fast Fourier transform
analysis is used to quantitatively identify the mean collagen array orientations
and local collagen fibril dispersion. Based on collagen fibril array orientations
and variations in fibril dispersion, we identify 3 distinct sub-lamellar
structural motifs: a plywood-like fanning sub-lamella, a unidirectional sub
lamella and a disordered sub-lamella. We also show that the disordered sub
lamella is less mineralized than the other sub-lamellae. The hubs and junctions
of the canalicular network, which connect radially oriented canaliculi, are
intimately associated with the disordered sub-lamella. We also note considerable
variations in the proportions of these 3 sub-lamellar structural elements among
different lamellae. This new application of Serial Surface View opens the way to
quantitatively compare lamellar bone from different sources, and to clarify the 3
dimensional structures of other bone types, as well as other biological
structural materials.
PMID- 23153960
TI - The SAPHO syndrome.
AB - OBJECTIVE: To review the epidemiology, presentation, diagnosis, treatment,
pathogenesis, and genetics of the syndrome known under the acronym of SAPHO for
Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis to heighten awareness of
this entity. METHODS: We conducted a Medline search using SAPHO syndrome, chronic
recurrent multifocal osteitis/osteomyelitis, and related terms as keywords and
extracted further relevant articles from the retrieved references. RESULTS: The
SAHPO acronym identifies a syndrome encompassing a variety of osteoarticular
disorders that are frequently accompanied by dermatoses characterized by
neutrophilic pseudoabscesses, but can also occur in isolation. SAPHO syndrome is
rare, although probably underrecognized because its diagnosis may be challenging
because of the wide variability in its musculoskeletal and cutaneous
manifestations. This is especially true when atypical sites are involved and when
specific skin lesions are absent. There are no standardized treatment protocols
available. Current treatments are empirical and have the objective of providing
relief from the at times debilitating pain associated with SAPHO syndrome. They
include nonsteroidal anti-inflammatory drugs and analgesics as first-line agents.
Systemic corticosteroids, disease-modifying anti-rheumatic drugs, biologicals
targeting tumor necrosis factor alpha and interleukin-1, and bisphosphonates have
all been beneficial in some patients, but ineffective in others. This suggests
that the pathogenesis of SAPHO syndrome is multifactorial, but this aspect
remains poorly explored, although bacteria and immunological dysfunction are
hypothesized to play a role. CONCLUSIONS: The early recognition, diagnosis, and
prompt treatment of SAPHO syndrome can prevent the unnecessary use of long-term
antibiotics or invasive procedures, while rapidly alleviating pain in a majority
of affected patients.
PMID- 23153961
TI - High in vitro antimicrobial activity of beta-peptoid-peptide hybrid oligomers
against planktonic and biofilm cultures of Staphylococcus epidermidis.
AB - An array of beta-peptoid-peptide hybrid oligomers displaying different amino
acid/peptoid compositions and chain lengths was studied with respect to
antimicrobial activity against Staphylococcus epidermidis both in planktonic and
biofilm cultures, comparing the effects with those of the common antibiotic
vancomycin. Susceptibility and time-kill assays were performed to investigate
activity against planktonic cells, whilst confocal laser scanning microscopy was
used to investigate the dynamics of the activity against cells within biofilms.
All tested peptidomimetics were bactericidal against both exponentially growing
and stationary-phase S. epidermidis cells with similar killing kinetics. At the
minimum inhibitory concentration (MIC), all peptidomimetics inhibited biofilm
formation, whilst peptidomimetics at concentrations above the MIC (80-160MUg/mL)
eradicated young (6-h-old) biofilms, whilst even higher concentrations were
needed to eradicate mature (24-h-old) biofilms completely. Chiral and
guanidinylated hybrids exhibited the fastest killing effects against slow-growing
cells and had more favourable antibiofilm properties than analogues only
containing lysine or lacking chirality in the beta-peptoid residues. However, the
results of the mature biofilm killing assay indicated more complex structure
activity relationships. Cytotoxicity assays showed a clear correlation between
oligomer length and cell toxicity within each subclass of peptides, but all
possessed a high differential toxicity favouring killing of bacterial cells. This
class of peptidomimetics may constitute promising antimicrobial alternatives for
the prevention and treatment of multidrug-resistant S. epidermidis infections.
PMID- 23153958
TI - New insights into replisome fluidity during chromosome replication.
AB - Several paradigm shifting advances have recently been made on the composition and
function of the chromosomal DNA replication machinery. Replisomes appear to be
more fluid and dynamic than ever imagined, enabling rapid and efficient bypass of
roadblocks and template lesions while faithfully replicating chromosomal DNA.
This fluidity is determined by many layers of regulation, which reach beyond the
role of replisome components themselves. In fact, recent studies show that
additional polymerases, post-transcriptional modifications, and chromatin
structure are required for complete chromosome duplication. Many of these factors
are involved with the more complex events that take place during lagging-strand
synthesis. These, and other recent discoveries, are the focus of this review.
PMID- 23153962
TI - beta-Lactam therapeutic drug monitoring in the critically ill: optimising drug
exposure in patients with fluctuating renal function and hypoalbuminaemia.
AB - beta-Lactams are routinely prescribed in the treatment of serious infections.
Empirical dosing schedules are typically derived from studies in healthy
volunteers and largely fail to consider the significant changes in antibacterial
pharmacokinetics often encountered in the critically ill. These changes are
primarily driven by the underlying pathophysiology and the interventions
provided, leading to altered protein binding, poor tissue penetration, and
fluctuations in the volume of distribution and drug clearance. Each separately,
and in combination, is likely to complicate successful beta-lactam administration
in this setting. Although antibacterial therapeutic drug monitoring (TDM) has
traditionally been employed to minimise drug toxicity, the challenges to
achieving 'optimal' drug concentrations in the critically ill suggest beta-lactam
TDM as an attractive means to optimise drug exposure. Whilst there is currently
little evidence to support routine widespread application of such a service, beta
lactam TDM may still have a role in select patients where difficulty in
establishing therapeutic concentrations can be illustrated. This series utilises
three representative cases from a beta-lactam TDM service that highlight the
utility of this intervention in optimising antibacterial dosing. These
preliminary data support an expanding role for beta-lactam TDM in select
critically ill patients and provide insight into the subpopulations most at risk
of suboptimal drug exposure. Future studies investigating the clinical outcome
benefits of beta-lactam TDM in these patient groups are now warranted.
PMID- 23153963
TI - Randomised clinical trial of moxifloxacin versus ertapenem in complicated intra
abdominal infections: results of the PROMISE study.
AB - Antibiotic therapy for complicated intra-abdominal infections (cIAIs) should
provide broad-spectrum coverage both Gram-positive and Gram-negative
microorganisms. The PROMISE study compared the clinical and bacteriological
efficacy and safety of moxifloxacin versus ertapenem for the treatment of cIAIs.
This randomised, prospective, double-dummy, double-blind, multicentre trial was
designed as a non-inferiority study. The safety and efficacy of 5-14 days of
daily intravenous moxifloxacin (400mg) or ertapenem (1g) were compared in
patients with cIAIs requiring surgery and parenteral antibiotic therapy. The
primary and secondary endpoints included clinical and bacteriological responses
at 21-28 days after the end of treatment (TOC), respectively. Of 830 enrolled
patients, 699 were efficacy valid. Moxifloxacin was non-inferior to ertapenem
regarding clinical success [89.5% (315/352) versus 93.4% (324/347); 95%
confidence interval (CI) -7.9%, 0.4%]. There were no significant differences
between groups for any of the primary causes or types of cIAI regarding clinical
response. Bacteriological success was achieved in 86.5% (257/297) of moxifloxacin
treated patients and 90.2% (249/276) of ertapenem-treated patients (95% CI -9.0%,
1.5%). There were no major differences between groups regarding the frequency or
types of organisms eradicated. The incidence of adverse events (AEs) was higher
with moxifloxacin than ertapenem (P=0.039), however a similar number of drug
related AEs was seen in each group (P=1.000). Wound infections, nausea and
increased lipase were the most commonly reported AEs with both agents. The
results show that moxifloxacin is a valuable treatment option for a range of
community-acquired cIAIs with mild-to-moderate severity.
PMID- 23153964
TI - Basal ganglia-cortical interactions in Parkinsonian patients.
AB - Parkinson's disease is a common and debilitating condition, caused by aberrant
activity in a complex basal ganglia-thalamocortical circuit. Therapeutic advances
rely on characterising interactions in this circuit. However, recording
electrophysiological responses over the entire circuit is impractical. Dynamic
causal modelling offers large-scale models of predictive value based on a limited
or partial sampling of complex networks. Using dynamic causal modelling, we
determined the network changes underlying the pathological excess of beta
oscillations that characterise the Parkinsonian state. We modelled data from five
patients undergoing surgery for deep brain stimulation of more than one target.
We found that connections to and from the subthalamic nucleus were strengthened
and promoted beta synchrony, in the untreated compared to the treated
Parkinsonian state. Dynamic causal modelling was able to replicate the effects of
lesioning this nucleus and may provide a new means of directing the search for
therapeutic targets.
PMID- 23153965
TI - Identification of a strategic brain network underlying processing speed deficits
in vascular cognitive impairment.
AB - Patients with vascular cognitive impairment (VCI) commonly exhibit deficits in
processing speed. This has been attributed to a disruption of frontal-subcortical
neuronal circuits by ischemic lesions, but the exact mechanisms and underlying
anatomical structures are poorly understood. We set out to identify a strategic
brain network for processing speed by applying graph-based data-mining techniques
to MRI lesion maps from patients with small vessel disease. We studied 235
patients with CADASIL, a genetic small vessel disease causing pure VCI. Using a
probabilistic atlas in standard space we first determined the regional volumes of
white matter hyperintensities (WMH) and lacunar lesions (LL) within major white
matter tracts. Conditional dependencies between the regional lesion volumes and
processing speed were then examined using Bayesian network analysis. Exploratory
analysis identified a network of five imaging variables as the best determinant
of processing speed. The network included LL in the left anterior thalamic
radiation and the left cingulum as well as WMH in the left forceps minor, the
left parahippocampal white matter and the left corticospinal tract. Together
these variables explained 34% of the total variance in the processing speed
score. Structural equation modeling confirmed the findings obtained from the
Bayesian models. In summary, using graph-based models we identified a strategic
brain network having the highest predictive value for processing speed in our
cohort of patients with pure small vessel disease. Our findings confirm and
extend previous results showing a role of frontal-subcortical neuronal circuits,
in particular dorsolateral prefrontal and cingulate circuits, in VCI.
PMID- 23153967
TI - Single subject fMRI test-retest reliability metrics and confounding factors.
AB - While the fMRI test-retest reliability has been mainly investigated from the
point of view of group level studies, here we present analyses and results for
single-subject test-retest reliability. One important aspect of group level
reliability is that not only does it depend on between-session variance (test
retest), but also on between-subject variance. This has partly led to a debate
regarding which reliability metric to use and how different sources of noise
contribute to between-session variance. Focusing on single subject reliability
allows considering between-session only. In this study, we measured test-retest
reliability in four behavioural tasks (motor mapping, covert verb generation,
overt word repetition, and a landmark identification task) to ensure
generalisation of the results and at three levels of data processing (time-series
correlation, t value variance, and overlap of thresholded maps) to understand how
each step influences the other and how confounding factors influence reliability
at each of these steps. The contributions of confounding factors (scanner noise,
subject motion, and coregistration) were investigated using multiple regression
and relative importance analyses at each step. Finally, to achieve a fuller
picture of what constitutes a reliable task, we introduced a bootstrap technique
of within- vs. between-subject variance. Our results show that (i) scanner noise
and coregistration errors have little contribution to between-session variance
(ii) subject motion (especially correlated with the stimuli) can have detrimental
effects on reliability (iii) different tasks lead to different reliability
results. This suggests that between-session variance in fMRI is mostly caused by
the variability of underlying cognitive processes and motion correlated with the
stimuli rather than technical limitations of data processing.
PMID- 23153966
TI - The impact of visual acuity on age-related differences in neural markers of early
visual processing.
AB - The extent to which age-related differences in neural markers of visual
processing are influenced by changes in visual acuity has not been systematically
investigated. Studies often indicate that their subjects had normal or corrected
to-normal vision, but the assessment of visual acuity seems to most frequently be
based only on self-report. Consistent with prior research, to be included in the
current study, subjects had to report normal or corrected-to-normal vision.
Additionally, visual acuity was formally tested using a Snellen eye chart. Event
related potentials (ERPs) were studied in young adults (18-32years old), young
old adults (65-79years old), and old-old adults (80+ years old) while they
performed a visual processing task involving selective attention to color. Age
related differences in the latency and amplitude of ERP markers of early visual
processing, the posterior P1 and N1 components, were examined. All results were
then re-analyzed after controlling for visual acuity. We found that visual acuity
declined as a function of age. Accounting for visual acuity had an impact on
whether older and younger adults differed significantly in the size and latency
of the posterior P1 and N1 components. After controlling for visual acuity, age
related increases in P1 and N1 latency did not remain significant, and older
adults were found to have a larger P1 amplitude than young adults. Our results
suggest that until the relationship between age-associated differences in visual
acuity and early ERPs is clearly established, investigators should be cautious
when interpreting the meaning of their findings. Self-reports about visual acuity
may be inaccurate, necessitating formal measures. Additional investigation is
needed to help establish guidelines for future research, especially of very old
adults.
PMID- 23153968
TI - Expert individuation of objects increases activation in the fusiform face area of
children.
AB - The role of experience in the development of brain mechanisms for face
recognition is intensely debated. Experience with subordinate- and individual
level classification of faces is thought, by some, to be foundational in the
development of the specialization of face recognition. Studying children with
extremely intense interests (EII) provides an opportunity to examine experience
related changes in non-face object recognition in a population where face
expertise is not fully developed. Here, two groups of school-aged children -one
group with an EII with Pokemon cards and another group of age-matched controls -
underwent fMRI while viewing faces, Pokemon characters, Pokemon objects, and
Digimon characters. Pokemon objects were non-character Pokemon cards that experts
do not typically individuate during game play and trading. Neither experts nor
controls had previous experience with Digimon characters. As expected, experts
and controls showed equivalent activation in the fusiform face area (FFA) with
face stimuli. As predicted by the expertise hypothesis, experts showed greater
activation than controls with Pokemon characters, and showed greater activation
with Pokemon characters than Pokemon objects. Experts and controls showed
equivalent activation with Digimon characters. However, heightened activation
with Digimon characters in both groups suggested that there are other strong
influences on the activation of the FFA beyond stimulus characteristics,
experience, and classification level. By demonstrating the important role of
expertise, the findings are inconsistent with a purely face-specific account of
FFA function. To our knowledge, this is the first demonstration of the effects of
expertise and categorization level on activation in the FFA in a group of
typically developing children.
PMID- 23153969
TI - Evaluation and calibration of functional network modeling methods based on known
anatomical connections.
AB - Recent studies have identified large scale brain networks based on the spatio
temporal structure of spontaneous fluctuations in resting-state fMRI data. It is
expected that functional connectivity based on resting-state data is reflective
of - but not identical to - the underlying anatomical connectivity. However,
which functional connectivity analysis methods reliably predict the network
structure remains unclear. Here we tested and compared network connectivity
analysis methods by applying them to fMRI resting-state time-series obtained from
the human visual cortex. The methods evaluated here are those previously tested
against simulated data in Smith et al. (Neuroimage, 2011). To this end, we
defined regions within retinotopic visual areas V1, V2, and V3 according to their
eccentricity in the visual field, delineating central, intermediate, and
peripheral eccentricity regions of interest (ROIs). These ROIs served as nodes in
the models we study. We based our evaluation on the "ground-truth", thoroughly
studied retinotopically-organized anatomical connectivity in the monkey visual
cortex. For each evaluated method, we computed the fractional rate of detecting
connections known to exist ("c-sensitivity"), while using a threshold of the 95th
percentile of the distribution of interaction magnitudes of those connections not
expected to exist. Under optimal conditions - including session duration of
68min, a relatively small network consisting of 9 nodes and artifact-free
regression of the global effect - each of the top methods predicted the expected
connections with 67-85% c-sensitivity. Correlation methods, including Correlation
(Corr; 85%), Regularized Inverse Covariance (ICOV; 84%) and Partial Correlation
(PCorr; 81%) performed best, followed by Patel's Kappa (80%), Bayesian Network
method PC (BayesNet; 77%), General Synchronization measures (67-77%), and
Coherence (CohB; 74%). With decreased session duration, these top methods saw
decreases in c-sensitivities, achieving 59-76% for 17min sessions. With a short
resting-state fMRI scan of 8.5min, none of the methods predicted the real network
well, with Corr (65%) performing best. With increased complexity of the network
from 9 to 36 nodes, multivariate methods including PCorr and BayesNet saw a
decrease in performance. Artifact-free regression of the global effect increased
the c-sensitivity of the top-performing methods. In an overall evaluation across
all tests we performed, correlation methods (Corr, ICOV, and PCorr), Patel's
Kappa, and BayesNet method PC set themselves somewhat above all other methods. We
propose that data-based calibration based on known anatomical connections be
integrated into future network studies, in order to maximize sensitivity and
reduce false positives.
PMID- 23153971
TI - Carbapenem-resistant Klebsiella pneumoniae harbouring blaKPC-3 and blaVIM-2 from
central Italy.
AB - The frequency of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae is
increasing in Italian hospitals and poses an emerging threat to the management of
infections in hospitalized patients. In this study, we report a detailed
molecular characterization of a K. pneumoniae subsp. pneumoniae KP1/11 isolate
from the decubitus ulcer of a hospitalized patient with a serious infection. K.
pneumoniae KP1/11 produces KPC-3 and VIM-2 beta-lactamases. The bla(KPC-3) gene
is harbored in a large plasmid in a complex structure of Tn3-based transposon,
Tn4401a. The chromosomal DNA of K. pneumoniae harbored also 2 class 1 integrons
with different variable regions: 1) orfD-aacA8; 2) aacA29-bla(VIM-2).
PMID- 23153970
TI - Unbiased tensor-based morphometry: improved robustness and sample size estimates
for Alzheimer's disease clinical trials.
AB - Various neuroimaging measures are being evaluated for tracking Alzheimer's
disease (AD) progression in therapeutic trials, including measures of structural
brain change based on repeated scanning of patients with magnetic resonance
imaging (MRI). Methods to compute brain change must be robust to scan quality.
Biases may arise if any scans are thrown out, as this can lead to the true
changes being overestimated or underestimated. Here we analyzed the full MRI
dataset from the first phase of Alzheimer's Disease Neuroimaging Initiative (ADNI
1) from the first phase of Alzheimer's Disease Neuroimaging Initiative (ADNI-1)
and assessed several sources of bias that can arise when tracking brain changes
with structural brain imaging methods, as part of a pipeline for tensor-based
morphometry (TBM). In all healthy subjects who completed MRI scanning at
screening, 6, 12, and 24months, brain atrophy was essentially linear with no
detectable bias in longitudinal measures. In power analyses for clinical trials
based on these change measures, only 39AD patients and 95 mild cognitive
impairment (MCI) subjects were needed for a 24-month trial to detect a 25%
reduction in the average rate of change using a two-sided test (alpha=0.05,
power=80%). Further sample size reductions were achieved by stratifying the data
into Apolipoprotein E (ApoE) epsilon4 carriers versus non-carriers. We show how
selective data exclusion affects sample size estimates, motivating an objective
comparison of different analysis techniques based on statistical power and
robustness. TBM is an unbiased, robust, high-throughput imaging surrogate marker
for large, multi-site neuroimaging studies and clinical trials of AD and MCI.
PMID- 23153972
TI - Genetic association of adiponectin gene polymorphisms (+45T/G and +10211T/G) with
type 2 diabetes in North Indians.
AB - Adiponectin (ADIPOQ) is an abundant protein hormone which belongs to a family of
so-called adipokines. It is expressed mostly by adipocytes and is an important
regulator of lipid and glucose metabolism. It was shown that decreased serum
adiponectin concentration indicated insulin resistance and type 2 diabetes (T2DM)
with the risk of cardiovascular complications. The fact that adiponectin is an
insulin-sensitizing hormone with anti-diabetic, anti-inflammatory and anti
atherogenic properties, we proposed to study the association of ADIPOQ gene
polymorphisms in subjects with T2DM. DNA was isolated from venous blood samples,
quantified and subjected to Polymerase Chain Reaction-Restriction Fragment Length
Polymorphism (PCR-RFLP) using suitable primers and restriction endonucleases.
Adiponectin levels were measured in serum using ELISA. The genotypic, allelic and
carriage rate frequencies distribution in patients and controls were analyzed by
PSAW software (ver. 17.0). Odd ratios (OR) with 95% confidence interval (CI) were
determined to describe the strength of association by logistic regression model.
Out of the two polymorphisms studied, +10211T/G showed significant association
(P=0.042), the 'G' allele association being highly significant (P=0.022). Further
analysis showed that individuals with 'GG' haplotype were at increased risk of
T2DM up to 15.5 times [P=0.015, OR (95% CI); 15.558 (1.690-143.174)]. The present
study showed that the 'G' allele of ADIPOQ gene (+10211T/G) plays a prominent
role with respect to T2DM susceptibility in North-Indian population.
PMID- 23153974
TI - Targeting tumor necrosis factor alpha (TNF-alpha) in diabetic rats could approve
avenues for an efficient strategy for diabetic therapy.
AB - BACKGROUND: Several studies held belief that downregulation of TNF-alpha may be
effective for preventing diabetes and it's complications. However, it is not
known whether TNF-alpha downregulation in long-term can generate any biological
adverse. AIM: The aim of the present study was to clarify what the impact is for
such treatment with specific antibody for TNF-alpha on the other biological
activities after 4weeks. METHODS: Using western blot, IHC, Elisa, biochemical
assays and scanning electron microscope. RESULTS: Results show that TNF-alpha,
FOXO-1, IL-6 and MPO, when expressed in diabetic rats, collectively induce
dramatic changes in diabetic rats. Since, TNF-alpha is involved in activation of
transcription factor FOXO1 along with oxidative stress mediated by neutrophils.
On one hand, IL-6 mediates neutrophils activation leading to an augmentation in
stress mediators. And FOXO1 is activated in order to eliminate these oxidative
mediators, on the other hand. Data show also that the prominent defect in mucosal
IgA and IL-2 secretions may be the leading reasons for digestive atrophy.
Finally, Akt-1 inhibits the cleavage of caspase 3, so, it could prevent the
incidence of apoptosis. CONCLUSION: Findings of this study reveal how TNF-alpha
can be mechanistically coupled to greater diabetic complications potential.
PMID- 23153973
TI - Clinical profile of coexisting conditions in type 1 diabetes mellitus patients.
AB - AIMS: Type 1 diabetes mellitus (T1DM) is associated with various genetic and
autoimmune diseases implicated in its etiopathogenesis. We hereby profile the
clinical association of such diseases among patients from our center. METHODS:
Consecutive patients of T1DM presenting to department of Endocrinology from May
1997 to December 2011 were retrospectively analyzed in context of associated
clinical profile. RESULTS: Among 260 patients diagnosed as T1DM, 21 (8%) had
hypothyroidism, 4 (1.5%) had hyperthyroidism and 2 (0.7%) had primary adrenal
insufficiency. Eighteen patients (7%) had celiac disease, 9 (3.5%) had Turner's
syndrome, 5 patients (1.9%) had Klinefelter's syndrome, whereas Down's syndrome
and Noonan's syndrome was present in 2 and 1 patients (0.7%) respectively. One
patient had Wolframs' syndrome and 1 patients had myasthenia gravis. Systemic
lupus erythematosus and rheumatoid arthritis were present in 3 and 1 patients
respectively. Total of 5 patients with cerebral palsy, 4 cases with deaf mutism,
4 cases with acute psychosis and 16 patients with depression were noted. Mean age
of study patients was 20.8+/-9.8 years (range, 3-23 years). CONCLUSION: Various
conditions including genetic (Down, Turner, Noonan, and Klinefelter's),
autoimmune (thyroid and adrenal disorders, myasthenia gravis, SLE, rheumatoid
arthritis) and central nervous system diseases were the associated diseases
encountered in our patients. Routine screening is required for early diagnosis
and treatment of associated co morbidities.
PMID- 23153975
TI - Quantitative vibration perception threshold in assessing diabetic neuropathy: is
the cut-off value lower for Indian subjects? [Q-VADIS Study].
AB - AIMS: The aim was to compute a normative data of VPT [Vibration Perception
Threshold], compare results of VPT among type 2 diabetes patients with and
without neuropathy, validate VPT taking NDS [Neuropathy Disability Scores] as
gold standard and suggest a cut off value for the Indian population. MATERIALS
AND METHODS: A clinic based case-control study was conducted at Nightingale
Hospital (NH) in Kolkata for 2 months duration. Fifty type 2 diabetes patients
(who were detected with by fasting plasma glucose or on medication) reporting at
OPD (Out Patent Department) were randomly selected and informed consent was
obtained. The age range was 20-65 years and other common causes of neuropathy
were excluded. Same number of control patients without diabetes and reporting at
the same hospital during the study period in the similar age range were selected.
RESULTS: The normative data of VPT for mean of 4 sites (malleoli and great toe)
was 11.3+/-4.9mV. The VPT value was significantly higher among diabetic patients
with neuropathy compared to non-neuropathic and non-diabetic patients.
Considering NDS score as gold standard lowering the cutoff value of VPT from 25mV
to 20mV increased the sensitivity from 50% to 62.5% in detecting diabetic
neuropathy compared to NDS taken as a gold standard. CONCLUSIONS: It was found
that lowering the cut off value of VPT in Indian population increased the
sensitivity of the test to detect diabetic neuropathy without hampering the
specificity. There is however no indication that a lower cut off VPT value is
justified as of now.
PMID- 23153976
TI - Relationship of RIC-3 gene rs1528133 polymorphism with varying degrees of body
weight and eating behavior.
AB - AIMS: The aim of this study was to determine the allele frequencies of resistance
to inhibitors of cholinesterase 3 homologue (RIC-3) gene rs1528133 polymorphism
in overweight+obese+morbid obese and non-obese (non-OB) subjects. The effects of
rs1528133 genotypes on anthropometric, diabetes and obesity related parameters,
self-reported macronutrient intake and drugs were also evaluated. The study was
performed on overweight+obese+morbid obese and non-obese subjects. METHODS: RIC-3
gene rs1528133 genotypes were determined with qPCR. RESULTS: The RIC-3 rs1528133
genotype frequencies were respectively as 89.4% for homozygous wild type (A/A),
10.6% for heterozygous (A/C) genotypes in overweight+obese+morbid obese patients
and 92.7% for A/A, 7.3% for A/C genotypes in non-OB subjects. The homozygous
mutant genotype (C/C) was not detected in our study population. Genotype
frequencies were not significantly different among study groups. Heterozygous
genotype carriers for the rs1528133 polymorphism were found to prefer higher
glycemic load, fat and protein diet content compared to homozygous wild type
genotype carriers (p=0.0001). The frequency of rs1528133 heterozygous individuals
(16.7%) using antihypertensive drugs was lower (p=0.045) in comparison to wild
type genotype carriers (46.9%) in the whole study population. CONCLUSIONS: RIC-3
gene rs1528133 variation was not found to be effective over any analyzed obesity
related parameter, but associated with higher glycemic load, protein and fat
eating behavior and antihypertensive drug use.
PMID- 23153977
TI - Prevalence and risk factors for diabetes and impaired glucose tolerance in Asian
Indians: a community survey from urban eastern India.
AB - OBJECTIVES: To determine the prevalence of diabetes and impaired glucose
tolerance (IGT) and to identify risk factors for the same specific to an
underdeveloped urban locale of Eastern India. METHODS: Study design. Population
based cross-sectional study, with multistage random sampling technique. Setting.
Urban city-dwellers in Orissa one of the poorest states of Eastern India
bordering a prosperous state of Andhra Pradesh of Southern India. Participants.
1178 adults of 20-80 years age randomly selected from 37 electoral wards of urban
populace. Definition and diagnosis of diabetes mellitus and IGT. These were based
on a Report of a World Health Organization/International Diabetes Federation
Consultation of 2006. Main outcome measure. Prevalence and significant risk
factors for Diabetes and IGT. Statistical analysis. Both descriptive and
multivariable logistic regression analyses. RESULTS: The crude rates of diabetes
and IGT in the study population were 15.7% and 8.8%, respectively. Similarly age
standardized rates of diabetes and IGT were 11.1% and 6.7%, respectively. Both
diabetes and IGT had shown a male preponderance. CONCLUSION: Diabetes and IGT
were very highly prevalent in this urban populace. Cardiometabolic risk factors
like older age, central obesity, inadequate fruit intake, hypertension,
hypertriglyceridemia and socio economic status were found to be significant
predictors of diabetes in this study.
PMID- 23153978
TI - Influence of iron metabolism indices on HbA1c in non-diabetic pregnant women with
and without iron-deficiency anemia: effect of iron supplementation.
AB - AIMS: Condition that influence erythrocyte turnover also affect HbA1c. Although
many forms of anemia are associated with lowering of HbA1c, iron-deficiency
anemia (IDA) tends to increase HbA1c. In this study, we examined the relationship
between HbA1c and erythrocyte indices in non-diabetic pregnancy and assessed the
effect of iron supplementation on HbA1c. MATERIALS AND METHODS: 150 women were
studied (30 non-diabetic), non-pregnant, non-anemic women in child bearing women
with varying parity as controls (Gp 1); 30 non-diabetic, non-anemic pregnant
women in first trimester of pregnancy (Gp 2a); 30 non-diabetic, non-anemic
pregnant women in second trimester of pregnancy (Gp 2b); 30 non-diabetic, non
anemic pregnant women in third trimester of pregnancy (Gp 2c) and 30 non-diabetic
pregnant women with IDA (Gp 2d). HbA1c, OGTT, erythrocyte indices and iron
metabolic indices were determined in Gp 2d subjects not supplemented with iron
and repeated these indices after 3 months of iron-supplementation. RESULTS: The
mean fasting and postprandial blood glucose levels (79.9+/-8.0mg/dl, 108.1+/
14.1mg/dl) in Gp 1 were found to be significantly lower in first trimester among
Gp 2a (74.4+/-5.3mg/dl and 97.2+/-11.1mg/dl), in second trimester among Gp 2b
(76.2+/-5.2mg/dl and 103.4+/-7.9mg/dl) followed by increase in IIIrd trimester
among Gp 2c (82.3+/-5.7mg/dl and 112.5+/-8.5mg/dl) subjects. A significant
difference in HbA1c was also observed among the groups (HbA1c 4.7+/-0.3% in Gp 1;
4.6+/-0.4% in Gp 2a; 4.5+/-0.3 in Gp 2b; 4.7+/-0.3 in Gp 2c). Among Gp 2d
subjects, HbA1c was 5.2+/-0.3% and the level decreased after iron supplementation
to 5.1+/-0.3%. Significant correlation between erythrocyte indices, iron
metabolic indices and HbA1c was also observed. CONCLUSION: We conclude that
consideration should be given for performing glucose testing in patients with IDA
to ascertain the reliability of HbA1c in the diagnosis of diabetes. HbA1c
concentrations in diabetic patients with IDA should be interpreted with caution.
PMID- 23153979
TI - Endothelial nitric oxide synthase Glu298Asp (G894T) gene polymorphism in coronary
artery disease patients with type 2 diabetes mellitus.
AB - AIMS: Endothelial dysfunction is thought to be a significant risk factor for
cardiovascular disease. This study determined the role of endothelial nitric
oxide synthase (eNOS) Glu298Asp polymorphism and intergenotypic variation of
plasma nitric oxide (NO) levels in coronary artery disease (CAD) patients with
type 2 diabetes mellitus (DM). METHODS: This case-control study included 28
documented CAD patients with type 2 DM and 32 non-diabetic patients with CAD.
Fifty healthy volunteers without any major cardiovascular risk factors served as
controls. NO was estimated by modified Griess method. The eNOS gene polymorphism
was studied by amplifying DNA by PCR and digesting with BanII restriction enzyme.
Restriction fragment length polymorphism was studied by using a gel documentation
system. RESULTS: The genotype frequencies for Glu298Asp (GT) genotype were 10.71%
in diabetic CAD patients, 28.1% in non-diabetic CAD patients and 12% in controls.
The T allele frequency was higher in the non-diabetic CAD group (14%) as compared
with the diabetic CAD (5.4%) and control group (6%). NO level was significantly
lower in non-diabetic CAD patients (10.25 mmol/L) but not in diabetic CAD
patients (13.89 mmol/L) as compared to controls (16.78 mmol/L). CONCLUSION:
Glu298Asp polymorphism is not the mediator of increased incidence of CAD in
diabetic patients.
PMID- 23153980
TI - Hemoglobin A1C determination by point-of-care testing: its correlation to
standard method.
AB - The hemoglobin A1C (HbA1C) is the useful test for following up of glycemic
control of the diabetic patient. Due to the present advance in point-of-care
testing (POCT) technology, the new POCT for determination of HbA1C is available.
Here, the author performs a laboratory comparative study between the new POCT
tool (DCA) and classical tool (COBAS) for analysis of HbA1C level. This study is
the second confirmation study in Thailand performed in the new setting adding to
the previous author's report. The results show that there is a good correlation
between two techniques and the error of the POCT tool is within acceptable limit.
PMID- 23153981
TI - Oral mucositis, Steven Johnson syndrome and amlodipine usage in a case with
metabolic syndrome.
PMID- 23153982
TI - Mechanisms and techniques of reprogramming: using PDX-1 homeobox protein as a
novel treatment of insulin dependent diabetes mellitus.
AB - Homeobox proteins are key regulators of stem cell proliferation and
differentiation which function as transcription factors and regulate cell fate
decisions. Pancreatic Duodenal Homeobox-1 (PDX-1) is a homeobox protein which
acts as a key regulator in the development of b cells in the Islets of
Langerhans. It plays an important role in maintaining the identity and function
of the Islets of Langerhans, and in the development of the pancreas. There is
strong evidence that PDX-1 plays a role in activating the insulin promoter and
increasing insulin levels in response to glucose. PDX-1 also binds to sequences
within beta cells and regulates the promoter activity of a number of islet genes
including insulin, glut-2 and neurogenin 3. When fused with the VP16 activation
sequence, transfection of the PDX-1 gene has been shown to transform liver cells
into insulin producing cells. Because homeobox proteins are able to passively
translocate through cell membranes, due to an intrinsic transduction domain
(penetratin), the use of these proteins to reprogram target cells may help
overcome the limiting supply of beta cells and be a potential future treatment
for Type 1 diabetes.
PMID- 23153983
TI - Visfatin and its role in obesity development.
AB - Visfatin, a product of PBEF gene, is an adipocytokine that harbours strong
insulin-mimetic activity and it has been reported previously to associate with
obesity. Recent reports also provide evidence that Visfatin has also important
intracellular effects as it is homologous with nicotinamide
phosphoribosyltransferase (NAMPT). In this review, we summarize the main
documented effects of Visfatin on metabolism in humans, with special emphasis put
on the pathways associated with obesity.
PMID- 23153984
TI - Prospective monitoring N-terminal pro-brain natriuretic peptide during natural
progression of atherosclerotic renal artery stenosis in elderly.
AB - Prognostic values of N-terminal pro-brain natriuretic peptide (NT-proBNP) in
myriad diseases have been studied. During the natural progression of
atherosclerotic renal artery disease (ARVD) changes of NT-proBNP levels and its
significance is not understood. A prospective longitudinal follow-up study was
conducted among 61 ARVD patients (77.7 +/- 5.2 years old). NT-proBNP was
determined at baseline and six month intervals over 25.89 +/- 12.44 months and
its correlation with death and/or newly occurred CVEs were assessed. Level of NT
proBNP increased from baseline median 210.0 pg/mL (25th-75th percentile, 98.0
pg/mL-540.0 pg/mL) to 900.9 pg/mL (25th-75th percentile, 704.5 pg/mL-1583.5
pg/mL) (p=0.032) at the end of follow-up. Among 44.26% of the cohort (n=27) NT
proBNP level >=450 pg/mL was detected, which 6 deaths happened (22.22% death
rate) and CVEs occurred to 62.96% of patients, comparing to 0% death rate
(p=0.077) and 8.82% affected by CVEs (p=0.019) in other 55.74% of cohort (n=34)
whose NT-proBNP <450 pg/mL. Kaplan-Meier analysis showed that NT-proBNP level
>=450 pg/mL was a risk factor related to CVEs (HR=3.96, p=0.03). Cox regression
analysis found NT-proBNP level >=450 pg/mL was an independent risk factor of CVEs
(HR=5.12, p=0.022) after adjustment of body mass index, blood pressure, kidney
function. The negative predictive value was 90.9% of NT-proBNP levels >=450 pg/mL
for new CVEs. NT-proBNP levels diverge throughout ARVD natural progression in
elderly males over 75 years of age. Elevated NT-proBNP level of >=450 pg/mL was
predictive for CVEs with 90.9% of negative predictive value.
PMID- 23153985
TI - Gender differences in factors influencing sexual satisfaction in Korean older
adults.
AB - This study investigates the sex lives of Korean older adults (i.e., those over 60
years) and attempts to identify gender-related factors influencing sexual
satisfaction. It used data from the 2008 Korean National Survey on Older Adults
conducted by the Ministry of Health, Welfare, and Families. Of the 15,146
individuals who had taken part in the 2008 study, secondary analysis was
conducted with data from 3360 persons who had spouses and were willing to respond
to sex-related questions in a face-to-face interview. The mean age of male and
female subjects was 67.34 and 66.86 years respectively. In the male subjects,
sexual frequency, followed by marital satisfaction and cognitive function, had
the greatest effect on sexual satisfaction. These three variables together
accounted for 21% of the male subjects' sexual satisfaction. In the female
subjects, marital satisfaction, followed by frequency of sexual activity, absence
of depressive symptoms, age, and length of cohabitation with spouse, had the
greatest effect on sexual satisfaction. These five variables together explained
11% of their sexual satisfaction. This study indicates that sexual frequency and
physical factors have the most important effects on the sex lives of older men,
while older women value psychosocial and relational factors more highly.
Therefore, interventions aiming to improve sexual satisfaction in older adults
should take gender differences into account.
PMID- 23153986
TI - [18F-FDG PET/CT diagnosis of liver cyst infection in a patient with autosomal
dominant polycystic kidney disease and fever of unknown origin].
AB - The diagnosis, localization and treatment of infected cysts in the kidney or
liver of patients with autosomal dominant polycystic kidney disease (ADPKD)
remain a clinical challenge. We report the findings of (18)F-FDG PET-CT in an
ADPKD diagnosed patient who required renal transplantation five years before and
in his follow up presented repeated episodes of bacteriemia without known focus
on radiological tests performed. The (18)F-FDG PET-CT scan showed numerous
hypermetabolic images with focal or ring-shaped morphology related to the content
and the wall of some hepatic cysts. The increased metabolic activity was
localized on segments VI and VII. We proceeded to drainage of one cyst in segment
VI, removing 110 cc of purulent fluid which grew E. Coli BLEE. The (18)F-FDG
PET/CT scan should be included in the diagnostic algorithm for detecting infected
liver cysts in patients with ADPKD and fever of unknown origin.
PMID- 23153987
TI - Application of 99mTc-denatured red blood cells scintigraphy in the evaluation of
post-traumatic spleen auto-transplantation.
PMID- 23153988
TI - Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT)
for the detection of skeletal muscle and skin metastases in uterine
leiomyosarcoma: a case report.
AB - We report the clinical value of FDG PET/CT imaging in a 57-year-old woman who was
diagnosed with uterine leimyosarcoma 6 years ago. In a staging procedure, whole
body FDG PET/CT discloses the presence of both local recurrence and remote
metastases at widespread musculocutaneous sites, liver and femur. With its
advantage of scanning the whole body in a single procedure, we propose the use of
PET/CT imaging for the evaluation of patients with uterine leimyosarcomas, a
tumor with a propensity for widespread hematogenous spread to unusual sites.
PMID- 23153989
TI - Gestational diastolic hypertension with gene mutation-related pheochromocytoma
positive at 18F-DOPA PET/CT: diagnostic and therapeutic implications.
PMID- 23153990
TI - PPARgamma regulates the mitochondrial dysfunction in human neural stem cells with
tumor necrosis factor alpha.
AB - Peroxisome proliferator-activated receptor gamma (PPARgamma) belongs to a family
of ligand-activated transcription factors, and its ligands are known to control
many physiological and pathological conditions. The hypothesis of our study was
that the PPARgamma agonist (rosiglitazone) could mediate tumor necrosis factor
alpha (TNFalpha) related to the regulation of human neural stem cells (hNSCs), by
which TNFalpha possibly fulfills important roles in neuronal impairment. The
results show that PPARgamma mediates the cell viability of hNSCs via the
downregulation of the activity of caspase 3, indicating that this rescue effect
of PPARgamma could improve the reduced levels of two mitochondrial regulators,
adenosine monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1) in
the hNSCs with TNFalpha. The stimulation of mitochondrial function by PPARgamma
was associated with activation of the PPAR coactivator1 alpha (PGC1alpha) pathway
by up-regulation of oxidative defense and mitochondrial systems. The above
protective effects appeared to be exerted by a direct activation of the
rosiglitazone, because it protected hNSCs from TNFalpha-evoked oxidative stress
and mitochondrial deficiency. Here we show that the rosiglitazone protects hNSCs
against Abeta-induced apoptosis and promotes cell survival. These findings extend
our understanding of the central role of PPARgamma in TNFalpha-related neuronal
impairment, which probably increases risks of neurodegenerative diseases. The
anti-inflammatory effects of PPARgamma in the hNSCs with TNFalpha, and the
involved mechanisms were also characterized.
PMID- 23153991
TI - Differential regulation of CDK5 and c-Fos expression by morphine in the brain of
Lewis and Fischer 344 rat strains.
AB - The aim of this study was to comparatively study cyclin-dependent kinase 5 (CDK5)
and c-Fos regulation by morphine in the brains of Lewis and Fischer 344 (F344)
rats, which are known to differ in their behavioral sensitivities to several
drugs of abuse. Two hours after an acute i.p. administration of morphine (10 mg
kg(-1)) or saline (control), the animals were perfused and their brains prepared
for immunohistochemistry. The number of CDK5 immunoreactive cells was
significantly higher in the nucleus accumbens (NAC), the locus coeruleus (LC) and
the nucleus tractus solitarius (NTS) of saline-injected F344 rats than in those
of the Lewis rats. Morphine upregulated CDK5 with a varying pattern depending on
the strain and brain area. The effect of the opioid was more marked in the NTS of
the Lewis rats and the NAC of the F344 rats. Immunostaining of c-Fos was very low
or absent in the control animals and was consistently up-regulated by morphine,
especially in the LC and NTS of the F344 rats and the NAC of the Lewis rats. We
propose that the acute morphine regulation of CDK5 expression in the NAC may
predict the rate of drug intake and/or extinction of drug seeking, while the
pattern of c-Fos activation may be more related to the differential acquisition
of morphine-seeking behaviors.
PMID- 23153992
TI - History of the New York Roentgen Society.
PMID- 23153994
TI - Three-dimensional MRI with contrast diagnosis of diseases involving peripheral
oculomotor nerve.
AB - PURPOSE: The purpose was to evaluate three-dimensional magnetic resonance imaging
with contrast (3D-CEMRI) in displaying peripheral oculomotor nerve (PON) and
diagnosing peripheral oculomotor nerve diseases (POND). MATERIALS AND METHODS:
The MRI findings of 80 patients with POND were reviewed and compared with digital
subtraction angiography (DSA), operative or pathological results, and final
clinical diagnosis. RESULTS: Twenty-three aneurysms (23/26) confirmed by DSA were
detected with Magnetic Resonance Angiography (MRA). Twenty-five inflammatory
lesions, 14 malignant lesions, and 5 benign lesions involving PON were shown with
3D-CEMRI corresponding with clinical diagnosis and pathology. Another 13 (13/80,
16.03%) cases were negative on MRI. CONCLUSION: 3D-CEMRI with MRA could show and
diagnose the majority of the diseases involving PON.
PMID- 23153993
TI - Spectrum of malignant renal and urinary bladder tumors on 18F-FDG PET/CT: a
pictorial essay.
AB - A wide variety of malignant renal and urinary bladder diseases can be detected on
(18)F-FDG PET/CT. Although the PET/CT findings are often nonspecific, the aim of
this atlas was to demonstrate that the spectrum of renal and urinary bladder
malignancy that can be evaluated with PET/CT is much broader than current medical
literature would suggest. PET/CT readers and oncologists should be aware of the
variety of urological tumor types that can be detected on PET/CT and some of the
patterns of (18)F-FDG uptake that can be observed in these cases.
PMID- 23153995
TI - Role of perfusion CT in differentiating between various cerebral masses using
normalized permeability surface area product and cerebral blood volume.
AB - OBJECTIVE: The objective was to assess usefulness of a combined analysis using
the perfusion computed tomography parameters permeability surface area product
(PS) and cerebral blood volume (CBV) in the differential grouping of various
cerebral masses. METHODS: Thirty patients who had a cerebral mass, confirmed by
pathologic verification, were included. We classified PS and CBV results for
various cerebral masses by visual as well as semiquantitative assessment. To
verify statistically significant differences between the groups, one-way analysis
of variance was performed. RESULTS: Patients were categorized into five groups
with statistically significant differences (P<.01). CONCLUSIONS: PS and CBV were
useful in the differential diagnosis of cerebral masses.
PMID- 23153996
TI - Parathyroid adenoma screening efficacies of different imaging tools and factors
affecting the success rates.
AB - PURPOSE: We aimed to compare the efficacy of three different parathyroid adenoma
screening tools--high-resolution ultrasonography (USG), technetium Tc 99m
methoxyisobutylisonitrile (MIBI) parathyroid scintigraphy, and magnetic resonance
imaging (MRI)--and we evaluated the factors affecting the detection success
rates. METHODS: Parathyroid imaging was evaluated by USG, double-phase 99mTc-MIBI
parathyroid scintigraphy, and cervical MRI in patients with hyperparathyroidism
(n=39). RESULTS: Among the 39 patients, USG, parathyroid scintigraphy, and MRI
correctly identified 35 adenomas (89.7%), 28 adenomas (71.8%), and 26 adenomas
(66.7%), respectively. Positive predictive values for USG (34/35), scintigraphy
(27/28), and cervical MR (26/26) imaging were 97.1%, 96%, and 100%, respectively.
Parathyroid adenomas were detected with 92.3% (36/39) certainty when both USG and
scintigraphy modalities were applied together. Minimally invasive
parathyroidectomy under local anesthesia with unilateral incision was
successfully performed in 24 (61.5%) patients. CONCLUSIONS: Minimally invasive
surgery for parathyroid adenomas has been developed and has equal success with
traditional surgery. However, accurate localization of adenomas should be
obtained prior to surgery. In this study, ultrasound was found to be effective in
localizing adenomas for successful surgery. Adding other imaging modalities does
not improve localizing the parathyroid adenomas.
PMID- 23153997
TI - Functional magnetic resonance imaging of methamphetamine craving.
AB - The study aimed to explore the abnormal activation of special brain areas
associated with methamphetamine craving using functional magnetic resonance
imaging (fMRI) and to reveal the neurobiological basis of addiction. Twenty-six
methamphetamine addicts and 26 healthy subjects were scanned by brain fMRI while
watching pictures of happy, sad, or methamphetamine to acquire resource data.
SPM5 was used to analyze fMRI data to get related brain activation map, and it
was found that methamphetamine addicts had high brain activation in cingulate and
low activation in frontal lobe when watching methamphetamine-cue pictures. This
study demonstrated that methamphetamine addicts had emotion-related brain
activation abnormalities.
PMID- 23153998
TI - MRI and 1H-MRS on diagnosis of pineal region tumors.
AB - PURPOSE: The purpose was to analyze characteristic magnetic resonance (MR)
imaging of pineal region tumors and to explore the value of diffusion-weighted
imaging (DWI) and (1)H-MR spectroscopy ((1)H-MRS) in differential diagnosis among
four common solid diseases: germinoma, teratoma, pineoblastoma, and glioma.
METHODS: Thirty-three patients with pineal region tumors proven by pathology were
prospectively studied. All of them underwent MRI SE-T1WI, FSE-T2WI, fluid
attenuated inversion recovery (FLAIR), and postcontrasted MR scan. Minimum
apparent diffusion coefficient (ADC) value, and maximum MRS choline/N-acetyl
aspartate (Cho/NAA) and lipid/creatine (Lip/Cr) metabolic peak-height ratios were
quantified within each lesion. RESULTS: Most pineal region diseases have their
typical morphology, signal intensity, and enhancement style. ADC values were
lower in germinoma [(6.98+/-0.35)*10(-4)] and pineoblastoma [(9.14+/-0.79)*10(
4)] than in teratoma [(2.80+/-0.18)*10(-3)] and pineal glioma [(1.63+/-0.66)*10(
3)] (P<.05). Cho/NAA ratios were higher in germinoma (2.09+/-0.39), pineoblastoma
(4.70+/-0.82), and pineal glioma (3.54+/-0.38) than in teratoma (1.52+/-0.91)
(P<.05). Lip/Cr ratios were lower in germinoma (2.52+/-0.41) than in teratoma
(8.47+/-1.16) (P<.05). CONCLUSIONS: Changes in morphologic features, signal
intensity, and enhancement style are the most helpful variables for the
differential diagnosis of pineal region tumors. To some extent, DWI and (1)H-MRS
imaging enable distinction among them.
PMID- 23153999
TI - Mammogram-based discriminant fusion analysis for breast cancer diagnosis.
AB - Mammogram-based classification is an important and effective way for computer
aided diagnosis (CAD)-based breast cancer diagnosis. In this paper, we present a
novel discriminant fusing analysis (DFA)-based mammogram classification CAD-based
breast cancer diagnosis. The discriminative breast tissue features are exacted
and fused by DFA, and DFA achieves the optimal fusion coefficients. The largest
class discriminant in the fused feature space is achieved by DFA for
classification. Beside the detailed theory derivation, many experimental
evaluations are implemented on Mammography Image Analysis Society mammogram
database for breast cancer diagnosis.
PMID- 23154000
TI - Combination of high-intensity focused ultrasound with nanoscale ultrasound
contrast agent in treatment of rabbit breast VX2 tumors: a pilot study.
AB - To demonstrate ultrasound contrast agents to be important potentiators of high
intensity focused ultrasound (HIFU), we prospectively assessed the effectiveness
of HIFU combined with nanoscale ultrasound contrast agents for the treatment of
breast VX2 tumors in rabbits. We found that the change of grayscale value in the
target area in the HIFU+nanobubble group was significantly higher than that in
the HIFU+phosphate-buffered saline (PBS) group after irradiation (P<.01). The
size of coagulation necrosis was also significantly larger in the HIFU+nanobubble
group when compared to that in the HIFU+PBS group (P<.001). In conclusion, our
study suggested that adding nanoscale ultrasound contrast agents may improve the
treatment efficacy of HIFU for breast VX2 tumors in rabbits.
PMID- 23154001
TI - Computed tomography coronary angiography and invasive coronary angiography
demonstrate high correlation for area stenosis quantification in noncalcified and
mixed plaques.
AB - We compared the variance of area and diameter significant stenosis measurement
between quantitative computed tomography coronary angiography (QCTA) and
quantitative invasive coronary angiography (QCA). Fifty patients presenting 65
significant coronary artery stenoses (>=70% area stenosis) in QCTA and QCA were
included. Spearman's rank correlation revealed that area stenosis measurement by
QCTA and QCA yields higher correlation than diameter stenosis and is highest for
noncalcified and mixed lesions.
PMID- 23154002
TI - Follow-up examination of 12 heart transplant recipients with cardiac CT.
AB - OBJECTIVE: The aims of this study were to observe the changes of a transplanted
heart with cardiac computed tomography (CT) and to evaluate the clinical
application of the examination. METHODS: Cardiac CT was performed on 12 heart
transplant recipients, of which 4 cases were also examined by echocardiography.
Coronary arteries, the cardiac chamber, and the wall were shown with three
dimensional imaging techniques, and their changes were analyzed and discussed.
RESULTS: Twelve heart transplant recipients were successfully examined by CT. All
transplanted hearts were found with good anastomosis at the great vessels and
atria. Coronary allograft vasculopathy was found in 7 cases, of which 4 cases
were found with ventricular dilation or ventricular septum thickening and 1 with
tricuspid regurgitation. Ventricular dilation was found in other 3 cases, of
which 1 was found with ventricular septum thickening and 1 with tricuspid
regurgitation. No abnormality was found by cardiac CT in the rest 2 cases, which
were found with mitral regurgitation by echocardiography. CONCLUSION: Cardiac CT
can clearly and directly display the changes in the shape of a transplanted heart
and coronary artery abnormalities. It will become an ideal noninvasive follow-up
method for the heart transplant recipients.
PMID- 23154003
TI - Primary lung cancers <1 cm found with MR screening appeared larger with half
Fourier sequences than with three-dimensional acquisition techniques.
AB - PURPOSE: The purpose was to objectively evaluate image quality characteristics of
half-Fourier single-shot turbo spin-echo (HASTE) and three-dimensional volumetric
interpolated breath-hold examination (3D-VIBE) for small (<1 cm) lung cancers
found by magnetic resonance imaging (MRI) screening. METHODS: From 2000 to 2009,
19,000 normal subjects were screened by MRI, and 15 cases were found to have lung
cancers <1 cm. Those nodules were analyzed by image quality indices such as the
signal to noise ratio, signal difference to noise ratio, percent contrast,
percent contrast to noise ratio, and signal ratio of tumor to normal lung
parenchyma. The area of the tumors measured by the two MR sequences and the
computed tomography (CT) was compared. RESULTS: The lung cancers showed
significantly higher percent contrast, percent contrast to noise, and the signal
ratio of tumor to normal lung parenchyma by 3D-VIBE as compared to HASTE. Tumor
area estimated by HASTE was significantly larger than that estimated by VIBE.
There was no significant difference in the signal to noise ratio and signal
difference to noise ratio between the two MR sequences. CONCLUSIONS: The 3D
acquisition technique offers high contrast and contrast to noise ratios, while
HASTE is associated with closer approximation of area estimation as compared to
CT. Both sequences have similar signal to noise ratios and signal difference to
noise ratios. The HASTE sequence is considered to be an essential part of imaging
protocol in MR screening of lung especially for small nodules.
PMID- 23154004
TI - Cardiovascular computed tomography angiography in newborns and infants with
suspected congenital heart disease: retrospective evaluation of low-dose scan
protocols.
AB - Twelve infants (body weight, 3.59+/-1.36 kg) with congenital heart disease
underwent a clinically indicated cardiovascular computed tomography angiography
(CTA) study. Retrospectively, we investigated the feasibility and diagnostic
capability of different non-electrocardiogram-triggered CTA protocols and
assessed radiation doses. Scans were performed on a 256-multislice CT (MSCT)
scanner with the vendor-preset helical protocol at 120 kV for babies, with axial
single-shoot scans at 120 kV and 80 kV. The 80-kV protocol led to significantly
reduced mean effective doses of 0.29+/-0.08 mSv (P=.017) and renders diagnostic
image quality. All major cardiovascular defects were detected on MSCT, and all
images were of diagnostic quality.
PMID- 23154005
TI - Effectiveness of a breath-hold monitoring system in improving the reproducibility
of different breath-hold positions in multiphasic CT imaging.
AB - This study tests whether the utilization of an electronic breath-hold monitoring
device improves breath-hold reproducibility during computed tomographic (CT)
scanning. Two cohorts of 40 patients underwent dual-phase abdominal CT scans,
either with a breath-hold monitoring device or with the standard breath-holding
technique. Two blinded readers measured the differences in diaphragmatic position
between phases. There was no statistical difference in diaphragmatic position
(P=.14) between the monitored (8.5+/-11.5 mm) and control (5.6+/-5.2 mm) cohorts.
Ten percent of patients from the monitored cohort had greater than 20 mm of
deviation, versus 0%-2.5% for the control cohort. Reproduction of breath-holding
position remains challenging, even with a monitoring system.
PMID- 23154006
TI - Evaluation of normal appendix vermiformis in adults with multidetector computed
tomography.
AB - To determine the utility of different contrast enhancement phases (unenhanced,
arterial, and venous), slice thicknesses (0.5, 3, and 5 mm), and planes (axial
and coronal) in the evaluation of appendix vermiformis (AV) on multidetector
computed tomography (MDCT), CT examinations of 600 patients were obtained. No
significant difference was found between the different imaging planes, slice
thicknesses, and contrast enhancement phases in terms of detection rates of AV.
The mean diameter of AV in the axial plane (5.93+/-0.06 mm) was significantly
lower than that in the coronal plane (6.18+/-0.06 mm). Evaluation of AV on MDCT
is enhanced by combined interpretation on axial and coronal planes.
PMID- 23154007
TI - Imaging late complications of cholecystectomy.
AB - OBJECTIVE: To review the imaging findings in late complications of
cholecystectomy. CONCLUSIONS: Late postcholecystectomy complications include
papillary stenosis, choledocholithiasis, biliary stricture, remnant gallbladder,
and dropped gallstones. Such complications can cause substantial morbidity, and
knowledge of the imaging appearances can facilitate expeditious diagnosis and
treatment.
PMID- 23154008
TI - The relationship between ureteral stone characteristics and secondary signs in
renal colic.
AB - PURPOSE: To assess correlations between stone size/location and severity of
secondary signs for ureteral obstruction. METHODS: Unenhanced multi-detector
computed tomography examinations of 150 patients with acute renal colic were
reviewed. Stone size, location in the ureter, kidney size and Hounsfield unit
values, perinephric edema, and degree of hydronephrosis were assessed. RESULTS:
Pale kidney sign was detected in 36%. Hydronephrosis was mild in 63% and severe
in 21%; severe hydronephrosis was associated with larger stones. Mid-ureter and
ureteropelvic junction stones were more likely to cause hydronephrosis.
Perinephric edema (56%) was not correlated with stone size/location. CONCLUSION:
Only severe hydronephrosis was significantly associated with larger stone size.
PMID- 23154010
TI - Cancer in pregnancy: cross-sectional oncologic imaging utilization at a tertiary
care center with an algorithmic approach to imaging.
AB - PURPOSE: To review utilization of imaging in pregnant patients with malignancies
and define an imaging algorithm in this patient population. METHODS: Pregnant
patients with concurrent diagnoses of malignancy from January 2002 to January
2011 were identified using an institutional electronic medical record system.
Patients with history of malignancy concurrent with pregnancy who had documented
cross-sectional imaging studies were included. Clinical charts were reviewed, and
patient demographics, diagnoses, indication for imaging, imaging findings, and
oncologic stage were recorded. Descriptive statistics were performed. RESULTS:
Thirty-eight women were identified with malignancy concurrent with pregnancy.
Twenty-seven patients had cross-sectional imaging studies during their pregnancy.
There were 20 new diagnoses of malignancy and 7 with recurrent tumor. The most
common new malignancies were lymphoma (5/27, 19%) and breast cancer (4/27, 15%).
Two thirds (18/27, 66%) of the patients underwent at least one imaging study
associated with ionizing radiation. CT imaging was utilized in 13 (48%) of 27
patients and MRI was used in 14 (52%) of 27 patients. Fifteen (75%) of the 20
patients with new diagnoses underwent oncologic staging with imaging that meets
the standard of care based on National Comprehensive Cancer Network guidelines.
An imaging algorithm was created as a guideline for the most common malignancies
in pregnancy. CONCLUSIONS: Cross-sectional oncologic imaging in the pregnant
patient involves a variety of imaging modalities including those with ionizing
radiation. This imaging largely follows standard of care for the nonpregnant
patient and is tailored to specific patient complaints. A generalized algorithm
is offered here for imaging pregnant oncology patients.
PMID- 23154009
TI - A comparison of pyelography and various reconstructions of multidetector helical
computed tomography urography images for diagnosing urinary obstruction.
AB - Radiologists and urologists require practical and helpful image reconstructions
for diagnosing urinary obstruction. We performed different types of imaging and
reconstruction, then used a self-designed urinary obstruction-specific
questionnaire to evaluate the diagnostic outcome of them. Our results suggested
that two-dimensional (2D) axial computed tomography (CT) is clinically superior
to retrograde pyelography or antegrade pyelography, and to other modes of image
reconstruction that are often used for diagnosing urinary obstruction.
PMID- 23154011
TI - Rotator cuff tears: association with acromion angulation on MRI.
AB - OBJECTIVE: Using magnetic resonance imaging (MRI), evaluate the correlation of
acromion angulation with thickening of the coracoacromial ligament (CAL) and
narrowing of the subacromial space resulting in impingement upon the rotator cuff
tendons. MATERIALS AND METHODS: Eighty-nine shoulder MRI studies performed on a
3T scanner were retrospectively analyzed by two blinded independent reviewers.
Measurements of the acromion angle (delta angle), CAL thickness and distance
between the CAL and humeral head were obtained. The data were categorized into
two groups, delta angle less that and greater than 7.5 degrees . The presence or
absence of full thickness (FT) or near full thickness (NFT) rotator cuff tears
was noted. RESULTS: In group 1, the acromion angle varied from -6.8 to 6.8
degrees (1.7+/-3.5 degrees ) with a CAL thickness of 0.91+/-0.20 mm and a
subacromial distance of 6.47+/-0.88 mm. Group 2 acromion angle varied from 7.6
degrees to 46.8 degrees (18.0 degrees +/-8.1 degrees ) with a CAL of 1.77+/
0.51 mm and a subacromial distance of 4.52+/-0.82 mm. The difference in CAL
thickness and subacromial distance were significantly different between the two
groups (P<.001). In Group 1, 3 out of 51 patients had a FT or NFT tear of the
rotator cuff compared to 20 out of 38 in Group 2 (P<.001). There was no
significant interobserver variability. CONCLUSION: Steep acromion angulation is
associated with CAL thickening and narrowing of the subacromial space. Patients
with a steep acromion angle had a statistically increased incidence of rotator
cuff tears.
PMID- 23154012
TI - Imaging features of posterior limbus vertebrae.
AB - Posterior limbus vertebra (PLV) is the retropulsion of the vertebral ring
apophysis resulting from disc herniation through posterior ring physis. Large PLV
can cause spinal stenosis, and small PLV can be mistaken as intraspinal disc
herniation. Although the clinical presentations were similar, the surgery was
quite different. We had experienced preoperative misdiagnosed cases and the
surgery could not be finished. Therefore we analyzed the imaging features of PLV
in 34 patients in order to prompt appropriate preoperative diagnosis and surgical
planning.
PMID- 23154013
TI - Complementary effect of H MRS in diagnosis of suprasellar tumors.
AB - OBJECTIVE: Suprasellar tumors are considered exceptionally important in
neurosurgical practice due to their proximity to vital portions of the brain.
Predicting histology of these tumors is of prime importance in determining the
surgical approach, prognosis, and probable postoperative complications. There are
numerous cases where computed tomography and magnetic resonance imaging (MRI)
fail to predict histology. We have studied the role of magnetic resonance
spectroscopy (MRS) in the diagnosis of suprasellar tumors. METHODS: Twenty-three
patients with primary nonfunctional suprasellar tumors and high-quality magnetic
resonance spectra were studied. The most probable diagnosis (adenoma, meningioma,
craniopharyngioma, or astrocytoma) was made by a neuroradiologist based on the
MRI findings and then based on MRI plus MRS findings. Finally, the results were
compared with the pathology report. RESULTS: The information provided by MRS led
the radiologist to alter his prior diagnosis that was based on the MRI in four
patients, and the final diagnoses were in accordance with the histopathology.
Wrong diagnosis was made by MRI plus MRS in three patients. Test efficiency of
MRI was 69.6%, and it was 87% for MRI plus MRS. However, the difference was not
statistically significant (P value=.152). CONCLUSION: MRS may be useful in
providing a more improved preoperative diagnosis of suprasellar tumors.
PMID- 23154014
TI - Fatigue-induced changes in longitudinal relaxation time determined by magnetic
resonance imaging.
AB - Longitudinal relaxation time (T(1)) determined by 3.0-T magnetic resonance
imaging of the tibialis anterior and extensor digitorum longus muscles increased
gradually with muscle fatigue caused by three 120-s periods of repeated ankle
dorsiflexion separated by 5-min rest periods. T(1) values decreased in the
recovery period, although they remained higher than the preexercise values. T(1)
values for the soleus muscle were unchanged throughout the experiment. Results
suggest that muscle T(1) values increase with increasing muscle fatigue.
PMID- 23154015
TI - Aberrant right common carotid and subclavian arteries causing tracheoesophageal
compression combined with persistent left superior vena cava--case report.
AB - Vascular rings are a rare group of congenital thoracic vascular anomalies which
are characterized by abnormal vascular structures that completely or incompletely
encircle the trachea, esophagus, or both. We report the case of a vascular ring
formed around the trachea and esophagus by aberrant right subclavian artery and
aberrant right common carotid artery, associated with persistent left superior
vena cava, complete absence of azygos vein, and with multiple nonvascular
abnormalities. Recurrent pulmonary infections were the only clinical
manifestation of this complex vascular anomaly. Our report represents a so-far
undescribed anatomic variation of the vascular ring that clinicians should be
aware of.
PMID- 23154016
TI - Relapsing suppurative neck abscess after chemocauterization of pyriform sinus
fistula.
AB - We report a case of relapsing suppurative neck abscess due to a pyriform sinus
fistula ever treated by chemocauterization. Pyriform sinus fistula is rare, and
chemocauterization is an alternative microinvasive procedure. This case indicates
that the possibility of recurrence following management of chemocauterization
exists even after a long time and that clinical radiological assessments are
necessary.
PMID- 23154017
TI - Diabetic mastopathy: a case report.
AB - Diabetic mastopathy (DMP) is an uncommon collection of clinical, radiological,
and histological features, classically described in premenopausal women with long
term insulin-dependent diabetes mellitus. This entity can mimic breast carcinoma,
but, in the appropriate clinical and imaging setting, the diagnosis can be made
by core biopsy, avoiding unnecessary surgeries. We report the case of a 34-year
old female, with a 12-year history of type 1 diabetes, who presented with
bilateral breast lumps. Mammography, ultrasonography, and magnetic resonance
imaging could not exclude the suspicion of malignancy, and a core biopsy was
performed showing the typical histologic features of DMP. The literature is
briefly reviewed.
PMID- 23154018
TI - Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH)
masquerading as metastatic carcinoma with multiple pulmonary deposits.
AB - Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare
pulmonary disorder presenting with multiple pulmonary nodules in association with
a typical mosaic perfusion pattern on computed tomography. In this case, the
absence of mosaic perfusion led to an erroneous initial diagnosis of pulmonary
metastases from an unknown primary malignancy. This illustrates the importance of
considering differential diagnoses when presented with imaging findings
compatible with pulmonary metastases from an unknown primary, and highlights the
importance of histopathologic confirmation in such cases.
PMID- 23154019
TI - Thymic cyst arising in the middle mediastinum posterior to the left atrium--a
peculiar location.
AB - While masses of thymic origin are commonly located within the anterior
mediastinum, abnormal migration of thymic tissue during development can result in
thymic lesions in other intrathoracic locations. Ectopic thymic lesions in the
middle mediastinum are extremely rare. We present a case of a calcified thymic
cyst located posterior to the left atrium entirely within the caudal aspect of
the middle mediastinum, a location not previously reported.
PMID- 23154020
TI - Ventricular tachycardia in a patient with double valve replacement and bilateral
coronary artery fistulas.
AB - A young patient presented with hemodynamic instability due to wide QRS
tachycardia occurring about 10 years after double valve replacement. Bilateral
coronary artery fistulas draining into the pulmonary artery were documented by
invasive coronary angiography as well as by computed tomography imaging. A
calcified scar of the posterolateral left ventricle was considered to be the
origin of the clinical ventricular tachycardia. Although additional pathological
findings are rare in young patients with valvular heart disease, diagnostic
imaging of the heart is mandatory prior to cardiac surgery.
PMID- 23154021
TI - Isolated unilateral absence of pulmonary artery mimicking chronic pulmonary
embolism at chest X-ray: multidetector-row CT angiographic findings.
AB - Unilateral absence of pulmonary artery (UAPA) is a rare congenital anomaly which
can seldom be isolated (1:200,000) and incidentally discovered in adulthood. We
describe the case of a 54-year-old male patient who was found to have isolated
UAPA (IUAPA) during the clinical and radiological investigation of a single
episode of hemoptysis. Although abnormal, chest X-ray findings differed
considerably from those previously reported and the diagnosis was only achieved
by multidetector-row computed tomography angiography and later confirmed by bed
side echocardiography. Further clinical and instrumental investigation revealed
systemic hypertension (158/95 mmHg) and bilateral mild hydronephrosis which both
remitted after transurethral prostatic adenomyomectomy.
PMID- 23154022
TI - Popliteal artery entrapment syndrome with thrombosed popliteal aneurysm:
multidetector computed tomography angiography findings of a case.
AB - Popliteal artery entrapment syndrome (PAES) is a rare congenital vascular
pathology caused by the compression of the popliteal artery by adjacent muscle
and tendinous structures. Popliteal artery aneurysm associated with this syndrome
is extremely rare. A 45-year-old male suffering from pain at the right lower
extremity during exercise was admitted to our hospital. Physical examination and
Doppler imaging revealed a weak pulse at the posterior tibial artery and no pulse
at dorsalis pedis and anterior tibial arteries. The patient was further evaluated
with multidetector computed tomography angiography (MDCTA). MDCTA revealed PAES
due to compression of the accessory fibers of the gastrocnemius muscle and
related thrombosed popliteal aneurysm.
PMID- 23154023
TI - Invasive thymoma with venous intraluminal extension: CT and MRI findings.
AB - We herein report an unusual case of invasive thymoma with venous intraluminal
extension. The thymoma extended into the superior vena cava, the left
brachiocephalic vein, and the proximal portion of the left jugular and subclavian
veins intraluminally. It was suggested that the tumor had a discrete
intravascular growth via the thymic vein into the left brachiocephalic vein and
extended into the proximal portion of the left jugular and subclavian veins in
the opposite direction of the venous stream.
PMID- 23154024
TI - Xanthogranulomatous prostatitis: a rare entity resembling prostate adenocarcinoma
with magnetic resonance image picture.
AB - Granulomatous prostatitis, characterized by chronic granulomatous inflammation in
the prostate, is rare. Xanthogranulomatous prostatitis is an even rarer
granulomatous inflammation. We present a 74-year-old man who presented with lower
urinary tract symptoms and elevated prostate specific antigen. A transrectal
ultrasonography-guided prostate biopsy was performed, and pathological results
showed foamy macrophage and inflammatory cell infiltrates, which were a
distinctive feature of xanthogranulomatous prostatitis. We also present the
characteristics of magnetic resonance imaging in xanthogranulomatous prostatitis
which has never been previously described.
PMID- 23154025
TI - Acute ischemic cholecystitis after transarterial chemoembolization with drug
eluting beads.
AB - Transarterial chemoembolization (TACE) is a widely used treatment choice for
hepatocellular cancer. DC Bead microspheres are a new embolic material for TACE
that doxorubicin can be loaded to. The tumor response rate of this well-tolerated
treatment was changed between 60% and 81.8%. We report a case of ischemic
cholecystitis after TACE with drug-eluting beads (DEB) that required
cholecystectomy. The possibility of cholecystitis is always remembered during
TACE-DEB for tumors in segment IV and/or V. Although selective catheterization is
related with a lower risk for ischemic cholecystitis, the anatomic and vascular
variability in patients with malignancy may lead to some unexpected conditions.
PMID- 23154027
TI - Ectopic intracaval liver.
AB - Congenital abnormalities of the liver are rare with prior descriptions of lobar
or segmental agenesis, Reidel's lobe, and ectopic hepatic lobes. Intrathoracic
ectopic hepatic lobes have been reported in many instances; however, there is
only one documented case of abnormally positioned liver tissue within the
inferior vena cava (J Chapman-Fredricks, R Birusingh, M Ricci, M Rodriguez,
Intracaval liver with cardiac extension. A new developmental anomaly? Fetal and
Pediatric Pathology. 2010; 29:401-406). We report a second case of an ectopic
intracaval liver defined as a mass in an adult who presented for abdominal pain
and review the radiological findings.
PMID- 23154026
TI - Heparin-induced thrombocytopenia (HIT) causing portosplenic, superior mesenteric,
and splenic vein thrombosis resulting in splenic rupture and pulmonary emboli
formation.
AB - Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of
heparin administration. Of the few reported cases of HIT-associated intra
abdominal thrombosis, none to our knowledge provide multidetector-row computed
tomography (MDCT) imaging findings or emphasize its utility in diagnosis. We
describe a case of HIT with MDCT images demonstrating extensive intra-abdominal
thrombosis and end-organ complications including splenic rupture and pulmonary
emboli. This case emphasizes the potential role of MDCT in the rapid detection of
HIT-related thromboembolic complications in patients with nonspecific abdominal
pain.
PMID- 23154028
TI - An unusual Hodgkin's lymphoma case presenting with upper extremity multiple
masses.
AB - Almost always, Hodgkin's lymphoma presents with lymph node involvement. Primary
extranodal lymphoma is rare and mostly has a type of non-Hodgkin's lymphoma. We
present an unusual presentation of a Hodgkin's lymphoma in a 33-year-old man.
There were numerous soft tissue masses localized in the subcutaneous tissue of
the left arm along the neurovascular bundle and the ipsilateral axillary region.
We found only one Hodgkin's lymphoma case that presented as an upper extremity
mass reported in the literature. In cases where a great number of successively
lined up soft tissue masses are detected on the extremity, lymphoma takes place
among the differential diagnoses.
PMID- 23154029
TI - Imaging findings of Nasu-Hakola disease: a case report.
AB - Nasu-Hakola disease (NHD), also known as polycystic lipomembranous osteodysplasia
and sclerosing leukoencephalopathy, is a rare and fatal hereditary disease with
less than 200 cases reported in the literature [Madry H, Prudlo J, Grgic A,
Freyschmidt J. Nasu-Hakola disease (PLOSL): report of five cases and review of
the literature. Clin Orthop Relat Res 2007;454:262-269]. This progressive disease
is characterized by multiple cystic bone lesions, complicated with pathologic
fractures and progressive dementia. Here in this article we report the imaging
findings including magnetic resonance imaging of a newly diagnosed NHD case, with
emphasis on the awareness of the radiologist for prompt recognition of this rare
entity.
PMID- 23154030
TI - Giant intradural extramedullary spinal hydatid cyst--a rare presentation.
AB - The hydatidosis, or echinococcosis, has a characteristic geographic distribution,
occurring most frequently in sheep-raising regions in Mediterranean, Central
Asian, and South American countries and in Australia. Spinal hydatidosis is very
rare, and intradural location is a rarer category of spinal hydatidosis. We
report a case of intradural extramedullary spinal hydatid cyst in a 9-year-old
boy. On magnetic resonance imaging, an intradural extramedullary giant cystic
lesion was seen mimicking an arachnoid cyst. However, endemic origin of the
patient and positive serology helped to make the diagnosis of hydatid cyst, which
was confirmed on postoperative histopathology.
PMID- 23154031
TI - Inelastic and elastic mean free paths from FIB samples of metallic glasses.
AB - We have used focused ion beam (FIB) milling and scanning electron microscopy
(SEM) to prepare samples of known thickness for measurement of the electron
scattering elastic and inelastic mean free paths (EMFP and IMFP respectively) of
three metallic glasses, Cu(64.5)Zr(35.5), Zr(50)Cu(45)Al(5), and
Al(87)Y(7)Fe(5)Cu. After measuring the EMFP and IMFP in a scanning transmission
electron microscope, we used the FIB to coat the lamellae with carbon on the top
and bottom surfaces, which eliminated secondary electron emission from those
surfaces and made SEM measurements of their thickness more reliable. At 200 kV,
we find IMFP/ EMFP values of 146+/-2/43+/-1, 163+/-1/41+/-1, and 149+/-1/85+/-1
nm, respectively for the three glass compositions. Our results differ from
available models for the IMFP by as much as 50%.
PMID- 23154032
TI - Variable magnification dual lens electron holography for semiconductor junction
profiling and strain mapping.
AB - Dual lens operation for electron holography, which was developed previously (Wang
et al., Ultramicroscopy 101 (2004) 63-72; US patent: 7,015,469 B2 (2006)), is re
investigated for bright field (junction profiling) and dark field (strain
mapping) electron holography using FEI instrumentation (i.e. F20 and Titan). It
is found that dual lens operation provides a wide operational range for electron
holography. In addition, the dark field image tilt increases at high objective
lens current to include Si <004> diffraction spot. Under the condition of high
spatial resolution (1 nm fringe spacing), a large field of view (450 nm), and
high fringe contrast (26%) with dual lens operation, a junction map is obtained
and strain maps of Si device on <220> and <004> diffraction are acquired. In this
paper, a fringe quality number, N', which is number of fringe times fringe
contrast, is proposed to estimate the quality of an electron hologram and
mathematical reasoning for the N' number is provided.
PMID- 23154033
TI - Quantifying the low-energy limit and spectral resolution in valence electron
energy loss spectroscopy.
AB - While the development of monochromators for scanning transmission electron
microscopes (STEM) has improved our ability to resolve spectral features in the 0
5 eV energy range of the electron energy loss spectrum, the overall benefits
relative to unfiltered microscopes have been difficult to quantify. Simple curve
fitting and reciprocal space models that extrapolate the expected behavior of the
zero-loss peak are not enough to fully exploit the optimal spectral limit and can
hinder the ease of interpreting the resulting spectra due to processing-induced
artifacts. To address this issue, here we present a quantitative comparison of
two processing methods for performing ZLP removal and for defining the low-energy
spectral limit applied to three microscopes with different intrinsic emission and
energy resolutions. Applying the processing techniques to spectroscopic data
obtained from each instrument leads in each case to a marked improvement in the
spectroscopic limit, regardless of the technique implemented or the microscope
setup. The example application chosen to benchmark these processing techniques is
the energy limit obtained from a silicon wedge sample as a function of thickness.
Based on these results, we conclude on the possibility to resolve statistically
significant spectral features to within a hundred meV of the native instrumental
energy spread, opening up the future prospect of tracking phonon peaks as new and
improved hardware becomes available.
PMID- 23154034
TI - The tibial crest as a practical useful landmark in total knee arthroplasty.
AB - BACKGROUND: The middle one-third of the tibial crest in the coronal plane and the
fibula in the sagittal plane are known as landmarks for extramedullary guides in
total knee arthroplasty (TKA). However, there are few foundational anatomic
studies about them. We conducted this study to confirm whether these landmarks
are reliable. METHODS: We evaluated 100 Japanese knees using 3D imaging software.
We examined our data for correlations between the angle of deviation from the
mechanical axis and patient-specific factors (i.e. hip-knee-ankle angle, tibial
length, tibial bowing, and tibial torsion) to determine whether there are any
individual factors affecting their reliability. RESULTS: The mean angles between
each of the axes defined by the fibula and the tibial crest with the mechanical
axis were 2.9 degrees +/-0.6 degrees of valgus and 0.7 degrees +/-0.9 degrees
of varus in the coronal plane and 2.2 degrees +/-0.8 degrees of posterior and
3.6 degrees +/-1.0 degrees of anterior inclination in the sagittal plane. The
middle one-third of the tibial crest (TCL) was revealed as a useful landmark,
especially in female patients, who possess TCLs that were within 3 degrees of
the tibial mechanical axis in the coronal plane. There were no patient-specific
factors strongly affecting reliability of these landmarks. CONCLUSIONS: We can
use these landmarks even if the patient has tibial bowing or severe varus
deformity. Although not considering soft tissue thickness, our study demonstrated
that the tibial crest in the coronal and sagittal planes could be useful
guidelines in performing TKAs. LEVEL OF EVIDENCE: II.
PMID- 23154035
TI - Report of ganglion cyst in the anterior cruciate ligament of a 6-year-old child.
AB - BACKGROUND: Intra-articular ganglion cysts of the knee are extremely rare within
the pediatric population. To our knowledge, only seven case reports have been
published in the medical literature identifying pediatric patients with intra
articular cysts of the anterior cruciate ligament (ACL). Intra-articular cysts of
the knee are a rare cause of knee discomfort and mechanical symptoms such as
locking of the knee. To our knowledge, up until now the youngest patient reported
in the medical literature with an intra-articular ganglion cyst of the ACL was a
7-year-old boy. CASE REPORT: We describe a 6-year-old boy who presented with a
unilateral intra-articular ganglion cyst of the ACL in the right knee. In
addition to the diagnostic work-up of radiographs and MRI, the cyst was
successfully treated with arthroscopic resection and debridement to decompress
the cyst. CLINICAL RELEVANCE: We provide a review of the proposed pathogenesis,
diagnostic modalities, differential diagnosis, treatment options, and
complications of treatment for intra-articular cysts of the ACL. LEVEL OF
EVIDENCE: Level V, case report.
PMID- 23154036
TI - Periprosthetic bone mineral density changes after unicondylar knee arthroplasty.
AB - BACKGROUND: Unicompartmental knee arthroplasty (UKA) has received renewed
interest in the last decade. UKA involves minor injury to soft tissues, limited
removal of bone and delicate preservation of knee anatomy and geometry. In
theory, UKA provides an opportunity to restore post-surgical knee kinematics to
near normal. HYPOTHESIS: UKA leaves patellofemoral joint free to meet high
mechanical forces with no stress-shielding and therefore might preserve bone
mineral density (BMD). PATIENTS AND METHODS: We studied 21 patients with
osteoarthritis (OA), who had received medial compartment UKA at Kuopio University
Hospital between October 1997 and September 2000. BMD was measured by dual-energy
X-ray absorptiometry (DEXA), at baseline (within a week after surgery) and at
intervals until 7 years. RESULTS: DEXA results were reproducible. The highest
rate of periprosthetic bone loss occurred during the first 3 months after UKA.
The average loss in BMD was 4.4% (p = 0.039) in the femoral diaphysis and it
ranged from 11.2% (p < 0.001) to 11.9% (p = 0.002) in the distal femoral
metaphysis; however, BMD changes in these regions, from 2 years to 7 years, were
nonsignificant. At the 1-year follow-up, the BMD of the medial tibial metaphysis
had increased by 8.9% (p = 0.02), whereas those in the lateral tibial metaphysial
(-2.4%) and diaphysial regions (-2.0%) did not change significantly.
INTERPRETATIONS: UKA did not preserve periprosthetic BMD in the distal femoral
metaphysis, whereas BMD changes in the tibial metaphysis were minor, consistent
with a mechanical balance between the medial and lateral tibial compartments.
LEVEL OF EVIDENCE 2B: Prospective case control study.
PMID- 23154037
TI - Antioxidant and antigenotoxic effects of lycopene in obstructive jaundice.
AB - BACKGROUND: Obstructive jaundice, a frequently observed condition caused by
obstruction of the common bile duct or its flow and seen in many clinical
situations, may end up with serious complications like sepsis, immune depression,
coagulopathy, wound breakdown, gastrointestinal hemorrhage, and hepatic and renal
failures. Intrahepatic accumulation of reactive oxygen species is thought to be
an important cause for the possible mechanisms of the pathogenesis of cholestatic
tissue injury from jaundice. Carotenoids have been well described that are able
to scavenge reactive oxygen species. Lycopene, a carotenoid present in tomatoes,
tomato products, and several fruits and vegetables, have been suggested to have
antioxidant activity, so may play a role in certain diseases related to the
oxidative stress. The aim of the present study was to determine the effects of
lycopene on oxidative stress and DNA damage induced by experimental biliary
obstruction in Wistar albino rats. MATERIALS AND METHODS: Daily doses of 100
mg/kg lycopene were given to the bile duct-ligation (BDL) rats orally for 14
days. DNA damage was evaluated by an alkaline comet assay. The levels of
aspartate transferase, amino alanine transferase, gamma glutamyl transferase,
alkaline phosphatase, and direct bilirubin were analyzed in plasma for the
determination of liver functions. The levels of malondialdehyde, reduced
glutathione, nitric oxide, catalase, superoxide dismutase, and glutathione S
transferase were determined in the liver and kidney tissues. Pro-inflammatory
cytokine tumor necrosis factor-alpha level was determined in the liver tissues.
Histologic examinations of the liver and kidney tissues were also performed.
RESULTS: According to this study, lycopene significantly recovered the parameters
of liver functions in plasma, reduced malondialdehyde and nitric oxide levels,
enhanced reduced glutathione levels, as well as enhancing all antioxidant enzyme
activity in all tissues obtained from the BDL group. Moreover, the parameters of
DNA damage in the liver and kidney tissue cells, whole blood cells, and
lymphocytes were significantly lower in the lycopene-treated BDL group, compared
with the BDL group. CONCLUSIONS: Lycopene significantly reduced the DNA damage,
and markedly recovered the liver and kidney tissue injuries seen in rats with
obstructive jaundice.
PMID- 23154038
TI - Hepatic amyloidosis: morphologic spectrum of histopathological changes in AA and
nonAA amyloidosis.
AB - In hepatic amyloidosis (HA), the relationships between the pattern and extent of
amyloid deposition, morphologic changes, associated diseases and clinical data
have not yet been demonstrated. In this study, we sought the correlation between
the above mentioned parameters in HA. Liver biopsies of 34 HA were
retrospectively analyzed for the type, distribution, and intensity of amyloid
deposition and associated morphologic changes. AA and nonAA types were classified
on the basis of immunohistochemistry. Follow-up clinical and laboratory findings
were reviewed. Twenty-three out of 34 patients (67.6%) had AA, and 11 out of 34
patients (32.4%) had nonAA amyloidosis. The predominant localization pattern in
AA amyloidosis was vascular (91.3%), and in nonAA amyloidosis it was mixed with
other patterns (72.7%). We confirmed that nonAA amyloid involves the hepatic
artery, as well as the portal and central vein, but deposition occurred more
frequently in the sinusoidal areas. We detected a portal stromal pattern only in
cases of nonAA amyloidosis with a mixed pattern of amyloid deposition. The
pattern of amyloid deposition in liver differs between the AA and nonAA type
amyloidosis. The distribution of amyloid within the liver is not a reliable
method for distinguishing AA from nonAA amyloidosis. However, the histological
pattern provides strong clues as to the etiology of the amyloid deposits, and
could provide information on the clinical status and prognosis of these patients.
PMID- 23154039
TI - A historical perspective on the development of the cytarabine (7days) and
daunorubicin (3days) treatment regimen for acute myelogenous leukemia: 2013 the
40th anniversary of 7+3.
AB - This paper reviews the development of therapy for acute myelogenous leukemia that
in 1973 led to the regimen of 7days of continuous intravenous arabinosylcytosine
(cytarabine) and the first 3 concurrent days of intravenous daunorubicin, given
the nickname "7+3." The state of leukemia treatment in the 1950s, 1960s and early
1970s is reviewed, the discovery of the two drugs in question described, and the
introduction of clinical trials to reach an optimal regimen for their use
delineated. During the 1950s, following World War Two and after a period of civil
reconstitution, a national effort, facilitated by the U.S. Congress and federal
investments in the National Cancer Institute, was initiated to enhance cancer
therapy in the United States. The development of mouse models of leukemia and
advances in understanding the structure and function of DNA and RNA and the
process of cell proliferation provided new targets for drug development and new
concepts for their use. The year, 2013, marks the 40th year that this protocol,
7+3, is the method of induction of remission for most patients with acute
myelogenous leukemia. Its inadequacies also are made clear. Many patients with
the disease die soon after diagnosis, and patients who have more unfavorable
oncogenetic subtypes, intrinsically drug resistant cells, and greater intolerance
to therapy make up the vast majority of the affected and few are cured. It is
evident to all that new paradigms are needed if acute myelogenous leukemia is to
be subdued in most patients with the disease.
PMID- 23154041
TI - CHiC, a new tandem affinity tag for the protein purification toolbox.
AB - In the present work we have constructed a new tandem affinity purification tag
and used it to purify two different polypeptides, PcsB and ECL1 from
Streptococcus pneumoniae. PcsB probably functions as a peptidoglycan hydrolase
and is believed to be involved in splitting of the septum during cell division.
ECL1 is the extracellular domain of the membrane spanning protein FtsX.
Experimental evidence indicates that the ECL1 domain controls the activity of
PcsB through direct interaction (Sham et al., 2011). The affinity tag consists of
an N-terminal 6xHis-tag, a choline binding domain followed by a proteolytic site
specific for the TEV (tobacco etch virus) endopeptidase. Based on the choline
binding His-tag combination the new 16.5 kDa tag was named CHiC. CHiC-tagged PcsB
and ECL1 were expressed in Escherichia coli and sequentially purified by
employing diethylaminoethyl-cellulose affinity chromatography and Ni(2+)
immobilized metal affinity chromatography. After TEV digestion, the CHiC-tag, TEV
protease and undigested fusion protein were easily separated from the target
protein in a single purification step. By using this method, 4-7 mg of
recombinant PcsB and ECL1 were obtained from one liter of cell culture with a
purity estimated to be at least 95%. In addition, we found that the tag has the
potential to function as a solubilisation partner as it markedly increased the
solubility of PcsB. In sum, the CHiC-tag is a versatile tool that allows
purification of milligram quantities of highly purified recombinant protein in
only one or two steps.
PMID- 23154040
TI - Visual attentional engagement deficits in children with specific language
impairment and their role in real-time language processing.
AB - In order to become a proficient user of language, infants must detect temporal
cues embedded within the noisy acoustic spectra of ongoing speech by efficient
attentional engagement. According to the neuro-constructivist approach, a multi
sensory dysfunction of attentional engagement - hampering the temporal sampling
of stimuli - might be responsible for language deficits typically shown in
children with Specific Language Impairment (SLI). In the present study, the
efficiency of visual attentional engagement was investigated in 22 children with
SLI and 22 typically developing (TD) children by measuring attentional masking
(AM). AM refers to impaired identification of the first of two sequentially
presented masked objects (O1 and O2) in which the O1-O2 interval was manipulated.
Lexical and grammatical comprehension abilities were also tested in both groups.
Children with SLI showed a sluggish engagement of temporal attention, and
individual differences in AM accounted for a significant percentage of unique
variance in grammatical performance. Our results suggest that an attentional
engagement deficit - probably linked to a dysfunction of the right fronto
parietal attentional network - might be a contributing factor in these children's
language impairments.
PMID- 23154042
TI - A rapid flow cytometric method for distinguishing between febrile bacterial and
viral infections.
AB - Antibiotic resistance due to the inappropriate use of antimicrobials is one of
the most critical public health problems worldwide. A major factor underlying the
unnecessary use of antibiotics is the lack of rapid and accurate diagnostic
tests. Therefore, we aimed to develop a novel rapid flow cytometric method for
distinguishing between febrile bacterial and viral infections. In this
prospective comparative study, quantitative flow cytometric analysis of
FcgammaRII/CD32, CR1/CD35, MHC Class I receptor (MHCI), and C5aR/CD88 on human
phagocytes was performed in 286 hospitalized febrile patients with suspected
infection. After using microbiological and serological detection methods, or
clinical diagnosis, 205 patients were identified with either bacterial (n=136) or
viral (n=69) infection. Receptor data from patients were compared to those of 50
healthy controls. We developed a flow cytometric marker of local and systemic
bacterial infections designated "bacterial infection score (BIS)" incorporating
the quantitative analysis of FcgammaRII/CD32, CR1/CD35, C5aR/CD88 and MHCI on
neutrophils and/or monocytes, which displays 91% sensitivity and 92% specificity
in distinguishing between microbiologically confirmed bacterial (n=77) and
serologically confirmed viral infections (n=61) within 1h. The BIS method was
effectively applied to distinguish between bacterial and viral (pandemic H1N1
influenza) pneumonia cases with 96% sensitivity and 92% specificity. We propose
that the rapid BIS test can assist physicians in deciding whether antibiotic
treatment is necessary, thus reducing unnecessary antimicrobial use.
PMID- 23154043
TI - The use of high-resolution melting analysis for rapid spa typing on methicillin
resistant Staphylococcus aureus clinical isolates.
AB - Methicillin-resistant Staphylococcus aureus (MRSA) has been endemic in Hong Kong
for three decades. This study evaluated the practical use of high-resolution
melting (HRM) real-time PCR analysis on MRSA staphylococcal Protein A (spa)
typing on local MRSA isolates. Among 55 clinical MRSA isolates collected in 2011,
12 different spa types were observed by the conventional PCR-sequencing method
including the locally predominant spa type t1081 and two locally predominant
community acquired MRSA spa types t019 and t437. By using the HRM method, it
could differentiate all 12 spa genotypes by distinct melting curves and HRM
difference plot analysis. These two methods demonstrated 100% concordance whereas
the HRM method required only 3h of turnaround time and one-fifth of reagent cost
compared to the conventional method. Our study confirmed that the cost effective
and rapid HRM typing approach is practically useful for MRSA community
transmission monitoring and nosocomial outbreak control in Hong Kong.
PMID- 23154044
TI - Use of MALDI-TOF mass spectrometry for identification of bacteria that are
difficult to culture.
AB - Rapid and reliable detection and identification of bacterial species are
necessary for diagnosis and efficient treatment. Until recently, bacterial
identification in clinical laboratories has mainly relied on conventional
phenotypic and gene sequencing identification techniques. The identification of
anaerobic bacteria, fastidious and slow growing bacteria using conventional
methods is time consuming, expensive and complicated. Many anaerobes grow poorly
or are nonreactive in most diagnostic systems. Unambiguous diagnosis of active
tuberculosis is a time-consuming process, requiring as long as 12 weeks for
positive identification of the organism. This long time frame presents challenges
for case identification. Early identification of pathogenic bacteria is very
important for the disease control. Recently, bacteriologists have focused their
attention on the use of mass spectrometry (MS) for bacterial identification,
especially Matrix Assisted Laser Desorption Ionization Time-Of-Flight (MALDI
TOF). Use of MALDI-TOF-MS is described in this review, with a special emphasis on
the successful identification of groups of bacteria, which are difficult to
culture. MALDI-TOF-MS is a powerful, rapid, precise, and cost-effective method
for identification of intact bacteria, compared to conventional phenotypic
techniques or molecular biology. Our review suggests that identification of
anaerobes, fastidious bacteria and slow growing bacteria, has been improved by
the arrival of MALDI-TOF-MS in clinical laboratories.
PMID- 23154045
TI - Assessment of intestinal microbiota modulation ability of Bifidobacterium strains
in in vitro fecal batch cultures from preterm neonates.
AB - Microbial colonization of the infant gut is essential for the development of the
intestine and the immune system. The intestinal microbiota of full-term breast
fed infants is considered as the health standard for newborns. A culture medium
containing formula milk was designed, which allowed a balanced growth of
intestinal microorganisms and was used to perform fecal batch cultures from
preterm babies. Sixteen Bifidobacterium strains and fructooligosaccharides (FOS)
were tested for their ability to modulate in vitro the intestinal microbiota. The
production of short chain fatty acids (SCFA) was measured by Gas Chromatography
and the levels of some anaerobe (Bifidobacterium and Bacteroides groups) and
facultative anaerobes (Enterobacteriaceae, Enterococcaceae, Weissella group, and
Klebsiella pneumoniae) were determined by quantitative PCR. Results were referred
to a fecal negative control culture without microorganisms or FOS added. Strains
that in fecal cultures counteracted better the aberrancies previously found in
feces of preterm babies, as compared with full-term breast-fed infants, were
selected. The three Bifidobacterium bifidum strains tested in this work promoted
the most suitable shifts in SCFA and in the ratio of variables facultative
anaerobes to anaerobes. Two Bifidobacterium breve strains complied with the
requirement for facultative anaerobes and anaerobes and one of them also promoted
a suitable shift of SCFA. Bifidobacteria behaved similarly as FOS regarding the
microbial profiles in fecal cultures but the production of lactic and acetic acid
was much lower. B. breve and B. bifidum strains selected represent promising
candidates for their assessment in more complex in vitro and in vivo models.
PMID- 23154046
TI - Pulmonary cryptococcosis in non-AIDS patients.
AB - OBJECTIVE: To investigate the clinical features, management, and prognosis of
pulmonary cryptococcosis in non-acquired immunodeficiency syndrome (AIDS)
patients. METHOD: 24 cases of pulmonary cryptococcosis with accurate pathological
diagnosis were retrospectively studied. RESULTS: 15 male patients and nine female
patients were diagnosed at the first affiliated hospital of Sun Yat-sen
University from November 1999 to November 2011. The mean age at the time of
diagnosis was 44.2+/-11.3 years (range: 24 to 65 years). Among these patients, 13
had other comorbidities. 15 were symptomatic and the other nine were
asymptomatic. The most common presenting symptoms were cough, chest tightness,
expectoration, and fever. None had concurrent cryptococcal meningitis. The most
frequent radiologic abnormalities on chest computed tomography (CT) scans were
solitary or multiple pulmonary nodules, and masses or consolidations, and most
lesions were located in the lower lobes. All patients had biopsies for the
accurate diagnosis. Among the 24 patients, nine patients underwent surgical
resections (eight had pneumonectomy via thoracotomy and one had a pneumonectomy
via thoracoscopy). Five of the patients who underwent surgery also received
antifungal drug therapy (fluconazole) for one to three months after the surgery.
The other 15 only received antifungal drug therapy (fluconazole or voriconazole)
for three to six months (five patients are still on therapy). The follow-up
observation of 19 patients who had already finished their treatments lasted from
two to 11 years, and there was no relapse, dissemination, or death in any of
these patients. CONCLUSION: Non-AIDS patients with pulmonary cryptococcosis have
a good prognosis with appropriate management.
PMID- 23154047
TI - Detection of bla(OXA-23) in Acinetobacter spp. isolated from patients of a
university hospital.
AB - INTRODUCTION: Acinetobacter spp. have emerged as notorious pathogens involved in
healthcare-associated infections. Carbapenems are important antimicrobial agents
for treating infections due to multidrug resistant Acinetobacter spp. Different
mechanisms may confer resistance to these drugs in the genus, particularly
production of class D carbapenemases. OXA-23-like family has been pointed out as
one of the predominant carbapenamases among Acinetobacter. The present work aimed
to investigate the occurrence of OXA-23-like carbapenemases among Acinetobacter
isolates recovered from patients of a university hospital in Niteroi, RJ, Brazil.
METHODS: Antimicrobial susceptibility profiles were determined by disk-diffusion.
Imipenem resistant isolates were submitted to Modified Hodge Test in order to
screen for carbapenemase production, and later to polymerase chain reaction (PCR)
to investigate the presence of bla(OXA-23). RESULTS: Imipenem and meropenem
resistance rates were 71.4% and 69.7%, respectively. The Modified Hodge Test
revealed carbapenemase production among 76 (89.4%) of the 85 imipenem resistant
isolates analyzed; according to PCR results, 81 isolates (95.4%) carried the
bla(OXA-23) gene. CONCLUSIONS: OXA-23-like enzymes may be an important mechanism
of carbapenem resistance among isolates present in the hospital studied.
PMID- 23154048
TI - [Dropped head syndrome: a case study in a geriatric patient].
PMID- 23154049
TI - Dementia and out-of-pocket spending on health care services.
AB - BACKGROUND: High levels of out-of-pocket (OOP) spending for health care may lead
patients to forego needed services and medications as well as hamper their
ability to pay for other essential goods. Because it leads to disability and the
loss of independence, dementia may put patients and their families at risk for
high OOP spending, especially for long-term care services. METHODS: We used data
from the Aging, Demographics, and Memory Study, a nationally representative
subsample (n = 743) of the Health and Retirement Study, to determine whether
individuals with dementia had higher self-reported OOP spending compared with
those with cognitive impairment without dementia and those with normal cognitive
function. We also examined the relationship between dementia and utilization of
dental care and prescription medications-two types of health care that are
frequently paid for OOP. Multivariate and logistic regression models were used to
adjust for the influence of potential confounders. RESULTS: After controlling for
demographics and comorbidities, those with dementia had more than three times the
yearly OOP spending compared with those with normal cognition ($8216 for those
with dementia vs. $2570 for those with normal cognition, P < .01). Higher OOP
spending for those with dementia was mainly driven by greater expenditures on
nursing home care (P < .01). Dementia was not associated with the likelihood of
visiting the dentist (P = .76) or foregoing prescription medications owing to
cost (P = .34). CONCLUSIONS: Dementia is associated with high levels of OOP
spending but not with the use of dental care or foregoing prescription
medications, suggesting that excess OOP spending among those with dementia does
not "crowd out" spending on these other health care services.
PMID- 23154050
TI - Alzheimer's disease pathology does not mediate the association between depressive
symptoms and subsequent cognitive decline.
AB - BACKGROUND: Depressive symptoms in nondemented individuals appear to hasten the
progression from mild cognitive impairment to clinical Alzheimer's disease (AD)
and double the risk of incident AD. However, the mechanism(s) by which depression
might affect this risk has not been well established. The purpose of this
analysis was to test the hypothesis that AD pathology mediates depression's
apparent effect on the risk of dementia conversion using longitudinally collected
psychometric testing and autopsy data from the Honolulu-Asia Aging Study.
METHODS: Latent factor variables representing AD, cortical Lewy body (CLB), and
ischemic neuropathology were tested as potential mediators of the association
between the Center for Epidemiological Studies depression scale (CES-D) score and
the 10-year prospective rate of cognitive decline, adjusted for baseline
cognition, age, education, total number of medications, and brain weight at
autopsy. RESULTS: CES-D scores, neurofibrillary tangle counts, CLB counts, and
ischemic lesions each made significant independent contributions to cognitive
decline. However, CES-D scores were not significantly associated with any
pathological variable; thus the pathological variables were not mediators of the
effect of CES-D scores on cognitive decline. CONCLUSIONS: Subsyndromal depressive
symptoms are significantly associated with subsequent cognitive decline. Although
the effect is relatively modest, it is stronger than that of amyloid-related
neuropathologies and independent of that of neurofibrillary tangles, cortical
Lewy bodies, and ischemic lesions. Our results argue against the role of AD
related neuropathology as a mediator of depression's effect on cognitive decline,
but cannot rule out a significant mediation effect in a subset of cases, perhaps
with more severe baseline depressive symptoms.
PMID- 23154051
TI - The synaptic proteome in Alzheimer's disease.
AB - BACKGROUND: Synaptic dysfunction occurs early in Alzheimer's disease (AD) and is
recognized to be a primary pathological target for treatment. Synapse
degeneration or dysfunction contributes to clinical signs of dementia through
altered neuronal communication; the degree of synaptic loss correlates strongly
with cognitive impairment. The molecular mechanisms underlying synaptic
degeneration are still unclear, and identifying abnormally expressed synaptic
proteins in AD brain will help to elucidate such mechanisms and to identify
therapeutic targets that might slow AD progression. METHODS: Synaptosomal
fractions from human autopsy brain tissue from subjects with AD (n = 6) and
without AD (n = 6) were compared using two-dimensional differential in-gel
electrophoresis. AD pathology is region specific; human subjects can be highly
variable in age, medication, and other factors. To counter these factors, two
vulnerable areas (the hippocampus and the temporal cortex) were compared with two
relatively spared areas (the motor and occipital cortices) within each group.
Proteins exhibiting significant changes in expression were identified (>=20%
change, Newman-Keuls P value < .05) using either matrix-assisted laser desorption
ionization time-of-flight or electrospray ionisation quadrupole-time of flight
mass spectrometry. RESULTS: Twenty-six different synaptic proteins exhibited more
than twofold differences in expression between AD and normal subjects. These
proteins are involved in regulating different cellular functions, including
energy metabolism, signal transduction, vesicle transport, structure, and
antioxidant activity. CONCLUSION: Comparative proteome analysis uncovered markers
of pathogenic mechanisms involved in synaptic dysfunction.
PMID- 23154052
TI - Brain, networks, depression, and more.
AB - Depression is a heterogeneous disorder with a highly variable course. Individual
responses to treatment are inconsistent, and an established mechanism remains
elusive. The classical hypothesis of depression posits that mood disorders are
caused by a chemical imbalance in the brain that can be corrected with
antidepressant drugs. However, recent evidence indicates that information
processing dysfunction within neural networks might underlie depression, and
antidepressant drugs induce plastic changes in neuronal connectivity that
gradually lead to improvements in neuronal information processing and recovery.
This review presents the major current approaches to understanding the biological
mechanisms of major depression, with a focus on complex brain networks.
PMID- 23154053
TI - ACCF 2012 expert consensus document on practical clinical considerations in the
interpretation of troponin elevations: a report of the American College of
Cardiology Foundation task force on Clinical Expert Consensus Documents.
PMID- 23154054
TI - Psychological factors associated with indices of risky, reckless and cautious
driving in a national sample of drivers in the Republic of Ireland.
AB - This paper presents the results of a national survey of drivers in the Republic
of Ireland that sought to examine psychological predictors of specific driving
behaviours. 1638 respondents attending National Car Testing (NCT) centres
nationwide completed a questionnaire battery that included personality,
attitudinal, locus of control and social influence measures. The driving
behaviours examined were drawn from a Driving Behaviour Scale (Iversen, 2004) and
included Speeding and Rule Violation, Reckless Driving, Wearing of Seat Belts,
Cautious Driving and Drink Driving. Cross-group comparisons suggested that males
engaged in more risky and less cautious driving behaviours than females, and
participants under the age of 25 were more risky and less cautious than those 25
years or older. Statistically significant models of each driving outcome emerged.
The best model fit was for speeding and rule violation, which was predicted by a
model including positive attitudes towards speeding, greater normative influences
of friends and higher perceived behavioural control, extraversion and driving
anger. These findings offer important insights into the correlates of different
driving behaviours and can help inform the work of road safety practitioners.
PMID- 23154055
TI - Resistance training improves cardiac output, exercise capacity and tolerance to
positive airway pressure in Fontan physiology.
AB - BACKGROUND: Subjects with Fontan-type circulation have no sub-pulmonary ventricle
and thus depend exquisitely on the respiratory bellows and peripheral muscle pump
for cardiac filling. We hypothesised that resistance training to augment the
peripheral muscle pump might improve cardiac filling, reduce inspiratory
dependence of IVC return to the heart and thus improve exercise capacity and
cardiac output on constant positive airway pressure (CPAP). METHODS: Eleven
Fontan subjects (32+/-2 years, mean+/-SEM) had cardiac magnetic resonance imaging
(MRI) and exercise testing (CPET); six underwent 20 weeks of high-intensity
resistance training; others were non-exercising controls. After training, CPET
was repeated. Four trainers had MRI with real-time flow measurement at rest,
exercise and on CPAP in the trained state and following a 12-month detrain.
RESULTS: In the trained state, muscle strength increased by 43% (p=0.002), as did
total muscle mass (by 1.94 kg, p=0.003) and peak VO2 (by 183 ml/min, p=0.02).
After detraining, calf muscle mass and peak workload had fallen significantly
(p<0.03 for both) as did peak VO2 (2.72 vs. 2.18 l/min, p<0.001) and oxygen
pulse, a surrogate for SV (16% lower, p=0.005). Furthermore after detraining, SV
on MRI decreased at rest (by 11 ml, p=0.01) and during moderate-intensity
exercise (by 16 ml, p=0.04); inspiratory-dependent IVC blood return during
exercise was 40% higher (p=0.02). On CPAP, cardiac output was lower in the
detrained state (101 vs. 77 ml/s, p=0.03). CONCLUSIONS: Resistance muscle
training improves muscle mass, strength and is associated with improved cardiac
filling, stroke volume, exercise capacity and cardiac output on CPAP, in adults
with Fontan-type circulation.
PMID- 23154056
TI - Cardioprotective molecules are enriched in beating cardiomyocytes derived from
human embryonic stem cells.
AB - BACKGROUND: Cardiomyocytes derived from human embryonic stem cells (hESC-CMs)
have attracted attention because of their cardiac regenerative potential in vivo.
Differentiated CMs can be distinguished into two different phenotypic
populations: beating and non-beating CMs. A thorough understanding of the
different molecular conditions of beating and non-beating CMs would provide
valuable information for other potential applications and cell therapy. METHODS:
In this study, we generated a comparative protein profiles using proteomic
analysis and western blotting, to compare the specific protein expression
patterns of beating and non-beating hESC-CMs. RESULTS: Abundantly 72 upregulated
proteins are involved in different biological processes such as stimulus
response, cellular catabolism and cell motility. Among these proteins, such as
HSPs and other antioxidant molecules, are known to be proteins that potentially
play an important role in cardioprotection through the enhancement of cell
survival in hypoxic and ischemic conditions present in the injured heart.
CONCLUSION: As a first step toward understanding the different molecular
conditions of beating and non-beating hESC-CMs, we sought to study their
differential expression patterns and discuss their relevance to in vivo
functioning in cardiac injury repair. Thus, the results of this study could
provide further evidence supporting a cardiac regenerative approach using an
optimized cell source derived from hESCs.
PMID- 23154057
TI - Interaction between hypertension and HSP70 variants increase the risk of cerebral
ischemia in Chinese Han population: an association study.
AB - Cerebral infarction has become one of the leading diseases and a major mortality
factor around the world. Atherosclerosis is recognized as one of the important
causes of ischemic stroke. Recently, accumulating evidences have indicated that
the anti-inflammatory and anti-apoptotic functions of the HSP70 family play an
important role in cerebral ischemia. However, the association between HSP70 SNPs
and ischemic stroke was also not well established. We chose 101 cases of cerebral
ischemia and 100 healthy people from the Chinese Han population as our study
subjects, and PCR-RFLP was employed to analyze HSP70 polymorphisms: HSP70
1+190G/C, HSP70-2+1267A/G and HSP70-hom+2437T/C. There were no significant
differences in +1267A/G allele or genotype frequencies between patients with
stroke and healthy controls. However, genotypes of +190CG and +2437TT were
differentially distributed between the patients and controls. A significant
difference of T allele distribution in the HSP70-hom+2437T/C site was observed.
Logistic regression analysis indicated that genotypes of +190CG, +2437TT and T
allele in HSP70-hom were risk factors of ischemic stroke. Moreover, the study has
formulated that the interactions between hypertension and +190CG or +2437TT may
increase the risks of ischemic stroke. The results from this study have suggested
a clinical indicator for assessing the possibilities of cerebral stroke, and
supply basis to clinicians to give precaution to people who are at risk of
stroke.
PMID- 23154058
TI - Epilepsy in adult X-linked adrenoleucodystrophy due to the deletion c.1415
1416delAG in exon 5 of the ABCD1-gene.
AB - Seizures in cerebral X-linked adrenoleucodystrophy (X-ALD) more frequently occur
in the early-onset compared to the late-onset form. Here we describe an adult in
whom X-ALD deteriorated after head trauma and who developed epilepsy with
progression of X-ALD. In a 50 year-old Caucasian male, cerebral X-ALD was
diagnosed upon progressive gait disturbance, intellectual decline, elevated very
long chain fatty acids in the serum or leucocytes, cerebral MRI, showing
extensive, symmetric, homogenous demyelination in the parieto-occipital areas,
the splenium corporis callosum, the thalamus, the crura cerebri, the brain stem,
and the pedunculi cerebelli, and the deletion c.1415-1416delAG in the ABCD1-gene.
After a head trauma the phenotype deteriorated to mutism, dysphagia, and severe
spastic quadruparesis. At an age of 50 years the patient experienced his first,
self-limiting, tonic-clonic seizure during an infection, which is why valproic
acid was started. Recurrence of seizures after discharge required repeated
adaptation of the valproic acid-dosage. Adult X-ALD may be associated with late
onset seizures, which respond favourably to valproic acid. Since any type of
seizure episode in adult-onset cerebral X-ALD is usually followed by neurological
decline, prophylactic treatment with antiepileptic drugs should be considered not
only in early-onset but also in adult-onset epilepsy in X-ALD.
PMID- 23154059
TI - Localization of germline marker vasa homolog RNA to a single blastomere at early
cleavage stages in the oriental river prawn Macrobrachium nipponense: evidence
for germ cell specification by preformation.
AB - Germ cells are specified by the inheritance of maternal germline determinants
(preformation mode) or inductive signals from somatic cells (epigenesis mode)
during embryogenesis. However, the germline specification in decapod crustaceans
is unclear so far. Using vasa homolog (MnVasa) as a germ cell marker, here we
probed the early events of germline specification in the oriental river prawn
Macrobrachium nipponense. Quantitative RT-PCR analysis of unfertilized eggs and
embryos demonstrated that the prawn MnVasa mRNA is a maternal factor. Whole-mount
in situ hybridization further indicated that MnVasa transcripts are maternally
supplied to only one blastomere at the very early cleavage stages. As cleavage
proceeds, the MnVasa-positive blastomere undergoes proliferation and increases in
number. During gastrulation, the MnVasa-positive cells are found to be around a
blastopore and could migrate into an embryo through the blastopore. At the zoea
stage, clusters of the MnVasa-positive cells distribute not only in the gonad
rudiment in the cephalothorax but also at an extragonadic site, dorsal to the
posterior hindgut in the abdomen, suggesting that MnVasa-positive cells could
migrate anteriorly to the genital rudiment through the hindgut. Based on the
dynamic localization and number of MnVasa-positive cells during embryogenesis, we
concluded that the MnVasa-positive cells are primordial germ cells (PGC) or
founder cells of PGC that are separated from soma at the early cleavage stage.
MnVasa mRNA might have a key function in the specification of the prawn germline
cells as a maternal determinant. These results provide the first evidence that
the germline specification in decapod crustaceans follows a preformation mode.
PMID- 23154060
TI - Molecular characterization and expression analysis of ubiquitin-activating enzyme
E1 gene in Citrus reticulata.
AB - Ubiquitin-activating enzyme E1 (UBE1) catalyzes the first step in the
ubiquitination reaction, which targets a protein for degradation via a proteasome
pathway. UBE1 plays an important role in metabolic processes. In this study, full
length cDNA and DNA sequences of UBE1 gene, designated CrUBE1, were obtained from
'Wuzishatangju' (self-incompatible, SI) and 'Shatangju' (self-compatible, SC)
mandarins. 5 amino acids and 8 bases were different in cDNA and DNA sequences of
CrUBE1 between 'Wuzishatangju' and 'Shatangju', respectively. Southern blot
analysis showed that there existed only one copy of the CrUBE1 gene in genome of
'Wuzishatangju' and 'Shatangju'. The temporal and spatial expression
characteristics of the CrUBE1 gene were investigated using semi-quantitative RT
PCR (SqPCR) and quantitative real-time PCR (qPCR). The expression level of the
CrUBE1 gene in anthers of 'Shatangju' was approximately 10-fold higher than in
anthers of 'Wuzishatangju'. The highest expression level of CrUBE1 was detected
in pistils at 7days after self-pollination of 'Wuzishatangju', which was
approximately 5-fold higher than at 0 h. To obtain CrUBE1 protein, the full
length cDNA of CrUBE1 genes from 'Wuzishatangju' and 'Shatangju' were
successfully expressed in Pichia pastoris. Pollen germination frequency of
'Wuzishatangju' was significantly inhibited with increasing of CrUBE1 protein
concentrations from 'Wuzishatangju'.
PMID- 23154061
TI - Molecular characterization and genetic variability at kappa-casein gene (CSN3) in
camels.
AB - kappa-casein is a glycosilated protein belonging to a family of phosphoproteins
(alphas1, beta, alphas2, kappa) that represent the major protein component in
mammalian milk. kappa-casein plays an essential role in the casein micelle
stabilization, determining the size and the specific function. In the present
paper, we report for the first time the characterization of the nucleotide
sequence of the whole kappa-casein-encoding gene (CSN3) plus 1045 nucleotides at
the 5' flanking region in Camelus dromedarius. The promoter region and the
complete cDNA were also provided for the first time in Camelus bactrianus. The
gene is spread over 9.3kb and consists of 5 exons varying in length from 33bp
(exon 3) to 494bp (exon 4), and 4 introns from 1200bp (intron 3) to 2928bp
(intron 2). Highly conserved sequences, located in the 5' flanking region, have
been found. The regulatory regions of camels seems to be more related to equids
than to other compared species. 17 polymorphic sites have been detected, one of
these (g.1029T>C) is responsible for the creation of a new putative consensus
sequence for the transcription factor HNF-1. In general, these SNPs are the first
reported in camels for casein loci. Finally, seven interspersed repeated elements
were also identified at intronic level.
PMID- 23154062
TI - Functional and evolutionary analysis of DXL1, a non-essential gene encoding a 1
deoxy-D-xylulose 5-phosphate synthase like protein in Arabidopsis thaliana.
AB - The synthesis of 1-deoxy-D-xylulose 5-phosphate (DXP), catalyzed by the enzyme
DXP synthase (DXS), represents a key regulatory step of the 2-C-methyl-D
erythritol 4-phosphate (MEP) pathway for isoprenoid biosynthesis. In plants DXS
is encoded by small multigene families that can be classified into, at least,
three specialized subfamilies. Arabidopsis thaliana contains three genes encoding
proteins with similarity to DXS, including the well-known DXS1/CLA1 gene, which
clusters within subfamily I. The remaining proteins, initially named DXS2 and
DXS3, have not yet been characterized. Here we report the expression and
functional analysis of A. thaliana DXS2. Unexpectedly, the expression of DXS2
failed to rescue Escherichia coli and A. thaliana mutants defective in DXS
activity. Coherently, we found that DXS activity was negligible in vitro, being
renamed as DXL1 following recent nomenclature recommendation. DXL1 is targeted to
plastids as DXS1, but shows a distinct expression pattern. The phenotypic
analysis of a DXL1 defective mutant revealed that the function of the encoded
protein is not essential for growth and development. Evolutionary analyses
indicated that DXL1 emerged from DXS1 through a recent duplication apparently
specific of the Brassicaceae lineage. Divergent selective constraints would have
affected a significant fraction of sites after diversification of the paralogues.
Furthermore, amino acids subjected to divergent selection and likely critical for
functional divergence through the acquisition of a novel, although not yet known,
biochemical function, were identified. Our results provide with the first
evidences of functional specialization at both the regulatory and biochemical
level within the plant DXS family.
PMID- 23154063
TI - Akt1 as a putative regulator of Hox genes.
AB - In mammals, precise spatiotemporal expressions of Hox genes control the main body
axis during embryogenesis. However, the mechanism by which Hox genes are
regulated is poorly understood. To discover the putative regulator of Hox genes,
in silico analyses were performed using GEO profiles, and Akt1 emerged as a
candidate regulator of Hox genes in E13.5 MEFs. The results of the RT-PCR showed
that 5' Hoxc genes, including ncRNA were upregulated in Akt1 null MEF. Combined
bisulfite restriction analysis (COBRA) and bisulfite sequencing showed that the
CpG island of a 5' Hoxc gene was hypomethylated in Akt1 null cells. These results
indicate that Hox expression could be controlled by the function of Akt1 through
epigenetic modification such as DNA methylation.
PMID- 23154064
TI - In utero and childhood polybrominated diphenyl ether (PBDE) exposures and
neurodevelopment in the CHAMACOS study.
AB - BACKGROUND: California children's exposures to polybrominated diphenyl ether
flame retardants (PBDEs) are among the highest worldwide. PBDEs are known
endocrine disruptors and neurotoxicants in animals. OBJECTIVE: Here we
investigate the relation of in utero and child PBDE exposure to neurobehavioral
development among participants in CHAMACOS (Center for the Health Assessment of
Mothers and Children of Salinas), a California birth cohort. METHODS: We measured
PBDEs in maternal prenatal and child serum samples and examined the association
of PBDE concentrations with children's attention, motor functioning, and
cognition at 5 (n = 310) and 7 years of age (n = 323). RESULTS: Maternal prenatal
PBDE concentrations were associated with impaired attention as measured by a
continuous performance task at 5 years and maternal report at 5 and 7 years of
age, with poorer fine motor coordination-particularly in the nondominant-at both
age points, and with decrements in Verbal and Full-Scale IQ at 7 years. PBDE
concentrations in children 7 years of age were significantly or marginally
associated with concurrent teacher reports of attention problems and decrements
in Processing Speed, Perceptual Reasoning, Verbal Comprehension, and Full-Scale
IQ. These associations were not altered by adjustment for birth weight,
gestational age, or maternal thyroid hormone levels. CONCLUSIONS: Both prenatal
and childhood PBDE exposures were associated with poorer attention, fine motor
coordination, and cognition in the CHAMACOS cohort of school-age children. This
study, the largest to date, contributes to growing evidence suggesting that PBDEs
have adverse impacts on child neurobehavioral development.
PMID- 23154066
TI - Neonatal outcome and congenital malformations in children born after ICSI with
testicular or epididymal sperm: a controlled national cohort study.
AB - STUDY QUESTION: Does neonatal outcome including congenital malformations in
children born after ICSI with epididymal and testicular sperm [testicular sperm
extraction (TESE)/percutaneous epididymal sperm aspiration (PESA)/testicular
sperm aspiration (TESA) (TPT)] differ from neonatal outcome in children born
after ICSI with ejaculated sperm, IVF and natural conception (NC)? SUMMARY
ANSWER: Children born after TPT have similar neonatal outcome, including total
malformation rates, as have children born after ICSI and IVF with ejaculated
sperm. Testing for variance over the four groups may indicate smaller differences
in specific malformation rates with TPT as the highest risk group. WHAT IS KNOWN
ALREADY: Regarding neonatal outcome as well as congenital malformations in
children born after TPT, studies are few, with limited sample size, heterogeneous
and often performed without relevant control groups. STUDY DESIGN, SIZE,
DURATION: Population-based cohort study including all Danish children born after
TPT and fresh embryo transfer in Denmark from 1995 to 2009. Children born after
transfer of frozen-thawed embryos were excluded. Control groups of children
conceived by ICSI with ejaculated sperm, IVF and NC were identified by cross
linkage of the Danish IVF Register, Medical Birth Register (MBR) and National
Hospital Discharge Register (HDR). PARTICIPANTS/MATERIALS, SETTING: The study
group consisted of 466 children born after TPT, while the control groups
consisted of 8967 (ICSI with ejaculated sperm), 17 592 (IVF) and 63 854 (NC)
children. Neonatal outcomes and congenital malformations were analysed for
singletons and twins separately. Risk estimates for low birthweight (LBW, <2500
g) and preterm birth (PTB, <37 gestational weeks) were adjusted for maternal age,
parity, child gender and year of childbirth. The study group was identified from
the Danish national database on children born after TPT. Control groups were
obtained from the IVF register and the MBR. All information included in the study
was retrieved from the national registers. MAIN RESULTS AND THE ROLE OF CHANCE:
Considering singletons and twins as one group, the sex ratio (?/?) was
significantly lower for children born after TPT (0.89) compared with conventional
IVF (1.11; P = 0.017) but did not differ significantly when compared with ICSI
with ejaculated sperm (0.94) and NC (1.05). The mean birthweight (BW) for
singletons did not differ significantly between groups when including only first
born children. The mean gestational age (GA) in the TPT singletons (279 +/- 12
days) was significantly higher compared with IVF (276 +/- 18 days; P = 0.02), but
similar to ICSI with ejaculated sperm and NC singletons when including only first
born children (277 +/- 16 days and 279 +/- 14 days, respectively). Rate of
stillbirths, perinatal and neonatal mortality in the group of TPT singletons did
not differ significantly from any of the control groups. Comparable results were
found for the TPT twin group, except for perinatal mortality, which was
significantly lower in the TPT group compared with naturally conceived twins. The
adjusted risk of LBW was significantly higher for TPT versus NC singletons
[adjusted odds ratio (AOR) = 0.67 (0.48-0.93)]; however AOR for PTB was similar
in the two groups. Regarding twins, similar adjusted risks were observed for PTB
and LBW between the TPT and all three control groups. Significantly more
Caesarean sections were performed after IVF (27.3% for singletons) and ICSI
(25.1% for singletons) with ejaculated sperm compared with the TPT group (16.4%
for singletons). The total rate of congenital malformations in the TPT group was
7.7% and did not differ significantly from any of the control groups. However,
singleton TPT boys showed an increased rate of cardiac malformations (3.6%)
compared with singleton boys after IVF (1.4%; P = 0.04) and NC (1.1%; P = 0.02).
Considering the level of male infertility as a continuum over the four groups,
tests for variance in the rate of cardiac malformations in singleton boys, and
undescended testicles for singleton as well as twin boys were each significantly
increased from NC to IVF to ICSI to TPT (P < 0.001). The rate of hypospadias
showed the same pattern, but the TPT group did not differ significantly compared
with the control groups. LIMITATIONS, REASONS FOR CAUTION: One of the limitations
is that the TPT group could not be classified according to testicular or
epididymal sperm, as these data were not available in the IVF register. Another
limitation is that registry-based studies are encumbered with the risk of
reporting or coding errors or missing data due to insufficient coding. However,
the quality of data on congenital malformations in HDR has, in other studies,
been validated and found acceptable for epidemiological research, and
furthermore, recordings on study and control groups are performed similarly.
WIDER IMPLICATIONS OF THE FINDINGS: Accumulating data show that TPT treatment is
equally safe as conventional ICSI and IVF treatment and as NC with regard to
neonatal outcome including congenital malformation. STUDY FUNDING/POTENTIAL
COMPETING INTERESTS: This study is supported by Laboratory of Reproductive
Biology, Scientific Unit, Horsens Hospital. No competing interests declared.
PMID- 23154067
TI - Age at menopause and its influencing factors in a cohort of survivors of
childhood cancer: earlier but rarely premature.
AB - STUDY QUESTION: Is the age at menopause in a cohort of childhood cancer survivors
earlier and what are the risk factors associated with earlier age at menopause?
SUMMARY ANSWER: Menopause occurred at a median age of 44 years in this cohort
which is earlier than in the general population, but premature menopause was
uncommon. Main risk factors for non-surgical menopause were exposure to and dose
of alkylating agents, especially during adolescence, radiation dose to the
ovaries and oophorectomy. WHAT IS KNOWN ALREADY: While survivors of childhood
cancer are known to be at increased risk for developing premature menopause, data
on its risk factors are limited. STUDY DESIGN: A cohort study of 1109 still
living female survivors of childhood solid cancer treated between 1945 and 1985,
of whom 863 (78%) returned a follow-up questionnaire. Of them, 157 were excluded.
PARTICIPANTS AND METHODS: Seven hundred and six women, among whom 32% have
attained 40 years of age, were included in this study. A Cox regression model was
used to determine risk factors influencing the age at menopause. MAIN RESULTS:
Ninety seven women have reached menopause at a median age of 44 years. Menopause
has been surgically induced in 36% of women. In multivariate analysis, risk
factors for non-surgical menopause included exposure to alkylating agents,
increasing radiation dose to the ovaries, procarbazine dose, cyclophosphamide
dose and unilateral oophorectomy. The highest risk ratio for non-surgical
menopause was observed for women treated after the onset of puberty with
alkylating agents, either alone (RR = 9, 95% CI: 2.7-28, P = 0.0003) or
associated with even a low dose of radiation to the ovaries (RR = 29, 95% CI: 8
108, P < 0.0001). Exposure to unilateral oophorectomy is associated with a 7-year
earlier age at menopause. By the age of 40, only 2.1% had non-surgical premature
menopause and its main risk factors were age at diagnosis, cyclophosphamide dose,
exposure to melphalan and radiation dose to the ovaries. LIMITATIONS: The
information on menopause was based on self-reported data without confirmation by
FSH levels. Participants to this study have been treated for cancer from 1945 to
1985 and one can expect an increase in premature menopause incidence with more
recent protocols using high-dose alkylating agents. WIDER IMPLICATIONS OF THE
FINDINGS: This study provides data on risk factors for a reduced fertility window
in order to inform survivors at risk and help oncologists to design new
therapeutic protocols avoiding this risk. This study does not confirm the high
rate of premature menopause reported by the Childhood Cancer Survivor Study, but
this population differs from theirs (no leukemia and a lower percentage of
lymphoma).
PMID- 23154068
TI - The association of CGG repeats in the FMR1 gene and timing of natural menopause.
AB - STUDY QUESTION: Is there an association between the number of CGG repeats in the
FMR1 gene in the normal and intermediate range and age at natural menopause?
SUMMARY ANSWER: The number of CGG repeats in the normal and intermediate range in
the FMR1 gene was not associated with age at natural menopause. WHAT IS KNOWN
ALREADY: Excessive triple CGG repeats in the FMR1 gene have been widely
associated with primary ovarian insufficiency. Recently, the number of CGG
repeats in the normal and intermediate range (up to 55 repeats) was found to be
associated with serum levels of anti-Mullerian hormone and follicle-stimulating
hormone, as markers for ovarian ageing. This suggests that repeats in the normal
and intermediate range could be involved in the rate of exhaustion of the ovarian
primordial follicle pool and ultimately the timing of menopause. STUDY DESIGN,
SIZE: Cross-sectional study in a population-based sample of 3611 Caucasian women
with natural menopause. PARTICIPANTS/MATERIALS, SETTING, METHODS: The FMR1 CGG
repeat number was determined by PCR amplification in 3611 women with a known age
at natural menopause. A possible relation between CGG repeats in the normal and
intermediate range (up to 55 repeats) and menopausal age were analysed in various
ways, including linear regression analysis and analysis of variance. MAIN RESULTS
AND THE ROLE OF CHANCE: The number of CGG repeats in the normal and intermediate
range in the FMR1 gene was not associated with age at natural menopause. The mean
age at menopause was 50.30 (+/- 4.2) years for women with <45 repeats and 50.64
(+/- 3.4) years for women with intermediate-sized repeats (P = 0.37). Linear
regression analysis of the number of CGG repeats showed no association with
menopausal age (beta = 0.019, P = 0.16). LIMITATIONS, REASONS FOR CAUTION: In our
cohort, age at menopause was self-reported and determined retrospectively. WIDER
IMPLICATIONS OF THE FINDINGS: Earlier observations suggesting that the number of
CGG repeats in the normal and intermediate range is associated with the
individual variation of the ovarian ageing process could not be confirmed in the
current, large sample size study. A relation between the number of CGG repeats in
the normal and intermediate range and age at natural menopause appeared to be
absent. This finding questions the role of CGG repeat sizes in the ovarian ageing
process.
PMID- 23154069
TI - Hypoxia and lost gills: respiratory ecology of a temperate larval damselfly.
AB - Damselfly larvae, important predators and prey in many freshwater communities,
may be particularly sensitive to hypoxia because their caudal lamellae (external
gills) are frequently lost. In this study, we address how lost lamellae interact
with low oxygen to affect respiration and behavior of the widespread North
American damselfly Ischnura posita. Results showed no effect of lost lamellae on
resting metabolic rate or critical oxygen tension. Ventilation behaviors
increased only when dissolved oxygen (DO) was at or below 25% saturation and
these behaviors were not affected by the number of lamellae. Use of the oxygen
rich surface layer occurred almost exclusively at the lowest dissolved oxygen
level tested (10% saturation, 2.0 kPa). Damselflies that were missing lamellae
spent more time at the surface than individuals with intact lamellae. The
negative relationship between body size and time at the surface, and the negative
relationship between body mass and critical oxygen tension suggest that larger I.
posita may be more hypoxia tolerant than smaller individuals. Overall, I. posita
was minimally affected by missing lamellae and seems well-adapted to low DO
habitats. Average critical oxygen tension was very low (0.48 kPa, 2.4%
saturation), suggesting that individuals can maintain their metabolic rate across
a broad range of DO, and behaviors changed only at DO levels below the hypoxia
tolerance thresholds of many other aquatic organisms.
PMID- 23154070
TI - Intervertebral disc degeneration in the dog. Part 2: chondrodystrophic and non
chondrodystrophic breeds.
AB - Dogs can be grouped into two distinct types of breed based on the predisposition
to chondrodystrophy, namely, non-chondrodystrophic (NCD) and chondrodystrophic
(CD). In addition to a different process of endochondral ossification, NCD and CD
breeds have different characteristics of intravertebral disc (IVD) degeneration
and IVD degenerative diseases. The anatomy, physiology, histopathology, and
biochemical and biomechanical characteristics of the healthy and degenerated IVD
are discussed in the first part of this two-part review. This second part
describes the similarities and differences in the histopathological and
biochemical characteristics of IVD degeneration in CD and NCD canine breeds and
discusses relevant aetiological factors of IVD degeneration.
PMID- 23154071
TI - Survival of Mycoplasma agalactiae and Mycoplasma mycoides subspecies capri in
heat treated goat colostrum.
AB - The viability of Mycoplasma agalactiae and Mycoplasma mycoides subsp. capri (Mmc)
was assessed in goat colostrum treated at different temperatures. Samples of
colostrum were inoculated with reference strains of M. agalactiae (PG2) and Mmc
(PG3) and heated at 56 degrees C or 60 degrees C for 0, 30, 60, 90 or 120 min.
Viable colonies of M. agalactiae were recovered after all treatments and there
was a significant reduction in the concentration of viable M. agalactiae after 30
min at 56 degrees C and 60 degrees C. No viable colonies of Mmc were observed
after 60 min at 60 degrees C.
PMID- 23154073
TI - Frequency-dependent entrainment of neocortical slow oscillation to repeated
optogenetic stimulation in the anesthetized rat.
AB - Local field potential (LFP) slow oscillation (<1Hz) is typically observed in the
cortex during sleep or while under anesthesia and reflects synchronous
activation/inactivation of the cortical neuron population. The oscillation can be
entrained to repeated external sensory stimuli. To better understand the neural
mechanism underlying slow-oscillation generation and its entrainment to external
stimuli, we delivered optical stimulation to the cortex of anesthetized rats that
exogenously expressed the light-sensitive cation channel channelrhodopsin-2
(ChR2) and simultaneously monitored LFPs across cortical layers. We found that
the LFPs could be effectively entrained to repeated optical stimulation at 1Hz in
deep layers. A stimulus-triggered current-source density (CSD) analysis showed
that the evoked oscillation had the same depth and temporal profile as the slow
oscillations, indicating that both oscillations have the same neural mechanism.
Optical stimulation primarily induced the transition from the cortical up to down
state. These results suggest that the anesthetized rat cortex has an intrinsic
mechanism that leads to oscillation near 1Hz; effective entrainment to the 1Hz
stimulation reflects the resonated state of the cortex to that stimulus. Our
study is the first to demonstrate optogenetic manipulation of cortical slow
oscillation and provides a mechanistic explanation for slow-oscillation
entrainment.
PMID- 23154072
TI - In vitro and in vivo pharmacological profile of PL-3994, a novel cyclic peptide
(Hept-cyclo(Cys-His-Phe-d-Ala-Gly-Arg-d-Nle-Asp-Arg-Ile-Ser-Cys)-Tyr-[Arg
mimetic]-NH(2)) natriuretic peptide receptor-A agonist that is resistant to
neutral endopeptidase and acts as a bronchodilator.
AB - The pharmacological and airways relaxant profiles of PL-3994 (Hept-cyclo(Cys-His
Phe-d-Ala-Gly-Arg-d-Nle-Asp-Arg-Ile-Ser-Cys)-Tyr-[Arg mimetic]-NH(2)), a novel
natriuretic peptide receptor-A (NPR-A) agonist, were evaluated. PL-3994, a full
agonist, has high affinity for recombinant human (h), dog, or rat NPR-As (K(i)s
of 1, 41, and 10 nm, respectively), and produced concentration-dependent cGMP
generation in human, dog and rat NPR-As (respective EC(50)s of 2, 3 and 14 nm).
PL-3994 has a K(i) of 7 nm for hNPR-C but was without effect on cGMP generation
in hNPR-B. PL-3994 (1 MUm) was without significant effect against 75 diverse
molecular targets. PL-3994 or BNP, a natural NPR ligand, produced concentration
dependent relaxation of pre-contracted guinea-pig trachea (IC(50)s of 42.7 and
10.7 nm, respectively). PL-3994, and also BNP, (0.1 nm-100 MUm) elicited a
potent, concentration-dependent but small relaxation of pre-contracted human
precision-cut lung slices (hPCLS). Intratracheal PL-3994 (1-1000 MUg/kg) produced
a dose-dependent inhibition of the bronchoconstrictor response evoked by
aerosolized methacholine, but was without significant effect on cardiovascular
parameters. PL-3994 was resistant to degradation by human neutral endopeptidase
(hNEP) (92% remaining after 2 h), whereas the natural ligands, ANP and CNP, were
rapidly metabolized (<=1% remaining after 2 h). PL-3994 is a potent, selective
NPR agonist, resistant to NEP, with relaxant effects in guinea-pig and human
airway smooth muscle systems. PL-3994 has the profile predictive of longer
clinical bronchodilator activity than observed previously with ANP, and suggests
its potential utility in the treatment of asthma, in addition to being a useful
research tool to evaluate NPR biology.
PMID- 23154074
TI - Electrophysiological monitoring in patients with tumors of the skull base treated
by carbon-12 radiation therapy.
AB - PURPOSE: To report the results of short-term electrophysiologic monitoring of
patients undergoing (12)C therapy for the treatment of skull chordomas and
chondrosarcomas unsuitable for radical surgery. METHODS AND MATERIALS:
Conventional electroencephalogram (EEG) and retinal and cortical
electrophysiologic responses to contrast stimuli were recorded from 30 patients
undergoing carbon ion radiation therapy, within a few hours before the first
treatment and after completion of therapy. Methodologies and procedures were
compliant with the guidelines of the International Federation for Clinical
Neurophysiology and International Society for Clinical Electrophysiology of
Vision. RESULTS: At baseline, clinical signs were reported in 56.6% of subjects.
Electrophysiologic test results were abnormal in 76.7% (EEG), 78.6% (cortical
evoked potentials), and 92.8% (electroretinogram) of cases, without correlation
with neurologic signs, tumor location, or therapy plan. Results on EEG, but not
electroretinograms and cortical responses, were more often abnormal in patients
with reported clinical signs. Abnormal EEG results and retinal/cortical responses
improved after therapy in 40% (EEG), 62.5% (cortical potentials), and 70%
(electroretinogram) of cases. Results on EEG worsened after therapy in one-third
of patients whose recordings were normal at baseline. CONCLUSIONS: The
percentages of subjects whose EEG results improved or worsened after therapy and
the improvement of retinal/cortical responses in the majority of patients are
indicative of a limited or negligible (and possibly transient) acute central
nervous system toxicity of carbon ion therapy, with a significant beneficial
effect on the visual pathways. Research on large samples would validate
electrophysiologic procedures as a possible independent test for central nervous
system toxicity and allow investigation of the correlation with clinical signs;
repeated testing over time after therapy would demonstrate, and may help predict,
possible late toxicity.
PMID- 23154076
TI - 4pi non-coplanar liver SBRT: a novel delivery technique.
AB - PURPOSE: To improve the quality of liver stereotactic body radiation therapy
(SBRT) treatments, a novel 4pi framework was developed with accompanying
algorithms to optimize non-coplanar beam orientations and fluences. The dose
optimization is performed on a patient-specific deliverable beam geometry
solution space, parameterized with patient and linear accelerator gantry
orientations. METHODS AND MATERIALS: Beams causing collision between the gantry
and the couch or patient were eliminated by simulating all beam orientations
using a precise computer assisted design model of the linear accelerator and a
human subject. Integrated beam orientation and fluence map optimizations were
performed on remaining beams using a greedy column generation method. Testing of
the new method was performed on 10 liver SBRT cases previously treated with 50 to
60 Gy in 5 fractions using volumetric modulated arc therapy (VMAT). For each
patient, both 14 and 22 non-coplanar fields were selected and optimized to meet
the objective of >=95% of the planning target volume (PTV) covered by 100% of the
prescription dose. Doses to organs at risk, normal liver volumes receiving <15
Gy, integral dose, and 50% dose spillage volumes were compared against the
delivered clinical VMAT plans. RESULTS: Compared with the VMAT plans, the 4pi
plans yielded reduced 50% dose spillage volume and integral dose by 22% (range
10%-40%) and 19% (range 13%-26%), respectively. The mean normal liver volume
receiving <15 Gy was increased by 51 cc (range 21-107 cc) with a 31% reduction of
the mean normal liver dose. Mean doses to the left kidney and right kidney and
maximum doses to the stomach and spinal cord were on average reduced by 70%, 51%,
67%, and 64% (P<=.05). CONCLUSIONS: This novel 4pi non-coplanar radiation
delivery technique significantly improved dose gradient, reduced high dose
spillage, and improved organ at risk sparing compared with state of the art VMAT
plans.
PMID- 23154077
TI - Lack of a dose-effect relationship for pulmonary function changes after
stereotactic body radiation therapy for early-stage non-small cell lung cancer.
AB - PURPOSE: To evaluate the influence of tumor size, prescription dose, and dose to
the lungs on posttreatment pulmonary function test (PFT) changes after
stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung
cancer (NSCLC). METHODS AND MATERIALS: The analysis is based on 191 patients
treated at 5 international institutions: inclusion criteria were availability of
pre- and post-SBRT PFTs and dose-volume histograms of the lung and planning
target volume (PTV); patients treated with more than 1 SBRT course were excluded.
Correlation between early (1-6 months, median 3 months) and late (7-24 months,
median 12 months) PFT changes and tumor size, planning target volume (PTV) dose,
and lung doses was assessed using linear regression analysis, receiver operating
characteristics analysis, and Lyman's normal tissue complication probability
model. The PTV doses were converted to biologically effective doses and lung
doses to 2 Gy equivalent doses before correlation analyses. RESULTS: Up to 6
months after SBRT, forced expiratory volume in 1 second and carbon monoxide
diffusion capacity changed by -1.4% (95% confidence interval [CI], -3.4% to 0)
and -7.6% (95% CI, -10.2% to -3.4%) compared with pretreatment values,
respectively. A modest decrease in PFTs was observed 7-24 months after SBRT, with
changes of -8.1% (95% CI, -13.3% to -5.3%) and -12.4% (95% CI, -15.5% to -6.9%),
respectively. Using linear regression analysis, receiver operating characteristic
analysis, and normal tissue complication probability modeling, all evaluated
parameters of tumor size, PTV dose, mean lung dose, and absolute and relative
volumes of the lung exposed to minimum doses of 5-70 Gy were not correlated with
early and late PFT changes. Subgroup analysis based on pre-SBRT PFTs (greater or
equal and less than median) did not identify any dose-effect relationship.
CONCLUSIONS: This study failed to demonstrate a significant dose-effect
relationship for changes of pulmonary function after SBRT for early-stage non
small cell lung cancer.
PMID- 23154075
TI - RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation
therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of
acute morbidity in carcinoma of the anal canal.
AB - PURPOSE: A multi-institutional phase 2 trial assessed the utility of dose-painted
intensity modulated radiation therapy (DP-IMRT) in reducing grade 2+ combined
acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil
(5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15%
compared with the conventional radiation/5FU/MMC arm from RTOG 9811. METHODS AND
MATERIALS: T2-4N0-3M0 anal cancer patients received 5FU and MMC on days 1 and 29
of DP-IMRT, prescribed per stage: T2N0, 42 Gy elective nodal and 50.4 Gy anal
tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3, 45 Gy elective
nodal, 50.4 Gy <= 3 cm or 54 Gy >3 cm metastatic nodal and 54 Gy anal tumor PTVs
in 30 fractions. The primary endpoint is described above. Planned secondary
endpoints assessed all AEs and the investigator's ability to perform DP-IMRT.
RESULTS: Of 63 accrued patients, 52 were evaluable. Tumor stage included 54% II,
25% IIIA, and 21% IIIB. In primary endpoint analysis, 77% experienced grade 2+
gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a
significant reduction in acute grade 2+ hematologic, 73% (9811 85%, P=.032),
grade 3+ gastrointestinal, 21% (9811 36%, P=.0082), and grade 3+ dermatologic AEs
23% (9811 49%, P<.0001) with DP-IMRT. On initial pretreatment review, 81%
required DP-IMRT replanning, and final review revealed only 3 cases with normal
tissue major deviations. CONCLUSIONS: Although the primary endpoint was not met,
DP-IMRT was associated with significant sparing of acute grade 2+ hematologic and
grade 3+ dermatologic and gastrointestinal toxicity. Although DP-IMRT proved
feasible, the high pretreatment planning revision rate emphasizes the importance
of real-time radiation quality assurance for IMRT trials.
PMID- 23154078
TI - ATM polymorphisms predict severe radiation pneumonitis in patients with non-small
cell lung cancer treated with definitive radiation therapy.
AB - PURPOSE: The ataxia telangiectasia mutated (ATM) gene mediates detection and
repair of DNA damage. We investigated associations between ATM polymorphisms and
severe radiation-induced pneumonitis (RP). METHODS AND MATERIALS: We genotyped 3
potentially functional single nucleotide polymorphisms (SNPs) of ATM (rs1801516
[D1853N/5557G>A], rs189037 [-111G>A] and rs228590) in 362 patients with non-small
cell lung cancer (NSCLC), who received definitive (chemo)radiation therapy. The
cumulative severe RP probabilities by genotypes were evaluated using the Kaplan
Meier analysis. The associations between severe RP risk and genotypes were
assessed by both logistic regression analysis and Cox proportional hazard model
with time to event considered. RESULTS: Of 362 patients (72.4% of non-Hispanic
whites), 56 (15.5%) experienced grade >=3 RP. Patients carrying ATM rs189037
AG/GG or rs228590 TT/CT genotypes or rs189037G/rs228590T/rs1801516G (G-T-G)
haplotype had a lower risk of severe RP (rs189037: GG/AG vs AA, adjusted hazard
ratio [HR] = 0.49, 95% confidence interval [CI], 0.29-0.83, P=.009; rs228590:
TT/CT vs CC, HR=0.57, 95% CI, 0.33-0.97, P=.036; haplotype: G-T-G vs A-C-G,
HR=0.52, 95% CI, 0.35-0.79, P=.002). Such positive findings remained in non
Hispanic whites. CONCLUSIONS: ATM polymorphisms may serve as biomarkers for
susceptibility to severe RP in non-Hispanic whites. Large prospective studies are
required to confirm our findings.
PMID- 23154079
TI - The interaction of nemorubicin metabolite PNU-159682 with DNA fragments
d(CGTACG)(2), d(CGATCG)(2) and d(CGCGCG)(2) shows a strong but reversible binding
to G:C base pairs.
AB - The antitumor anthracycline nemorubicin is converted by human liver microsomes to
a major metabolite, PNU-159682 (PNU), which was found to be much more potent than
its parent drug toward cultured tumor cells and in vivo tumor models. The
mechanism of action of nemorubicin appears different from other anthracyclines
and until now is the object of studies. In fact PNU is deemed to play a dominant,
but still unclear, role in the in vivo antitumor activity of nemorubicin. The
interaction of PNU with the oligonucleotides d(CGTACG)(2), d(CGATCG)(2) and
d(CGCGCG)(2) was studied with a combined use of (1)H and (31)P NMR spectroscopy
and by ESI-mass experiments. The NMR studies allowed to establish that the
intercalation between the base pairs of the duplex leads to very stable complexes
and at the same time to exclude the formation of covalent bonds. Melting
experiments monitored by NMR, allowed to observe with high accuracy the behaviour
of the imine protons with temperature, and the results showed that the re
annealing occurs after melting. The formation of reversible complexes was
confirmed by HPLC-tandem mass spectra, also combined with endonuclease
P1digestion. The MS/MS spectra showed the loss of neutral PNU before breaking the
double helix, a behaviour typical of intercalators. After digestion with the
enzyme, the spectra did not show any compound with PNU bound to the bases. The
evidence of a reversible process appears from both proton and phosphorus NOESY
spectra of PNU bound to d(CGTACG)(2) and to d(CGATCG)(2). The dissociation rate
constants (k(off)) of the slow step of the intercalation process, measured by
(31)P NMR NOE-exchange experiments, showed that the kinetics of the process is
slower for PNU than for doxorubicin and nemorubicin, leading to a 10- to 20-fold
increase of the residence time of PNU into the intercalation sites, with respect
to doxorubicin. A relevant number of NOE interactions allowed to derive a model
of the complexes in solution from restrained MD calculations. The conformation of
PNU bound to the oligonucleotides was also derived from the coupling constant
values.
PMID- 23154080
TI - Environmental factors and their regulation of immunity in multiple sclerosis.
AB - Epidemiological and clinical studies have shown that environmental factors such
as infections, smoking and vitamin D are associated with the risk of developing
multiple sclerosis (MS). Some of these factors also play a role in the MS disease
course. We are currently beginning to understand how environmental factors may
impact immune function in MS on a cellular and molecular level. Here we review
epidemiological, clinical and basic immunological studies on the environmental
factors, viral and parasitic infections, smoking, and vitamin D and relate
epidemiological findings with their likely pathophysiology in MS.
PMID- 23154081
TI - Anaphylaxis from ingestion of mites: pancake anaphylaxis.
AB - Oral mite anaphylaxis is a new syndrome characterized by severe allergic symptoms
occurring immediately after eating foods made with mite-contaminated wheat flour.
This syndrome, which is more prevalent in tropical environments, is triggered
more often by pancakes, and for that reason, it has been designated "the pancake
syndrome." Because cooked foods are able to induce the symptoms, it has been
suggested that thermoresistant allergens are involved in its pathogenesis. A
variety of this syndrome can occur during physical exercise (dust mite ingestion
associated exercise-induced anaphylaxis).
PMID- 23154083
TI - Induction of severe systemic lupus erythematosus by TNF blockade and response to
anti-IL-6 strategy.
PMID- 23154082
TI - Obesity impairs apoptotic cell clearance in asthma.
AB - BACKGROUND: Asthma in obese adults is typically more severe and less responsive
to glucocorticoids than asthma in nonobese adults. OBJECTIVE: We sought to
determine whether the clearance of apoptotic inflammatory cells (efferocytosis)
by airway macrophages was associated with altered inflammation and reduced
glucocorticoid sensitivity in obese asthmatic patients. METHODS: We investigated
the relationship of efferocytosis by airway (induced sputum) macrophages and
blood monocytes to markers of monocyte programming, in vitro glucocorticoid
response, and systemic oxidative stress in a cohort of adults with persistent
asthma. RESULTS: Efferocytosis by airway macrophages was assessed in obese (n=14)
and nonobese (n=19) asthmatic patients. Efferocytosis by macrophages was 40%
lower in obese than nonobese subjects, with a mean efferocytic index of 1.77 (SD,
1.07) versus 3.00 (SD, 1.25; P<.01). A similar reduction of efferocytic function
was observed in blood monocytes of obese participants. In these monocytes there
was also a relative decrease in expression of markers of alternative (M2)
programming associated with efferocytosis, including peroxisome proliferator
activated receptor delta and CX3 chemokine receptor 1. Macrophage efferocytic
index was significantly correlated with dexamethasone-induced mitogen-activated
protein kinase phosphatase 1 expression (rho=0.46, P<.02) and baseline
glucocorticoid receptor alpha expression (rho=0.44, P<.02) in PBMCs. Plasma 4
hydroxynonenal levels were increased in obese asthmatic patients at 0.33 ng/mL
(SD, 0.15 ng/mL) versus 0.16 ng/mL (SD, 0.08 ng/mL) in nonobese patients (P=.006)
and was inversely correlated with macrophage efferocytic index (rho=-0.67,
P=.02). CONCLUSIONS: Asthma in obese adults is associated with impaired
macrophage/monocyte efferocytosis. Impairment of this anti-inflammatory process
is associated with altered monocyte/macrophage programming, reduced
glucocorticoid responsiveness, and systemic oxidative stress.
PMID- 23154086
TI - Molecular pathways: regulation of metabolism by RB.
AB - The discovery of the retinoblastoma (RB-1) gene as a tumor suppressor that is
disrupted in a majority of human cancers either via direct or indirect genetic
alterations has resulted in increased interest in its functions and downstream
effectors. Although the canonical pathway that links this tumor suppressor to
human cancers details its interaction with the E2F transcription factors and cell
cycle progression, recent studies have shown an essential role for RB-1 in the
suppression of glycolytic and glutaminolytic metabolism. Characterization of the
precise metabolic transporters and enzymes suppressed by the RB-E2F axis should
enable the identification of small molecule antagonists that have selective and
potent antitumor properties.
PMID- 23154084
TI - Examination of the relationship between variation at 17q21 and childhood wheeze
phenotypes.
AB - BACKGROUND: Genome-wide association studies have identified associations of
genetic variants at 17q21 near ORMDL3 with childhood asthma. OBJECTIVES: We
sought to determine whether associations in this region are specific to
particular asthma phenotypes and specific to ORMDL3. METHODS: We examined
associations between 244 independent single nucleotide polymorphisms (SNPs) plus
13 previously identified asthma-related SNPs in the region between 34 and 36 Mb
on chromosome 17 and early wheezing phenotypes, doctor-diagnosed asthma and atopy
at 71/2 years, and bronchial hyperresponsiveness and lung function at 81/2 years
in 7045 children from the Avon Longitudinal Study of Parents and Children birth
cohort study. With this, cis expression quantitative trait loci signals for the
same SNPs were assessed in 875 samples across genes in the same region. RESULTS:
The strongest evidence for phenotypic association was seen for persistent
wheezing (rs8076131 near ORMDL3: relative risk ratio [RRR], 1.60 [95% CI, 1.40
1.84], P = 1.4 * 10(-11); rs2305480 near GSDML: RRR, 1.60 [95% CI, 1.39-1.83], P
= 1.5 * 10(-11); and rs9303277 near IKZF3: RRR, 1.57 [95% CI, 1.37-1.79], P = 4.4
* 10(-11)). Similar but less precisely estimated effects were seen for
intermediate-onset wheeze, but there was little evidence of associations with
other wheezing phenotypes. There was some evidence of associations with bronchial
hyperresponsiveness. SNPs across the whole region show strong evidence of
association with differential levels of expression at GSDML, IKZF3, and MED24, as
well as ORMDL3. CONCLUSIONS: Associations of SNPs in the 17q21 locus are specific
to asthma and specific wheezing phenotypes and are not explained by associations
with intermediate phenotypes, such as atopy or lung function.
PMID- 23154087
TI - Epidemiological analysis of a cluster within the outbreak of Shiga toxin
producing Escherichia coli serotype O104:H4 in Northern Germany, 2011.
AB - In May 2011 one of the worldwide largest outbreaks of haemolytic uraemic syndrome
(HUS) and bloody diarrhoea caused by Shiga toxin-producing Escherichia coli
(STEC) serotype O104:H4 occurred in Germany. One of the most affected federal
states was Lower Saxony. We present the investigation of a cluster of STEC and
HUS cases within this outbreak by means of a retrospective cohort study. After a
70th birthday celebration which took place on 7th of May 2011 among 72 attendants
seven confirmed cases and four probable cases were identified, two of them
developed HUS. Median incubation period was 10 days. Only 35 persons (48.6%)
definitely answered the question whether they had eaten the sprouts that were
used for garnishing the salad. Univariable analysis revealed different food
items, depending on the case definition, with Odds Ratio (OR)>1 indicating an
association with STEC infection, but multivariable logistic regression showed no
increased risk for STEC infection for any food item and any case definition.
Sprouts as the source for the infection had to be assumed based on the results of
a tracing back of the delivery ways from the catering company to the sprouts
producer who was finally identified as the source of the entire German outbreak.
In this large outbreak several case-control studies failed to identify the source
of infection.
PMID- 23154088
TI - Renewed efforts are needed to curb antibiotic resistance.
PMID- 23154089
TI - Family of patient who died during a clinical trial receive a six figure
settlement.
PMID- 23154090
TI - Status of women is central to reducing child mortality in India, report says.
PMID- 23154091
TI - Common mechanisms of auditory hallucinations-perfusion studies in epilepsy.
AB - Auditory hallucinations (AH) occur in various neurological and psychiatric
disorders. In psychosis, increased neuronal activity in the primary auditory
cortex (PAC) contributes to AH. We investigated functional neuroanatomy of
epileptic hallucinations by measuring cerebral perfusion in three patients with
AH during simple partial status epilepticus. Hyperperfusion in the temporal lobe
covering the PAC occurred in all patients. Our perfusion data support the
hypothesis of PAC being a constituting element in the genesis of AH independent
of their aetiology.
PMID- 23154092
TI - Frontoparietal attentional network activation differs between smokers and
nonsmokers during affective cognition.
AB - Smoking withdrawal-induced disruption of affect and cognition is associated with
dysregulated prefrontal brain function, although little is known regarding the
neural foci of smoker-nonsmoker differences during affective cognition. Thus, the
current study used functional magnetic resonance imaging (fMRI) to identify
smoker-nonsmoker differences in affective cognition. Thirty-four healthy
volunteers (17 smokers, 17 nonsmokers) underwent fMRI during an affective Stroop
task (aST). The aST includes emotional cue-reactivity trials, and response
selection trials that contain either neutral or negative emotional distractors.
Smokers had less activation during negative cue-reactivity trials in regions
subserving emotional awareness (i.e., posterior cingulate), inhibitory control
(i.e., inferior frontal gyrus) and conflict resolution (i.e., anterior
cingulate); during response-selection trials with negative emotional distractors,
smokers had greater activation in a frontoparietal attentional network (i.e.,
middle frontal and supramarginal gyri). Exploratory analyses revealed that task
accuracy was positively correlated with anterior cingulate cortex and inferior
frontal gyrus response on fMRI. These findings suggests that chronic nicotine use
may reduce inhibitory control and conflict resolution of emotional distraction,
and result in recruiting additional attentional resources during emotional
interference on cognition.
PMID- 23154094
TI - Abnormal neural activity in partially remitted late-onset depression: an fMRI
study of one-back working memory task.
AB - Only half of the geriatric patients with major depressive disorder (MDD) can
reach full remission after treatment of half a year. This study was designed to
examine the neural responses in the partial responders of late-onset MDD. We used
3-Tesla functional magnetic resonance imaging to assess the patterns of cerebral
activation/deactivation in the performance of a one-back version of the n-back
working memory task. We recruited 14 major depressive patients who reached
partial remission after at least half a year of pharmacological intervention,
compared with 14 non-depressive controls. There were no significant between-group
differences in the demographical profiles and working memory performance, which
was true for both accuracy and reaction time. Brain masks encompassing the neural
responses of activation/deactivation were constructed from the non-depressive
controls. The depressive group shows enhanced activities at left middle frontal
and left parietal regions, and reduced deactivation at several temporal regions
and left amygdala within the masks. Besides, the depressive group activates extra
neural nodes at middle frontal and middle temporal regions outside the masks. The
neural responses in the left amygdala are significantly correlated with the
severity of depression and comorbid anxiety. The loss of deactivation in the left
amygdala and the temporal areas in cognitive endeavor may be related to the
refractoriness to treatment.
PMID- 23154093
TI - Neurometabolite concentration and clinical features of chronic alcohol use: a
proton magnetic resonance spectroscopy study.
AB - Chronic, heavy alcohol consumption may affect the concentration of
neurometabolites assessed with proton magnetic resonance spectroscopy ((1)H-MRS).
We investigated the largest sample reported to date (N=213) with the primary goal
of determining how specific clinical features impact neurometabolite
concentrations in an anterior cingulate gray matter voxel. This community
dwelling sample included both treatment-seeking and non-treatment-seeking
individuals. A healthy control group (N=66) was matched for age and education. In
multivariate analyses predicting neurometabolite concentrations, the heavy
drinking group had greater concentrations overall. An age by group interaction
was noted, as group difference across neurometabolites increased with age. More
years drinking, but not more drinks per drinking day (DPDD), predicted greater
concentrations of choline-containing compounds (Cho), creatine-phosphocreatine
(Cre), glutamate-glutamine (Glx), and N-acetyl-aspartate (NAA). The effects of
other clinical variables (depression, cigarette smoking, marijuana use) were
negligible. After controlling for DPDD and years drinking, treatment-seeking
status had no impact on neurometabolites. In the very oldest portion of the
sample (mean age=50), however, a negative relationship was seen between NAA and
years drinking. These results suggest that the nature of neurometabolite
abnormalities in chronic heavy drinkers may vary as a function of duration of
abuse.
PMID- 23154095
TI - Recent binge drinking predicts smaller cerebellar volumes in adolescents.
AB - The current study examined the effects of recent binge drinking on cerebellar
morphometry in a sample of healthy adolescents. Participants were 106 teenagers
(46 bingers and 60 controls) aged 16-19 who received a high-resolution magnetic
resonance imaging (MRI) scan. FreeSurfer segmented and quantified the volume of
each cerebellum. Maximum drinks during a binge in the past 3 months and duration
since last binge were examined as predictors of cerebellar volume, after
controlling for potentially confounding variables. In the 106 teens, higher peak
drinks predicted smaller left hemisphere cerebellar gray and whitematter, and
right hemisphere cerebellar gray matter, and marginally predicted smaller right
hemisphere cerebellar white matter. Gender did not moderate these effects. More
intense adolescent binge drinking is linked to smaller cerebellar volumes even in
healthy teens, above and beyond variability attributable to risk factors for
binge drinking. Longitudinal research is needed to see if cerebellar volumes
worsen with protracted drinking and recover with abstinence. Interventions aimed
at improving brain structure in adolescent binge drinkers are necessary given the
high prevalence of risky drinking in youth.
PMID- 23154096
TI - Absence of anatomic corpus callosal abnormalities in childhood-onset
schizophrenia patients and healthy siblings.
AB - The corpus callosum (CC) has been implicated in the pathogenesis of
schizophrenia, and CC deficits have been reported in adults with schizophrenia.
We explored the developmental trajectory of the corpus callosum in childhood
onset schizophrenia (COS) patients, their healthy siblings (SIB) and healthy
volunteers. We obtained 235 anatomic brain magnetic resonance imaging (MRI) scans
from 98 COS patients, 153 scans from 71 of their healthy siblings, and 253 scans
from 100 age- and gender-matched healthy volunteers, across ages 9-30 years. The
volumes of five sub-regions of the CC were calculated using FreeSurfer, and
summed to give the total volume. Longitudinal data were examined using mixed
model regression analysis. There were no significant differences for the total or
sub-regional CC volumes between the three groups. There were also no significant
differences between the groups for developmental trajectory (slope) of the CC.
This is the largest longitudinal study of CC development in schizophrenia and the
first COS study of the CC to include healthy siblings. Overall, CC volume and
growth trajectory did not differ between COS patients, healthy siblings, or
healthy volunteers. These results suggest that CC development, at least at a
macroscopic level, may not be a salient feature of schizophrenia.
PMID- 23154097
TI - Silent brain infarcts: a cause of depression in the elderly?
AB - The present study included 1047 elderly participants. At baseline, brain magnetic
resonance imaging (MRI) was performed to detect infarcts and white matter
lesions; further, depressive disorders were assessed. Participants were followed
up during 3.6 years to determine incident and recurrent depression. We found an
increased risk of recurrent depression associated with silent brain infarcts.
PMID- 23154098
TI - Neural functional and structural correlates of childhood maltreatment in women
with intimate-partner violence-related posttraumatic stress disorder.
AB - Childhood maltreatment (CM) is a strong risk factor for development of
posttraumatic stress disorder (PTSD) upon adult exposure to extreme adverse
events. However, the neural underpinnings of this relationship are not well
understood. Here, we test the hypothesis that severity of CM history is
positively correlated with emotion-processing limbic and prefrontal brain
activation/connectivity and negatively correlated with prefrontal gray matter
volumes in women with PTSD due to intimate-partner violence (IPV-PTSD). Thirty
three women with IPV-PTSD underwent structural and functional magnetic resonance
imaging while completing a facial emotion processing task. Multivariate
regressions examined the relationship of CM to patterns of activation,
connectivity, and gray matter volumes. CM severity was: (a) positively correlated
with ventral ACC activation while processing angry faces; (b) negatively
correlated with dorsal ACC and insula activation while processing fear and angry
faces, arising from positive correlations with the shape-matching baseline; (c)
positively correlated with limbic-prefrontal connectivity while processing fear
faces but negatively correlated with amygdalo-insular connectivity while
processing fear and angry; and (d) negatively correlated with prefrontal gray
matter volumes. These results suggest CM exposure may account for variability in
limbic/prefrontal brain function and prefrontal structure in adulthood PTSD and
offer one potential mechanism through which CM confers risk to future development
of PTSD.
PMID- 23154099
TI - Glutamate system genes and brain volume alterations in pediatric obsessive
compulsive disorder: a preliminary study.
AB - Obsessive-compulsive disorder (OCD) has been associated with regional volumetric
brain abnormalities, which provide promising intermediate phenotypes of the
disorder. In this study, volumes of brain regions selected for a priori evidence
of association with OCD (orbitofrontal cortex (OFC), anterior cingulate cortex
(ACC), thalamus, caudate, putamen, globus pallidus and pituitary) were measured
using structural magnetic resonance imaging (MRI) in 20 psychotropic-naive
pediatric OCD patients. We examined the association between these regional brain
volumes and a total of 519 single nucleotide polymorphisms (SNPs) from nine
glutamatergic candidate genes (DLGAP1, DLGAP2, DLGAP3, GRIN2B, SLC1A1, GRIK2,
GRIK3, SLITRK1 and SLITRK5). These genes were selected based on either previous
reported association with OCD in humans or evidence from animal models of OCD.
After correcting for multiple comparisons by permutation testing, no SNP remained
significantly associated with volumetric changes. The strongest trend toward
association was identified between two SNPs in DLGAP2 (rs6558484 and rs7014992)
and OFC white matter volume. Our other top ranked association findings were with
ACC, OFC and thalamus. These preliminary results suggest that sequence variants
in glutamate candidate genes may be associated with structural neuroimaging
phenotypes of OCD.
PMID- 23154101
TI - [Reply to the letter "Comments on peritonsillar infections: a prospective study
of 100 consecutive cases"].
PMID- 23154100
TI - Interaction between serotonin transporter and dopamine D2/D3 receptor radioligand
measures is associated with harm avoidant symptoms in anorexia and bulimia
nervosa.
AB - Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) have alterations
of measures of serotonin (5-HT) and dopamine (DA) function, which persist after
long-term recovery and are associated with elevated harm avoidance (HA), a
measure of anxiety and behavioral inhibition. Based on theories that 5-HT is an
aversive motivational system that may oppose a DA-related appetitive system, we
explored interactions of positron emission tomography (PET) radioligand measures
that reflect portions of these systems. Twenty-seven individuals recovered (REC)
from eating disorders (EDs) (7 AN-BN, 11 AN, 9 BN) and nine control women (CW)
were analyzed for correlations between [(11)C]McN5652 and [(11)C]raclopride
binding. There was a significant positive correlation between [(11)C]McN5652
binding potential (BP(non displaceable(ND))) and [(11)C]Raclopride BP(ND) for the
dorsal caudate, antero-ventral striatum (AVS), middle caudate, and ventral and
dorsal putamen. No significant correlations were found in CW. [(11)C]Raclopride
BP(ND), but not [(11)C]McN5652 BP(ND), was significantly related to HA in REC
EDs. A linear regression analysis showed that the interaction between
[(11)C]McN5652 BP(ND) and [(11)C]raclopride BP(ND) in the dorsal putamen
significantly predicted HA. This is the first study using PET and the
radioligands [(11)C]McN5652 and [(11)C]raclopride to show a direct relationship
between 5-HT transporter and striatal DA D2/D3 receptor binding in humans,
supporting the possibility that 5-HT and DA interactions contribute to HA
behaviors in EDs.
PMID- 23154103
TI - d-Dimer and simplified pulmonary embolism severity index in relation to right
ventricular function.
AB - BACKGROUND: Right ventricular (RV) involvement in pulmonary embolism (PE) is an
ominous sign. The aim of this study was to investigate the extent to which the d
dimer level or simplified PE severity index (sPESI) indicates RV dysfunction in
patients with preserved systemic arterial pressure. METHODS: Right ventricular
function was studied in 34 consecutive patients with acute nonmassive PE by
echocardiography including Doppler tissue imaging within 24 hours after arrival
to the hospital. d-Dimer and sPESI were assessed upon arrival. RESULTS: d-Dimer
correlated with RV pressure (Rs, 0.60; P < .001) and pulmonary vascular
resistance (PVR; Rs, 0.68; P < .0001) and tended to be related to myocardial
performance index (MPI; Rs, 0.31; P = .067). Compared to a level less than 3.0
mg/L, patients with d-dimer 3.0 mg/L or higher had lower systolic tricuspid
annular velocity (11.3 +/- 2.7 vs 13.5 +/- 2.7 cm/s; P < .05), a prolonged MPI
(0.8 +/- 0.3 vs 0.5 +/- 0.2; P < .01), increased RV pressure (58 +/- 13 vs 37 +/-
12 mm Hg; P < .001), and increased PVR (3.3 +/- 1.1 vs 1.8 +/- 0.4 Woods units; P
< .001). Patients in the high-risk sPESI group had higher filling pressure than
those in the low risk sPESI group. CONCLUSIONS: In the acute stage of PE, a d
dimer level 3 mg/L or higher may identify nonmassive PE patients with RV
dysfunction and thereby help to determine their risk profile. We found no
additional value for sPESI in this context.
PMID- 23154102
TI - Cerebral regional oxygen saturation monitoring in pediatric malfunctioning shunt
patients.
AB - BACKGROUND: Shunt malfunction produces increased intracranial pressure causing
decreased cerebral regional perfusion and tissue O(2)sat. Cerebral regional
oxygen saturation (rSO(2)) by near-infrared spectroscopy represents tissue
perfusion and oxygen saturation. Cerebral rSO(2) is used to detect cerebral
ischemia in pediatric clinical settings. OBJECTIVE: The objective of the study
was to determine the reliability of cerebral rSO(2) in pediatric malfunctioning
shunt. METHODS: A prospective observational study of pediatric patients presented
to the pediatric emergency department was conducted. Confirmed malfunctioning
shunt subjects had cerebral rSO(2) monitoring. RESULTS: A total of 131
malfunctioning shunt subjects had cerebral rSO(2) monitoring. Patient's central
trend and intrasubject variability of cerebral rSO(2) readings for left and right
probe and malfunction sites (n = 131) are as follows: Intrasubject left and
right rSO(2) Pearson correlation was -0.46 to 0.98 (mean +/- SD, 0.35 +/- 0.34;
median, 0.34; interquartile range, 0.06-0.61). The correlation coefficients of 99
subjects between left and right rSO(2) was significantly different (P < .001),
suggesting that intrasubjects' left and right rSO(2) are highly correlated.
Sample mean difference between left and right rSO(2) were -1.7% (95% confidence
interval [CI], -1.8 to -1.6; P < .001) supporting overall left lower than right.
Intraclass correlation for left rSO(2) was 87.4% (95% CI, 87.2%-87.6%), and that
for right rSO(2) was 83.8% (95% CI, 83.8%-84%), showing intersubject differences
accounting for the variation, and relative to intersubject variation,
intrasubjects readings are consistent. Intrasubjects, left and right rSO(2)
highly correlate and are asymmetrical. Left and right rSO(2) are consistent in
intrasubject with large rSO(2) variations in trend and variability across
subjects. CONCLUSION: This study demonstrates reliable cerebral rSO(2) readings
in subjects with malfunctioning shunts, with asymmetrical cerebral rSO(2)
hemispheric dynamics within subjects.
PMID- 23154104
TI - Retrospective time series analysis of veterinary laboratory data: preparing a
historical baseline for cluster detection in syndromic surveillance.
AB - The practice of disease surveillance has shifted in the last two decades towards
the introduction of systems capable of early detection of disease. Modern
biosurveillance systems explore different sources of pre-diagnostic data, such as
patient's chief complaint upon emergency visit or laboratory test orders. These
sources of data can provide more rapid detection than traditional surveillance
based on case confirmation, but are less specific, and therefore their use poses
challenges related to the presence of background noise and unlabelled temporal
aberrations in historical data. The overall goal of this study was to carry out
retrospective analysis using three years of laboratory test submissions to the
Animal Health Laboratory in the province of Ontario, Canada, in order to prepare
the data for use in syndromic surveillance. Daily cases were grouped into
syndromes and counts for each syndrome were monitored on a daily basis when
medians were higher than one case per day, and weekly otherwise. Poisson
regression accounting for day-of-week and month was able to capture the day-of
week effect with minimal influence from temporal aberrations. Applying Poisson
regression in an iterative manner, that removed data points above the predicted
95th percentile of daily counts, allowed for the removal of these aberrations in
the absence of labelled outbreaks, while maintaining the day-of-week effect that
was present in the original data. This resulted in the construction of time
series that represent the baseline patterns over the past three years, free of
temporal aberrations. The final method was thus able to remove temporal
aberrations while keeping the original explainable effects in the data, did not
need a training period free of aberrations, had minimal adjustment to the
aberrations present in the raw data, and did not require labelled outbreaks.
Moreover, it was readily applicable to the weekly data by substituting Poisson
regression with moving 95th percentiles.
PMID- 23154105
TI - The impact of animal introductions during herd restrictions on future herd-level
bovine tuberculosis risk.
AB - In Ireland new cases of bovine tuberculosis (bTB) are detected using both field
(with the single intradermal comparative tuberculin test (SICTT)) and abattoir
surveillance. Once a new case has been detected, herd restrictions, including
restrictions on animal movements into and out of the herd, are implemented until
the herd has passed two consecutive clear tests. While a herd is restricted,
there may be several reasons why it may be desirable to introduce new stock, such
as enabling routine management practices to continue 'as near to normal'. In
Ireland, introduction of animals during a bTB episode is permitted under specific
conditions, with permission from the local veterinary office. The objectives of
this study were (1) to provide an overview of movement events associated with
each bTB episode, (2) to determine whether introduction of animals during a bTB
episode is associated with increased future bTB risk and (3) to identify the
practices relating to the introduction of animals that are the most risky. All
herds that were not restricted at the start of 2006, but experienced a bTB
episode during 2006 with 2 or more SICTT standard reactors (the eligible bTB
episode) were included in the study. We calculated the number of extended
eligible bTB episodes and subsequent bTB episodes that could be directly
attributed to introduced animals. The main outcome of interest was the time from
de-restriction of the eligible bTB episode to the start of a subsequent bTB
episode or the date of the last test prior to the end of the study (31 December
2010). Cox proportional-hazard models were developed, each using a different
introduction variable: introduced animals during an episode (yes/no), introduced
animals prior to the first retest/first clear test, time from start of episode
until first animals introduced and number of animals introduced during the
episode. Only a small proportion of subsequent bTB episodes (1.8%) or extended
eligible bTB episodes (2.7%) could be directly attributed to introduced animals.
The results highlight an increased risk of a subsequent bTB episode among only a
subset of herds that introduced animals during the eligible bTB episode.
Specifically, herds that introduced animals early during the eligible bTB episode
were at significantly greater future bTB risk than herds where animals were only
introduced later. To illustrate, herds that introduced animals after the first
retest did not have a significantly different risk compared to herds that did not
introduce animals at all. In contrast, herds that did introduce animals prior to
the first retest had 1.5 times higher risk of a subsequent bTB episode. Future
practices concerning the introduction of animals during an episode now need to be
reviewed.
PMID- 23154106
TI - Prospects for cost reductions from relaxing additional cross-border measures
related to livestock trade.
AB - Compared with the domestic trade in livestock, intra-communal trade across the
European Union (EU) is subject to costly, additional veterinary measures. Short
distance transportation just across a border requires more measures than long
distance domestic transportation, while the need for such additional cross-border
measures can be questioned. This study examined the prospects for cost reductions
from relaxing additional cross-border measures related to trade within the cross
border region of the Netherlands (NL) and Germany (GER); that is, North Rhine
Westphalia and Lower Saxony. The study constructed a deterministic spread-sheet
cost model to calculate the costs of both routine veterinary measures (standard
measures that apply to both domestic and cross-border transport) and additional
cross-border measures (extra measures that only apply to cross-border transport)
as applied in 2010. This model determined costs by stakeholder, region and
livestock sector, and studied the prospects for cost reduction by calculating the
costs after the relaxation of additional cross-border measures. The selection
criteria for relaxing these measures were (1) a low expected added value on
preventing contagious livestock diseases, (2) no expected additional veterinary
risks in case of relaxation of measures and (3) reasonable cost-saving
possibilities. The total cost of routine veterinary measures and additional cross
border measures for the cross-border region was ?22.1 million, 58% (?12.7
million) of which came from additional cross-border measures. Two-thirds of this
?12.7 million resulted from the trade in slaughter animals. The main cost items
were veterinary checks on animals (twice in the case of slaughter animals),
export certification and control of export documentation. Four additional cross
border measures met the selection criteria for relaxation. The relaxation of
these measures could save ?8.2 million (?5.0 million for NL and ?3.2 million for
GER) annually. Farmers would experience the greatest savings (99%), and most
savings resulted from relaxing additional cross-border measures related to
poultry (48%), mainly slaughter broilers (GER), and pigs (48%), mainly slaughter
pigs (NL). In particular, the trade in slaughter animals (dead-end hosts) is
subject to measures, such as veterinary checks on both sides of the border that
might not contribute to preventing contagious livestock diseases. Therefore, this
study concludes that there are several possibilities for reducing the costs of
additional cross-border measures in both countries.
PMID- 23154107
TI - Impact of demographic characteristics in pet ownership: modeling animal count
according to owners income and age.
AB - Pet owner characteristics such as age, gender, income/social class, marital
status, rural/urban residence and household type have been shown to be associated
with the number of owned pets. However, few studies to date have attempted to
evaluate these associations in Brazil. Accordingly, the aim of this study was to
evaluate the association between age and income of owners and the number of owned
dogs and cats in a Brazilian urban center. Pinhais, metropolitan area of
Curitiba, Southern Brazil, the seventh largest city in Brazil, was chosen for
this study. Questionnaires were administered door-to-door between January and
February 2007 and data were analyzed by zero-inflated negative binomial (ZINB)
models. A total of 13,555 of 30,380 (44.62%) households were interviewed. The
majority (62.43%) of households reported having one or more dogs, with one or two
dogs being the most common (29.97% and 19.71%, respectively). Cat ownership per
household was much lower (P=0.001) than dog ownership, with 90% of the households
reported having no owned cats. ZINB analyses indicated that income is not
associated with the number of both dogs and cats among households that have pets.
However, households from higher income categories were more likely to have dogs
(but not cats) when compared to the lowest income category (P<0.05),
contradicting a common belief that the poorer the family, the more likely they
have pets. Certain age categories were significantly associated with the number
of dogs or cats in households that have pets. In addition, most age categories
were significantly associated with having dogs and/or cats (P<0.05). In
conclusion, our study has found that age but not household income is associated
with the number of dogs or cats in households that have pets; higher income
households were more likely to have dogs when compared to low-income households.
PMID- 23154108
TI - [Facial edema].
PMID- 23154109
TI - [Standardized geriatric assessment or comprehensive gerontological assessment:
where do we stand?].
AB - The concept of comprehensive gerontological assessment is a foundation of modern
geriatrics. Our focus was to try to clarify the underlying concepts, assess the
level of evidence and clarify the issues still under debate. The concept implies
the definition of an interdisciplinary process for a multidimensional assessment
in order to produce a coordinated plan. The central notion is that the
systematization of this multidimensionality and interdisciplinarity needs the
establishment of dedicated process (meeting tools, clinical information system,
etc.). Following dimensions should be covered: health, social, economic,
environmental and psychological. Any assessment process that could lead to
forgetting one of its dimensions cannot be viewed as a comprehensive
gerontological assessment. The level of evidence is higher in hospital acute
inpatient unit but it is still low in all other areas of health care but the
scattered data in the literature argues for qualitative benefits (improved
quality of care or quality of life). The questions that remain are numerous
including the choice of strategy for initial evaluation (maximum versus minimum;
from the outset by many professionals versus graduated based on the minimum
initial evaluation), the choice of tool, the optimal location, the required
intensity of monitoring and the ideal target population.
PMID- 23154110
TI - [Kidney involvement in sarcoidosis].
AB - Sarcoidosis is a chronic multisystemic inflammatory disorder of unknown etiology,
characterized by the presence of non-necrotizing epithelioid and giant cell
granulomas. Various renal manifestations have been reported in patients with
sarcoidosis. Disorders of bone and mineral metabolism related to the
overexpression of 25-hydroxyvitamin-D1alpha-hydroxylase by alveolar and granuloma
macrophages are frequently associated with sarcoidosis. Hypercalcemia and
hypercalciuria are a major cause of renal injury predisposing to pre renal
azotemia, acute tubular necrosis, nephrolithiasis and nephrocalcinosis.
Therapeutic management of hypercalcemia includes preventive measures (limited
sunlight exposure, limited vitamin D and calcium intakes, and adequate hydration)
and specific treatment in cases of severe hypercalcemia (corticosteroid therapy,
chloroquine or ketoconazole). Granulomatous tubulointerstitial nephritis is the
most common renal lesion associated with sarcoidosis leading to end stage renal
disease in some patients. In these cases, interstitial fibrosis seems to appear
early in the course of sarcoidosis and is a major prognostic factor requiring
rapid corticosteroid therapy to reduce the risk of severe renal impairment.
Membranous nephropathy seems to be the most frequent glomerular disease that may
occur in association with sarcoidosis. Among kidney allograft recipients, the
risk of recurrence of granulomatous tubulointerstitial nephritis is high and may
have a negative impact on the graft survival.
PMID- 23154111
TI - [Aspirin for secondary prevention of venous thromboembolism. WARFASA: far from
being conclusive].
PMID- 23154112
TI - Cardiorespiratory variability following repeat acute hypoxia in the conscious SHR
versus two normotensive rat strains.
AB - A link between exaggerated chemoreceptor sensitivity and hypertension has been
documented in the spontaneously hypertensive rat (SHR) but has also been
questioned when comparisons with normotensive strains other than the Wistar Kyoto
(WKY) rat are made. To further evaluate the link between hypertension and
chemoreflex sensitivity, changes in cardiorespiratory variability in response to
three successive bouts of 5 min of hypoxia (21%->10%) were evaluated in conscious
male SHR, and WKY and Sprague Dawley (SD) rats (n=7-8/group). In response to the
first bout of hypoxia, the change in respiratory frequency (RF) was greatest in
the SHR, but the increase in mean arterial pressure (MAP) was similar in both
SHRs and WKY rats and all strains demonstrated a similar rise in heart rate (HR).
All strains showed some level of response accommodation during subsequent bouts
of hypoxia. Spectral analysis of HR variability identified a significant
difference in high frequency (HF) power between strains during hypoxia, including
an increase in HF power in the WKY rats, a decrease in the SHRs and little
overall change in the SD rats. Alternatively, all strains demonstrated a rise in
systolic arterial pressure (SAP) variability in the low frequency (LF) range in
response to hypoxia but the increase was greatest in the SHR. Since SAP LF power
is linked to vasosympathetic tone, these results support the hypothesis that
essential hypertension is linked to exaggerated sympathetic responses to
chemoreceptor stimulation but confirm that estimation of augmented reflex
function cannot be determined by quantifying simple changes in MAP or HR.
PMID- 23154113
TI - [Prevalence of metabolic syndrome, its relationship with mental health (anger)
and sociodemographic characteristics in women residing in central district of
Malatya: a cross-sectional observational study].
PMID- 23154114
TI - The difficulties during transcatheter aortic valve implantation and appropriate
precautions.
PMID- 23154115
TI - A challenging case of transcatheter aortic valve implantation under left main
coronary artery protection.
PMID- 23154116
TI - Left atrial appendix thrombus presenting with acute coronary syndrome in a
patient with rheumatic mitral stenosis.
PMID- 23154117
TI - Psychological problems in patients awaiting coronary angiography: a preliminary
study.
PMID- 23154118
TI - Double outlet right ventricle: Fallot type or non-Fallot type.
PMID- 23154119
TI - [Video of minimally invasive totally endoscopic surgical treatment of a myxoma on
the mitral valve].
PMID- 23154120
TI - [Electrocardiography in a patient with orthotopic cardiac transplantation].
PMID- 23154121
TI - The light of inflammation in the darkness of the coronary slow flow phenomenon.
PMID- 23154122
TI - An interview with Prof. Dr. Richard Sutton. Interview by Sema Guneri.
PMID- 23154123
TI - Long-term outcome of paediatric-onset multiple sclerosis: a population-based
study.
AB - BACKGROUND: Age of onset of multiple sclerosis (MS) peaks in the 3rd and 4th
decades and is rarely less than 18. Robust longitudinal studies in paediatric
onset MS (POMS) are limited, and a clearer understanding of outcome could
optimise management strategies. METHODS: Patients with disease onset <18 years
were identified from a prospective population-based register. Clinical features
including presenting symptoms, time to Expanded Disability Status Scale (EDSS)
4.0, 6.0 and 8.0 and onset of secondary progression were compared with patients
with adult-onset MS (AOMS). RESULTS: 111 POMS patients were identified from a
cohort of 2068. No significant differences in sex ratio, familial recurrence,
relapse rate, ethnicity or clinical symptoms at presentation were identified
between POMS and AOMS. However, interval to second relapse was longer (5 vs 2.6
years, p=0.04) and primary progressive disease was less common (0.9% vs 8.5%,
p=0.003) in POMS than in AOMS. POMS patients also took longer to develop
secondary progressive disease (32 vs 18 years, p=0.0001) and to reach disability
milestones (EDSS 4.0, 23.8 vs 15.5 years, p<0.0001; EDSS 6.0, 30.8 vs 20.4 years,
p<0.0001; EDSS 8.0, 44.7 vs 39 years, p=0.02), but did so between 7.0 and 12
years younger than in AOMS. CONCLUSIONS: 5.4% of patients with MS have POMS (2.7%
<16 years; 0.3% <10 years) and have distinct phenotypic characteristics in early
disease. Furthermore, while patients with POMS take longer to reach disability
milestones, they do so at a younger age than their adult counterparts and could
be considered to have a poorer prognosis. Management strategies for these
patients should take account of these data.
PMID- 23154125
TI - Deep brain stimulation for dystonia.
AB - The few controlled studies that have been carried out have shown that bilateral
internal globus pallidum stimulation is a safe and long-term effective treatment
for hyperkinetic disorders. However, most recent published data on deep brain
stimulation (DBS) for dystonia, applied to different targets and patients, are
still mainly from uncontrolled case reports (especially for secondary dystonia).
This precludes clear determination of the efficacy of this procedure and the
choice of the 'good' target for the 'good' patient. We performed a literature
analysis on DBS for dystonia according to the expected outcome. We separated
those with good evidence of favourable outcome from those with less predictable
outcome. In the former group, we review the main results for primary dystonia
(generalised/focal) and highlight recent data on myoclonus-dystonia and tardive
dystonia (as they share, with primary dystonia, a marked beneficial effect from
pallidal stimulation with good risk/benefit ratio). In the latter group, poor or
variable results have been obtained for secondary dystonia (with a focus on
heredodegenerative and metabolic disorders). From this overview, the main results
and limits for each subgroup of patients that may help in the selection of
dystonic patients who will benefit from DBS are discussed.
PMID- 23154124
TI - Verbal memory is associated with structural hippocampal changes in newly
diagnosed Parkinson's disease.
AB - BACKGROUND AND OBJECTIVE: Cognitive impairment, including impairment of episodic
memory, is frequently found in newly diagnosed Parkinson's disease (PD). In this
longitudinal observational study we investigated whether performance in memory
encoding, retention, recognition and free recall is associated with reduced
hippocampal radial distance. METHODS: We analysed baseline T1-weighted brain MRI
data from 114 PD subjects without cognitive impairment, 29 PD subjects with mild
cognitive impairment and 99 normal controls from the ParkWest study. Age- and
education-predicted scores for the California Verbal Learning Test 2 (CVLT-2) and
tests of executive function were regressed against hippocampal radial distance
while adjusting for imaging centre. RESULTS: There was no association between
encoding or performance on executive tests and hippocampal atrophy in the PD
group. In the full PD sample we found bilaterally significant associations
between lower delayed free recall scores and hippocampal atrophy in the CA1, CA3
and subiculum area (left, p=0.0013; right, p=0.0082). CVLT-2 short delay free
recall scores were associated with bilateral hippocampal CA1 and subicular
atrophy in the full PD sample (left, p=0.013; right, p=0.047). CVLT-2 recognition
scores showed a significant association with right-sided subicular and CA1
atrophy in the full PD sample (p=0.043). CONCLUSIONS: At the time of PD
diagnosis, subjects' verbal memory performance in recall and recognition are
associated with atrophy of the hippocampus, while encoding is not associated with
hippocampal radial distance. We postulate that impaired recall and recognition
might reflect deficient memory consolidation at least partly due to structural
hippocampal changes.
PMID- 23154126
TI - Changes in quality of life scores with intravenous immunoglobulin or
plasmapheresis in patients with myasthenia gravis.
AB - BACKGROUND: Intravenous immunoglobulin (IVIG) and plasmapheresis (plasma exchange
(PLEX)) have comparable efficacy in reducing the Quantitative Myasthenia Gravis
Score for disease severity (QMGS) in patients with moderate to severe myasthenia
gravis (MG). OBJECTIVE: To determine if the improvement in the quality of life
(QOL) after immunomodulation is comparable with either IVIG or PLEX. METHODS: 62
patients participated in the MG-QOL-60 study, completing the questionnaire at
baseline and at day 14 after treatment. The MG-QOL-15 scores were computed from
the MG-QOL-60 questionnaire responses. We analysed the change in the QOL scores
from baseline to day 14 in both treatment groups. RESULTS: The scores in both QOL
scales decreased at day 14 in the IVIG and PLEX groups, without significant
difference between groups (QOL-15: IVIG -5.7 +/- 8.5, PLEX: -7.0 +/- 7.6, p=0.52;
QOL-60: IVIG -13.3 +/- 16.9, PLEX -18.5 +/- 22.0, p = 0.41). The improvement in
QOL showed a good correlation with the decrease in QMGS. There was an excellent
correlation between the MG-QOL-15 and MG-QOL-60 scores at baseline and at day 14.
CONCLUSIONS: This study of MG-QOL changes supports recent findings that IVIG and
PLEX are comparable in the treatment of patients with moderate to severe MG and
worsening symptoms. Furthermore, our study supports the use of the MG-QOL-15 as a
secondary outcome measure in future clinical trials in MG.
PMID- 23154127
TI - Modulation of the cellular redox status by the Alternaria toxins alternariol and
alternariol monomethyl ether.
AB - The mycotoxin alternariol (AOH) has been reported to possess genotoxic
properties, inducing enhanced levels of DNA damage after only 1 h of incubation.
In the present study we addressed the question whether the induction of oxidative
stress might contribute to the genotoxic effects of AOH or its naturally
occurring monomethylether (AME). In the dichlorofluorescein (DCF) assay,
treatment of HT29 cells for 1 h enhanced the formation of dichlorofluorescein,
indicative for ROS formation. The total glutathione (tGSH) was transiently
decreased. In accordance with the results of the DCF assay, AOH and AME enhanced
the proportion of the transcription factor Nrf2 in the nucleus. Concomitantly,
the Nrf2/ARE-dependent genes gamma-glutamylcysteine ligase (gamma-GCL) and
glutathione-S-transferase (GSTA1/2) showed enhanced transcript levels. After 24 h
of incubation this effect was also reflected on the protein level by an increase
of GST activity. However, in spite of the positive DCF assay and the activation
of the redox-sensitive Nrf2/ARE-pathway, the level of oxidative DNA damage,
measured in the comet assay by the addition of formamidopyrimidine-DNA
glycosylase (fpg) remained unaffected. Of note, after 3 h of incubation no
significant DNA damaging potential of AOH and AME was detectable, indicating
either inactivation of the compounds or enhanced DNA repair. In summary, the
mycotoxins AOH and AME were found to modulate the redox balance of HT29 cells but
without apparent negative effect on DNA integrity.
PMID- 23154128
TI - Smooth muscle cells in human atherosclerosis: proteomic profiling reveals
differences in expression of Annexin A1 and mitochondrial proteins in carotid
disease.
AB - Smooth muscle cells (SMC) contribute to the development and stability of
atherosclerotic lesions. The molecular mechanisms that mediate their properties
are incompletely defined. We employed proteomics and in vitro functional assays
to identify the unique characteristics of intimal SMC isolated from human carotid
endarterectomy specimens and medial SMC from thoracic aortas and carotids. We
verified our findings in the Tampere Vascular Study. Human atheroma-derived SMC
exhibit decreased expression of mitochondrial proteins ATP Synthase subunit-beta
and Aldehyde dehydrogenase 2, and decreased mitochondrial activity when compared
to control SMC. Moreover, a comparison between plaque-derived SMC isolated from
patients with or without recent acute cerebrovascular symptoms uncovered an
increase in Annexin A1, an endogenous anti-inflammatory protein, in the
asymptomatic group. The deletion of Annexin A1 or the blockade of its signaling
in SMC resulted in increased cytokine production at baseline and after
stimulation with the pro-inflammatory cytokine Tumor Necrosis Factor alpha. In
summary, our proteomics and biochemical analysis revealed mitochondrial damage in
human plaque-derived SMC as well as a role of Annexin A1 in reducing the
production of pro-inflammatory mediators in SMC.
PMID- 23154129
TI - [Sclerosing epithelioid fibrosarcoma of the paravertebral column. Case report and
literature review].
AB - Sclerosing epithelioid fibrosarcoma (SEF) is a rare variant of low-grade
fibrosarcoma, with specific histological and immunohistochemical features and a
poor prognosis. We report a case of SEF of the paravertebral column in a 49-year
old male who presented a paraspinal mass with extension into the L4-L5 neural
foramen and invasion of the L5 nerve root. Histology of the tumourectomy specimen
and its immunohistochemical study led to the diagnosis of SEF. This case was
particularly unusual due to its paravertebral column location and, despite its
low grade, illustrates the malignant potential of SEF.
PMID- 23154130
TI - [The history of Spanish neurosurgery: the Valencian school: J.J. Barcia Goyanes].
AB - Professor Juan Jose Barcia-Goyanes started neurosurgical practice from anatomy
and neuropsychiatry in response to a vacancy at a department known as "Nervous
diseases", in 1931 at Hospital General in Valencia, Spain. Since the first
intervention, based on the methods and surgical instruments already used in
Europe and the U.S.A., the neurosurgical practice became the mainstay of the
department, from which other auxiliary specialties emerged, such as
neuroradiology, neurophysiology, neuropathology and also new techniques such as
stereotactic surgery, functional neurosurgery and palencephalography. This year,
the department celebrates its 80th anniversary. The broad spectrum of Prof.
Barcia's scientific work included fields like neurology, neurosurgery and
psychiatry, as well as anthropology, medical thought, history of medicine,
morphology and history of anatomical language in his work "Onomatologica
anatomica nova", in addition to an interesting poetic work. He was a founding
member of the Luso-Spanish Neurosurgical Society and the Neurosurgical Society of
Levante.
PMID- 23154131
TI - [First intraoperative magnetic resonance imaging in a Spanish hospital of the
public healthcare system: initial experience, feasibility and difficulties in our
environment].
AB - OBJECTIVE: Intraoperative MRI is considered the gold standard among all
intraoperative imaging technologies currently available. Its main indication is
in the intraoperative detection of residual disease during tumour resections. We
present our initial experience with the first intraoperative low-field MRI in a
Spanish hospital of the public healthcare system. We evaluate its usefulness and
accuracy to detect residual tumours and compare its intraoperative results with
images obtained postoperatively using conventional high-field devices. MATERIAL
AND METHODS: We retrospectively reviewed the first 21 patients operated on the
aid of this technology. Maximal safe resection was the surgical goal in all
cases. Surgeries were performed using conventional instrumentation and the
required assistance in each case. RESULTS: The mean number of intraoperative
studies was 2.3 per procedure (range: 2 to 4). Intraoperative studies proved that
the surgical goal had been achieved in 15 patients (71.4%), and detected residual
tumour in 6 cases (28.5%). After comparing the last intraoperative image and the
postoperative study, 2 cases (9.5%) were considered as "false negatives".
CONCLUSIONS: Intraoperative MRI is a safe, reliable and useful tool for guided
resection of brain tumours. Low-field devices provide images of sufficient
quality at a lower cost; therefore their universalisation seems feasible.
PMID- 23154132
TI - Three-step pathway engineering results in more incidence rate and higher emission
of nerolidol and improved attraction of Diadegma semiclausum.
AB - The concentration and ratio of terpenoids in the headspace volatile blend of
plants have a fundamental role in the communication of plants and insects. The
sesquiterpene (E)-nerolidol is one of the important volatiles with effect on
beneficial carnivores for biologic pest management in the field. To optimize de
novo biosynthesis and reliable and uniform emission of (E)-nerolidol, we
engineered different steps of the (E)-nerolidol biosynthesis pathway in
Arabidopsis thaliana. Introduction of a mitochondrial nerolidol synthase gene
mediates de novo emission of (E)-nerolidol and linalool. Co-expression of the
mitochondrial FPS1 and cytosolic HMGR1 increased the number of emitting
transgenic plants (incidence rate) and the emission rate of both volatiles. No
association between the emission rate of transgenic volatiles and their growth
inhibitory effect could be established. (E)-Nerolidol was to a large extent
metabolized to non-volatile conjugates.
PMID- 23154133
TI - How the rehabilitation environment influences patient perception of service
quality: a qualitative study.
AB - OBJECTIVE: To identify elements of the environment that patients consider when
evaluating the quality of a care experience in outpatient rehabilitation
settings. DESIGN: A qualitative study using a modified grounded theory approach.
Data collection used semistructured interviewing during 9 focus groups. SETTING:
Three postacute ambulatory centers in metropolitan areas. PARTICIPANTS: Adults
(N=57; 33 men, 24 women) undergoing outpatient rehabilitation for musculoskeletal
conditions/injuries. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Not
applicable. RESULTS: Participants perceived the quality of rehabilitation service
on the basis of their experiences with environmental factors, including 3
physical factors (facility design, ambient conditions, and social factors) and 4
organizational factors (duration of attendance, interruptions during delivery of
care, waiting times in the sequence of treatment, and patient safety).
CONCLUSIONS: This study identifies the specific environmental attributes that
patients consider important when evaluating the quality of outpatient
rehabilitation settings and develops a patient-based framework for assessing the
overall perception of service quality. Further research should work to develop
self-report questionnaires about patient experiences with the environment in
rehabilitation services to provide empirical and quantitative evidence.
PMID- 23154134
TI - Correlation between voluntary cough and laryngeal cough reflex flows in patients
with traumatic brain injury.
AB - OBJECTIVE: To correlate voluntary cough and laryngeal cough reflex (LCR) flows in
patients with traumatic brain injury (TBI). DESIGN: Cross-sectional study.
SETTING: University rehabilitation hospital. PARTICIPANTS: Patients with TBI
(n=25) and healthy controls (n=48). INTERVENTIONS: Not applicable. MAIN OUTCOME
MEASURES: Peak cough flows (PCFs) and LCR flows were measured using a peak flow
meter at the oral-nasal interface. The largest value of 3 attempts was recorded
for PCF and LCR, respectively. LCR was elicited by 20% solution of pharmaceutic
grade citric acid dissolved in sterile .15M NaCl solution that was inhaled from a
nebulizer. RESULTS: PCF was 447.4 +/- 99.0 L/min in the control group and 211.7
+/- 58.2 L/min in the patient group. LCR was 209.2 +/- 63.8L/min in the control
group and 170.0 +/- 59.7 L/min in the patient group. Both PCF (P=.000) and LCR
(P=.013) were significantly reduced in patients with TBI compared to that of the
control group. LCR was strongly related to the PCF in both control (R=.645;
P=.000) and patient (R=.711; P=.000) groups. CONCLUSIONS: As LCR can be measured
as a numerical value and significantly correlates with PCF, LCR can be used to
estimate cough ability of patients with TBI who cannot cooperate with PCF
measurement.
PMID- 23154135
TI - Joint line tenderness and McMurray tests for the detection of meniscal lesions:
what is their real diagnostic value?
AB - OBJECTIVES: To assess the interobserver concordance of the joint line tenderness
(JLT) and McMurray tests, and to determine their diagnostic efficiency for the
detection of meniscal lesions. DESIGN: Prospective observational study. SETTING:
Orthopedics outpatient clinic, university hospital. PARTICIPANTS: Patients (N=60)
with suspected nonacute meniscal lesions who underwent knee arthroscopy.
INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patients were examined by 3
independent observers with graded levels of experience (>10y, 3y, and 4mo of
practice). The interobserver concordance was assessed by Cohen-Fleiss kappa
statistics. Accuracy, negative and positive predictive values for prevalence 10%
to 90%, positive (LR+) and negative (LR-) likelihood ratios, and the Bayesian
posttest probability with a positive or negative result were also determined. The
diagnostic value of the 2 tests combined was assessed by logistic regression.
Arthroscopy was used as the reference test. RESULTS: No interobserver concordance
was determined for the JLT. The McMurray test showed higher interobserver
concordance, which improved when judgments by the less experienced examiner were
discarded. The whole series studied by the "best" examiner (experienced
orthopedist) provided the following values: (1) JLT: sensitivity, 62.9%;
specificity, 50%; LR+, 1.26; LR-, .74; (2) McMurray: sensitivity, 34.3%;
specificity, 86.4%; LR+, 2.52; LR-, .76. The combination of the 2 tests did not
offer advantages over the McMurray alone. CONCLUSIONS: The JLT alone is of little
clinical usefulness. A negative McMurray test does not modify the pretest
probability of a meniscal lesion, while a positive result has a fair predictive
value. Hence, in a patient with a suspected meniscal lesion, a positive McMurray
test indicates that arthroscopy should be performed. In case of a negative
result, further examinations, including imaging, are needed.
PMID- 23154136
TI - Electron scattering cross-section measurements in ESEM.
AB - A review, analysis and discussion on the derivation and measurement of electron
scattering cross-sections of gases mostly used in environmental scanning electron
microscopy is presented together with some previously unreported experimental
material. There are significant differences in values published for cross
sections of such gases. Scanning the electron beam across a clean edge seems to
be a most reliable technique to produce and measure beam profiles, from which the
scattering cross-sections can be obtained with high accuracy and reliability.
Results based on this method produce an excellent agreement with a theoretically
derived value of scattering cross-section using an average factor of energy loss
for all inelastic collisions. The discussion addresses the difficulties involved
and provides alternative ways to reliably obtain cross-sections as a function of
accelerating voltage in the range mostly used in environmental scanning electron
microscopy.
PMID- 23154137
TI - High cyst concentrations of the potentially toxic dinoflagellate Alexandrium
tamarense species complex in Bedford Basin, Halifax, Nova Scotia, Canada.
AB - We report a large cyst bed of the potentially toxic and bloom-forming
dinoflagellate Alexandrium tamarense species complex in bottom sediments from the
port of Halifax, Nova Scotia, Canada. The average cyst concentrations of that
species ranged from 4033+/-2647 to 220872+/-148086 cysts g-1 of dry sediments and
the highest concentrations were found near ship terminals in Bedford Basin.
Although this species is endemic to this region, our work strongly suggests that
some of the cysts of A. tamarense species complex found in the port of Halifax
were introduced through discharged ballast water and sediments.
PMID- 23154138
TI - Persistent organic pollutants and stable isotopes in pinnipeds from King George
Island, Antarctica.
AB - In the present work, fat, skin, liver and muscle samples from Leptonychotes
weddellii (Weddell seal, n=2 individuals), Lobodon carcinophagus (crabeater seal,
n=2), Arctocephalus gazella (Antarctic fur seal, n=3) and Mirounga leonina
(southern elephant seal, n=1) were collected from King George Island, Antarctica,
and analysed for POPs (PCBs, organochlorine pesticides and PBDEs) and stable
isotopes (delta13C and delta15N in all tissues but fat). PBDEs could be found in
only one sample (L. weddellii fat). Generally, PCBs (from 74 to 523 ng g-1 lw),
DDTs (from 14 to 168 ng g-1 lw) and chlordanes (from 9 to 78 ng g-1 lw) were the
prevailing compounds. Results showed a clear stratification in accordance with
ecological data. Nonetheless, stable isotope analyses provide a deeper insight
into fluctuations due to migrations and nutritional stress. Correlation between
delta(15)N and pollutants suggests, to some degree, a considerable ability to
metabolize and/or excrete the majority of them.
PMID- 23154139
TI - Urban breakwaters as reef fish habitat in the Persian Gulf.
AB - Breakwaters and related structures dominate near-shore environments in many
Persian Gulf countries, but little is known of their ecology. To examine the
influence of wave exposure on fish communities we surveyed exposed and sheltered
breakwaters seasonally over 2 years and compared these with natural reef
assemblages. Species richness and adult, juvenile, and total abundance were
generally comparable among the three habitat types each season. However,
differences in multivariate community structure indicated that each habitat
contained a distinct assemblage, with strongest difference between sheltered
breakwaters and the exposed natural reef. All communities were characterized by
marked seasonality; abundance and richness were generally higher in the warmer
seasons (summer, fall) than during cooler periods (winter, spring), and there
were related seasonal changes in community structure, particularly on the natural
reef. Results indicate that breakwaters are important fish habitats, but that
breakwater communities vary with wave exposure and are distinct from natural
reefs.
PMID- 23154140
TI - An integrative method for the evaluation, monitoring, and comparison of seagrass
habitat structure.
AB - Assessing environmental condition is essential for the management of coasts and
their resources, but better management decisions occur when large databases are
simplified into more manageable units of information. Here we present the habitat
structure index (HSI), which enables rapid assessment and direct comparison of
seagrass habitat structure using scores of 0 (poor) to 100 (excellent) based on
integrating five habitat variables: area, continuity, proximity, percentage
cover, and species identity. Acquiring data to calculate the HSI can be done in
situ or from video recordings, and requires relatively simple methodology of belt
transects, estimating percentage cover, and basic taxonomy. Spatiotemporal
comparisons can usefully identify locations and periods of seagrass habitat
change, potentially providing an early warning indicator of habitat damage and
decline in environmental quality. Overall, the integrative approach of the HSI
represents a step toward simplifying the exchange of environmental information
among researchers, coastal managers, and governing bodies.
PMID- 23154141
TI - Effects of heat stress on development, quality and survival of Bos indicus and
Bos taurus embryos produced in vitro.
AB - Heat stress is an important cause of poor development and low survival rates in
bovine embryos. Experiments were conducted to test the hypothesis that Bos
indicus embryos are more resistant to heat stress than are Bos taurus embryos. In
experiment 1, Nelore and Jersey embryos from oocyte pick-up-derived oocytes were
submitted to heat stress (96 hours post-insemination, 41 degrees C, 6 hours),
developmental ratios were assessed at Day 7 (Day 0 = day of fertilization), and
blastocysts were frozen for RNA extraction. Experiment 2 evaluated expression of
COX2, CDX2, HSF1, and PLAC8 in previously frozen blastocysts. In experiment 3,
Nellore and Angus embryos from oocyte pick-up-derived oocytes were submitted to
heat stress (96 hours post-insemination, 41 degrees C, 12 hours) and transferred
to recipients on Day 7. In experiment 4, embryos developed as in experiment 3
were fixed for Terminal deoxynucleotidyl transferase dUTP nick end labeling
labeling and total cell counting. In experiment 1, heat stress decreased the
percentage of Jersey oocytes that became blastocysts, but had no effect on
Nellore embryos (34.6%, 25.0%, 39.5%, and 33.0% for Jersey control, Jersey heat
stressed, Nellore control, and Nellore heat-stressed oocytes, respectively; P <
0.05). In experiment 2, heat stress decreased (P < 0.05) expression of CDX2 and
PLAC8, with higher expression of these genes in Nellore embryos than in Jersey
embryos. Heat stress also decreased (P < 0.05) expression of COX2 in Jersey
embryos, but had no effect on Nellore embryos. Expression of HSF1 was decreased
(P < 0.05) by heat stress in both breeds, with a greater effect in Nellore
embryos. In experiment 3, heat stress tended (P = 0.1) to decrease the percentage
of pregnancies among cows (Day 30 to 35) that received Angus embryos. In
experiment 4, heat stress increased (P < 0.05) the percentage of apoptotic
blastomeres, but had no breed-specific effects. In addition, Nellore embryos had
fewer (P < 0.05) Terminal deoxynucleotidyl transferase dUTP nick end labeling-
positive blastomeres than did Angus embryos. We concluded that the detrimental
effects of heat stress were dependent upon embryo breed and were more evident in
Bos taurus embryos than in Bos indicus embryos.
PMID- 23154142
TI - Ovarian response and embryo gene expression patterns after nonsuperovulatory
gonadotropin stimulation in primiparous rabbits does.
AB - Ovarian stimulation with equine chorionic gonadotropin (eCG) is largely used in
animal reproductive technologies to provide a larger number of oocytes and
embryos and to improve the reproductive outcome. However, the consequences of
maternal treatment with eCG on embryo gene expression patterns are not widely
studied. The aim of this work was to assess the ovarian response (preovulatory
follicular population, oocyte maturation, ovulation rate, and serum steroid
concentrations), the early embryo survival and gene expression patterns of a
panel of quality-genes involved in glucose intake, oxidative stress, apoptosis,
proliferation, implantation, and fetal growth in embryos of lactating rabbits
treated with eCG. A total of 34 primiparous rabbit does (Oryctolagus cuniculus)
were randomly distributed at Day 23 postpartum into a treatment group receiving a
unique nonsuperovulatory dose (25 IU) of eCG (eCG group; N = 17 does); or a
control group without eCG treatment previously to artificial insemination
(control group; N = 17 does). After 48 hours, 8 does of each group were
euthanized and their ovarian response was studied. The rest of animals were
artificially inseminated and their ovulation was induced with a GnRH analogue.
Embryos were recovered 3.5 days later. The oocytes retrieved for in vitro
maturation showed no differences in metaphase II rate in both experimental
groups, although oocyte cytoplasmic maturation, in terms of cortical granule
migration rate, was improved in eCG-treated does (P < 0.05). The mean number of
preovulatory follicles was similar between groups but the ovulation rate was
significantly higher in eCG-treated does compared with does not stimulated (P <
0.05). No differences were found in serum estradiol and progesterone
concentrations of does the day of oocyte and embryo recovery, respectively.
However, progesterone:estradiol ratio was slightly increased in eCG group on
embryo recovery day (P = 0.1). The percentage of embryos recovered at the
blastocyst stage was also increased in eCG-treated does (P < 0.05), nevertheless,
there were no differences in the gene expression patterns of candidate genes
SLC2A4, IGF1R, IGF2R, SHC1-SHC, TP53, PTGS2, and PLAC8; except for the
transcripts of SOD1 mRNA which were downregulated in eCG-derived embryos (P <
0.05). In conclusion, the administration of eCG improves ovulation rate, oocyte
cytoplasmic maturation, and blastocyst formation in primiparous rabbit does
inseminated on Day 25 postpartum. Although it seems not to influence the gene
expression patterns studied, a lower antioxidant defense of embryos developed
after the maternal eCG treatment is suggested.
PMID- 23154143
TI - Differential gene expressions in testes of L2 strain Taiwan country chicken in
response to acute heat stress.
AB - Acute heat stress affects genes involved in spermatogenesis in mammals. However,
there is apparently no elaborate research on the effects of acute heat stress on
gene expression in avian testes. The purpose of this study was to investigate
global gene expression in testes of the L2 strain of Taiwan country chicken after
acute heat stress. Twelve roosters, 45 weeks old, were allocated into four
groups, including control roosters kept at 25 degrees C, roosters subjected to
38 degrees C acute heat stress for 4 hours without recovery, with 2-hour
recovery, and with 6-hour recovery, respectively. Testis samples were collected
for RNA isolation and microarray analysis. Based on gene expression profiles, 169
genes were upregulated and 140 genes were downregulated after heat stress using a
cutoff value of twofold or greater change. Based on gene ontology analysis,
differentially expressed genes were mainly related to response to stress,
transport, signal transduction, and metabolism. A functional network analysis
displayed that heat shock protein genes and related chaperones were the major
upregulated groups in chicken testes after acute heat stress. A quantitative real
time polymerase chain reaction analysis of mRNA expressions of HSP70, HSP90AA1,
BAG3, SERPINB2, HSP25, DNAJA4, CYP3A80, CIRBP, and TAGLN confirmed the results of
the microarray analysis. Because the HSP genes (HSP25, HSP70, and HSP90AA1) and
the antiapoptotic BAG3 gene were dramatically altered in heat-stressed chicken
testes, we concluded that these genes were important factors in the avian testes
under acute heat stress. Whether these genes could be candidate genes for
thermotolerance in roosters requires further investigation.
PMID- 23154145
TI - Why do singletons conceived after assisted reproduction technology have adverse
perinatal outcome? Systematic review and meta-analysis.
AB - BACKGROUND: Assisted reproduction technology (ART) is used worldwide, at
increasing rates, and data show that some adverse outcomes occur more frequently
than following spontaneous conception (SC). Possible explanatory factors for the
well-known adverse perinatal outcome in ART singletons were evaluated. METHODS:
PubMed and Cochrane databases from 1982 to 2012 were searched. Studies using
donor or frozen oocytes were excluded, as well as those with no control group or
including <100 children. The main outcome measure was preterm birth (PTB defined
as delivery <37 weeks of gestation), and a random effects model was used for meta
analyses of PTB. Other outcomes were very PTB, low-birthweight (LBW), very LBW,
small for gestational age and perinatal mortality. RESULTS: The search returned
1255 articles and 65 of these met the inclusion criteria. The following were
identified as predictors for PTB in singletons: SC in couples with time to
pregnancy (TTP) > 1 year versus SC singletons in couples with TTP <= 1 year
[adjusted odds ratio (AOR) 1.35, 95% confidence interval (CI) 1.22, 1.50];
IVF/ICSI versus SC singletons from subfertile couples (TTP > 1 year; AOR 1.55,
95% CI 1.30, 1.85); conception after ovulation induction and/or intrauterine
insemination versus SC singletons where TTP <= 1 year (AOR 1.45, 95% CI 1.21,
1.74); IVF/ICSI singletons versus their non-ART singleton siblings (AOR 1.27, 95%
CI 1.08, 1.49). The risk of PTB in singletons with a 'vanishing co-twin' versus
from a single gestation was AOR of 1.73 (95% CI 1.54, 1.94) in the narrative
data. ICSI versus IVF (AOR 0.80, 95% CI 0.69-0.93), and frozen embryo transfer
versus fresh embryo transfer (AOR 0.85, 95% CI 0.76, 0.94) were associated with a
lower risk of PTB. CONCLUSIONS: Subfertility is a major risk factor for adverse
perinatal outcome in ART singletons, however, even in the same mother an ART
singleton has a poorer outcome than the non-ART sibling; hence, factors related
to the hormone stimulation and/or IVF methods per se also may play a part.
Further research is required into mechanisms of epigenetic modification in human
embryos and the effects of cryopreservation on this, whether milder ovarian
stimulation regimens can improve embryo quality and endometrial conditions, and
whether longer culture times for embryos has a negative influence on the
perinatal outcome.
PMID- 23154144
TI - Equine chorionic gonadotropin improves the efficacy of a timed artificial
insemination protocol in buffalo during the nonbreeding season.
AB - Two experiments were conducted to evaluate the effects of equine chorionic
gonadotropin (eCG) treatment on ovarian follicular response, luteal function, and
pregnancy in buffaloes subjected to a timed artificial insemination (TAI)
protocol during the nonbreeding season. In experiment 1, 59 buffalo cows were
randomly assigned to two groups (with and without eCG). On the first day of the
synchronization protocol (Day 0), cows received an intravaginal progesterone (P4)
device plus 2.0 mg estradiol benzoate im. On Day 9, the P4 device was removed,
all cows were given 0.150 mg PGF(2alpha) im, and half were given 400 IU eCG im.
On Day 11, all cows were given 10 MUg of buserelin acetate im (GnRH). Transrectal
ultrasonography of the ovaries was performed on Days 0 and 9 to determine the
presence and diameter of the largest follicle; between Days 11 and 14 (12 hours
apart), to evaluate the dominant follicle diameter and the interval from device
removal to ovulation; and on Days 16, 20, and 24 to measure CL diameter. Blood
samples were collected on Days 16, 20, and 24 to measure serum P4. In experiment
2, 256 buffaloes were assigned to the same treatments described in experiment 1,
and TAI was performed 16 hours after GnRH treatment. Pregnancy diagnosis was
performed by ultrasonography 30 days after TAI. Treatment with eCG increased the
maximum diameter of dominant follicles (P = 0.09), ovulation rate (P = 0.05), CL
diameter (P = 0.03), and P4 concentrations (P = 0.01) 4 days after TAI, and
pregnancy per AI (52.7%, 68/129 vs. 39.4%, 50/127; P = 0.03). Therefore, eCG
improved ovarian follicular response, luteal function during the subsequent
diestrus, and fertility for buffalo subjected to a TAI synchronization protocol
during the nonbreeding season.
PMID- 23154146
TI - Toward a non-invasive screening tool for differentiation of pancreatic lesions
based on intra-voxel incoherent motion derived parameters.
AB - Early recognition of and differential diagnosis between pancreatic cancer and
chronic pancreatitis is an important step in successful therapy. Parameters of
the IVIM (intra-voxel incoherent motion) theory can be used to differentiate
between those lesions. The objective of this work is to evaluate the effects of
rigid image registration on IVIM derived parameters for differentiation of
pancreatic lesions such as pancreatic cancer and solid mass forming pancreatitis.
The effects of linear image registration methods on reproducibility and accuracy
of IVIM derived parameters were quantified on MR images of ten volunteers. For
this purpose, they were evaluated statistically by comparison of registered and
unregistered parameter data. Further, the perfusion fraction f was used to
differentiate pancreatic lesions on eleven previously diagnosed patient data
sets. Its diagnostic power with and without rigid registration was evaluated
using receiver operating curves (ROC) analysis. The pancreas was segmented
manually on MR data sets of healthy volunteers as well as the patients showing
solid pancreatic lesions. Diffusion weighted imaging was performed in 10 blocks
of breath-hold phases. Linear registration of the weighted image stack leads to a
3.7% decrease in variability of the IVIM derived parameter f due to an improved
anatomical overlap of 5%. Consequently, after registration the area under the
curve in the ROC-analysis for the differentiation approach increased by 2.7%. In
conclusion, rigid registration improves the differentiation process based on f
values.
PMID- 23154147
TI - Curricular disconnects in learning communication skills: what and how students
learn about communication during clinical clerkships.
AB - OBJECTIVE: In many medical schools, formal training in clinical communication
skills (CCS) mainly occurs during pre-clinical training prior to clinical
rotations. The current research examined student perceptions of both what and how
they learn about CCS during clinical rotations. METHODS: During 2008 and 2009,
4th year medical students were invited to participate in interviews focused on
learning of CCS during clinical rotations. Interview transcripts were analyzed to
identify salient themes in their discussions of CCS in clinical learning
experiences. RESULTS: 107 senior students participated and reported learning CCS
during clinical rotations mainly by: (1) observing faculty and residents; (2)
conducting interviews themselves; and (3) through feedback on patient
presentations. Teacher role modeling tended to not reinforce what they had
learned pre-clinically about CCS and clinical teachers rarely discussed CCS.
Feedback on patient presentations affected students' communication styles, at
times prompting them to omit use of CCS they had learned pre-clinically.
CONCLUSIONS: Students reported that clinical learning experiences often do not
reinforce the CCS they learn pre-clinically. PRACTICAL IMPLICATIONS: Disconnects
between pre-clinical and clinical CCS teaching need to be reconciled through more
explicit pedagogical attention to CCS issues during clinical rotations both in
the formal and informal curriculum.
PMID- 23154148
TI - Time to sign: The relationship between health literacy and signature time.
AB - OBJECTIVE: To evaluate the relationship between amount of time taken to sign
one's name and health literacy. METHODS: A prospective, one time assessment was
conducted on a convenience sample of 98 patients recruited in an inner-city
outpatient internal medicine clinic. The amount of time required to sign (i.e.
initiation to completion of writing) was measured by stopwatch. Health literacy
was measured with the REALM. RESULTS: The sample averaged 54.1 (SD 16.2) years of
age. Twenty-seven percent had less than high school education and 33% had a
terminal general equivalency diploma or high school degree. The time required to
sign ranged from 0.91 to 21.3s. Sixty-two percent of the sample had health
literacy challenges. Signature time was longest for those with inadequate health
literacy (mean 10.0 s), compared with marginal (7.3s) and adequate (4.7s, p <=
0.001). Signature time remained significant in a logistic regression model after
controlling for education and age (AOR = 0.785, CI = 0.661-0.932). CONCLUSION:
Individuals with signatures completed in six seconds or less were highly likely
to display adequate health literacy. PRACTICE IMPLICATIONS: Signature time may
offer a practical and quick approach to health literacy screening in the health
care setting.
PMID- 23154149
TI - The evolution of midwifery education at the master's level: a study of Swedish
midwifery education programmes after the implementation of the Bologna process.
AB - In Europe, midwifery education has undergone a number of reforms in the past few
decades. In several countries, it has shifted from vocational training to
academic education. The higher education reform, known as the "Bologna process"
aimed to create convergence in higher education among a number of European
countries and enhance opportunities for mobility, employment and collaborative
research. It also indicated a transparent and easily compared system of academic
degrees, generating a new educational system in three cycles. This study explores
the implementation of the process in Sweden when the midwifery education was
transferred from diploma to postgraduate or master's level. The aim of this study
was to analyse how the implementation of the Bologna process in the Swedish
higher education system has impacted midwifery education programmes in the
country. Descriptive statistics and content analysis were employed to analyse 32
questionnaire responses from teachers and the 2009-2010 curricula and syllabi of
11 postgraduate midwifery education programmes at Swedish universities and
university colleges. The results revealed variations among the universities at
the major subject into the three disciplines; midwifery, nursing and caring with
different conceptualisations, even when the content was identical in the
curricula to that of the midwifery professional knowledge base. Implementation of
the new reform not only has accelerated the academisation process, but also puts
higher demand on the students and requires higher competencies among teachers to
involve more evidence-based knowledge, seminars, independent studies and a
postgraduate degree project in the major subject. Thus the students earn not only
a diploma in midwifery, but also a master's degree in the major subject, which
affords the opportunity for an academic career. But still there is a tension
between professional and academic education.
PMID- 23154150
TI - Understanding and improving patient experience: a national survey of training
courses provided by higher education providers and healthcare organizations in
England.
AB - BACKGROUND: Understanding and improving 'patient experience' is essential to
delivering high quality healthcare. However, little is known about the provision
of education and training to healthcare staff in this increasingly important
area. OBJECTIVES: This study aims to ascertain the extent and nature of such
provision in England and to identify how it might be developed in the future.
METHODS: An on-line survey was designed to explore training provision relating to
patient experiences. To ensure that respondents thought about patient experience
in the same way we defined patient experience training as that which aims to
teach staff: 'How to measure or monitor the experience, preferences and
priorities of patients and use that knowledge to improve their experience'.
Survey questions (n=15) were devised to cover nine consistently reported key
aspects of patient experience; identified from the research literature and
recommendations put forward by professional bodies. The survey was administered
to (i) all 180 providers of Higher Education (HE) to student/qualified doctors,
nurses and allied health professionals, and (ii) all 390 National Health Service
(NHS) trusts in England. In addition, we added a single question to the NHS 2010
Staff Survey (n=306,000) relating to the training staff had received to deliver a
good patient experience. RESULTS: Two hundred and sixty-five individuals
responded to the on-line survey representing a total of 159 different
organizations from the HE and healthcare sectors. Respondents most commonly
identified 'relationships' as an 'essential' aspect of patient experience
education and training. The biggest perceived gaps in current provision related
to the 'physical' and 'measurement' aspects of our conceptualization of patient
experience. Of the 148,657 staff who responded to the Staff Survey 41% said they
had not received patient experience training and 22% said it was not applicable
to them. CONCLUSIONS: While some relevant education courses are in place in
England, the results suggest that specific training with regard to the physical
needs and comfort of patients, and how patient experiences can be measured and
used to improve services, should be introduced. Future developments should also
focus, firstly, on involving a wider range of patients in planning and delivering
courses and, secondly, evaluating whether courses impact on the attitudes and
behaviors of different professional groups and might therefore contribute to
improved patient experiences.
PMID- 23154151
TI - Alcohol education and training in pre-registration nursing: a national survey to
determine curriculum content in the United Kingdom (UK).
AB - BACKGROUND: Alcohol-related harm impacts significantly on the health of the
population. Nurses are often among the first health professionals that many
patients with alcohol-related problems come into contact with and have been
identified as playing a key role but may be ill-prepared to respond. Future
nurses need to have the skills, knowledge and clinical confidence to respond to
patients suffering from alcohol-related harm. A pre-registration curriculum that
ensures a nursing workforce fit for practice in responding to alcohol-related
harm is necessary. OBJECTIVES: To determine the level of alcohol education and
training content in the pre-registration curriculum for nursing in the United
Kingdom (UK). To establish whether there are variations in the pre-registration
curriculum content across the UK. DESIGN: A descriptive study. SETTING: All 68 UK
Higher Education Institutions offering a total of 111 pre-registration courses
for nurses were invited to participate in the study. PARTICIPANTS: Twenty nine
completed questionnaires were returned, a response rate of 26%. The largest
number of identified responders were from England (n=15), with 3 from Scotland
and 1 each from Wales and Northern Ireland. Nine Universities chose not to
identify themselves. METHODS: An online semi-structured questionnaire survey was
used to collect the study data. RESULTS: Teaching of alcohol and alcohol related
harm was mainly delivered during the second year of a pre-registration nursing
programme provided mainly to adult and mental health students. Overall, the
majority of alcohol related content that is provided within the responding pre
registration nursing courses relates to biophysiology, aetiology, and
pharmacological and non-pharmacological interventions. CONCLUSION: This study
highlights the need for a greater and more relevant focus of alcohol education to
pre-registration nursing students of all fields of practice incorporating an
integrated approach across all years of study.
PMID- 23154152
TI - Preparation and characterization of CK2 inhibitor-loaded cyclodextrin
nanoparticles for drug delivery.
AB - Casein Kinase 2 (CK2) is a ubiquitous kinase protein currently targeted for the
treatment of some cancers. Recently, the series of indeno[1,2-b]indoles has
revealed great interest as potent and selective CK(2) ATP-competitive inhibitors.
Among them, 1-amino-5-isopropyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione
(CM1) was selected for an encapsulation study in order to improve its
biodisponibility. Its complexation was evaluated at the molecular scale, with a
series of fluorinated or hydrocarbonated amphiphilic cyclodextrins (CDs). Then
the encapsulation of CM1 within CD nanoparticles at the supramolecular level was
achieved. Nanoparticles formed between CM1 and hexakis[6-deoxy-6-(3
perfluorohexylpropanethio)-2,3-di-O-methyl]-alpha-cyclodextrin, a fluorinated
amphiphilic alpha-cyclodextrin, gave the best results in terms of encapsulation
rate, stability and drug release. These nanospheres showed an encapsulation
efficiency of 65% and a sustained release of the entrapped drug over 3h. Based on
these results, encapsulation within fluorinated amphiphilic CD nanoparticles
could be considered as a potential drug delivery system for indenoindole-type CK2
inhibitors, allowing better biodisponibility and offering perspectives for tumor
targeting development.
PMID- 23154153
TI - 21st-century alternatives to classic resurfacing techniques.
PMID- 23154154
TI - Subcutaneous pedicled V-Y advancement flap for surgical reconstruction of the
auricle of the ear.
AB - The subcutaneous pedicled V-Y advancement flap is useful for the repair of small
and medium-sized defects in areas where it is easy to obtain a good subcutaneous
pedicle (upper lip, cheek, eyebrow, and nasal tip and ala). The almost complete
absence of subcutaneous tissue on the anterior aspect of the auricle of the ear
can limit the use of this approach in this region. We present 4 patients in whom
subcutaneous pedicled V-Y advancement flaps were used to repair surgical defects
of the helix, scaphoid fossa, and antitragus, achieving a good functional and
aesthetic result in all cases.
PMID- 23154155
TI - High versus low glycemic index 3-h recovery diets following glycogen-depleting
exercise has no effect on subsequent 5-km cycling time trial performance.
AB - OBJECTIVES: Some athletes train/compete multiple times in a single day and rapid
restoration of muscle and hepatic glycogen stores is therefore important for
athletic performance. DESIGN: Randomised, counterbalanced, crossover, single
blinded study investigated the effects of low/high glycaemic index (GI) meals on
the physiological responses to a 3-h recovery period and subsequent 5-km cycling
time trial (TT). METHODS: Seven male cyclists completed glycogen-depleting
exercise followed by a 3-h recovery period, when participants consumed either a
high or low GI meal providing 2gkg(-1) BM of carbohydrate. Participants then
performed a 5-km cycling TT. Blood samples were analysed for glucose insulin,
free fatty acid (FFA) and triglyceride. RESULTS: There was no significant
difference between the median (IQR) cycling TT time of 8.5 (3.0) min in the LGI
condition and 8.4 (1.8) min in the HGI condition (p=0.45). Serum insulin was
significantly higher in the HGI condition throughout the 3-h recovery period
(p=0.025), FFA concentrations were higher in the HGI condition only at 30min into
recovery (p=0.008). The respiratory exchange ratio (p=0.028) and carbohydrate
oxidation rate (p=0.015) increased over time in the HGI condition, whereas the
rate of fat oxidation demonstrated the opposite response (p=0.001). No
significant differences between conditions were observed for any physiological
variables at the end of the 5-km TT. CONCLUSIONS: Although the GI of the two
meals indicated important metabolic differences during the recovery period, there
was no evidence suggesting these differences influenced subsequent 5-km TT
performance.
PMID- 23154156
TI - For non-exercising people, the number of steps walked is more strongly associated
with health than time spent walking.
AB - OBJECTIVE: This study examined the associations between walking (number of steps
and minutes spent) and seven health indicators, including chronic health
conditions, depressive symptoms, and blood pressure, among nonexercising people
who did not regularly engage in any non-walking moderate-to-vigorous physical
activity in Hong Kong. DESIGN: Under the FAMILY project, the number of steps per
day and minutes spent walking were measured using an accelerometer. Participants
(n=2417) whose only form of physical activity was walking were included in the
present analysis. METHODS: Three indicators of walking (number of steps, minutes
spent walking at moderate intensity, and minutes spent walking at light
intensity) was measured by accelerometer. Associations between these indicators
and seven health conditions were measured by the difference in z scores for those
with, and those without, each health condition, adjusted for age and sex.
RESULTS: The number of steps per day was significantly and inversely associated
with hypertension (difference in z=-0.22, p<0.01), cancer (difference in z=-0.43,
p<0.05), stroke (difference in z=-0.63, p<0.01), depressive symptoms (difference
in z=-0.15, p<0.01), health-related quality-of-life (difference in z=-0.13,
p<0.05), and pulse rate (difference in z=-0.11, p<0.01). By contrast, time spent
walking as measured by accelerometer was associated only with a single health
indicator (hypertension, difference in z=-0.14, p<0.05). CONCLUSIONS: Even among
non-exercising people, accumulating number of steps appears to be related to
fewer health problems and should be promoted as an accessible form of exercise,
especially for those who lack the time or ability to engage in physical activity
of at least moderate intensity.
PMID- 23154157
TI - African swine fever virus controls the host transcription and cellular machinery
of protein synthesis.
AB - Throughout a viral infection, the infected cell reprograms the gene expression
pattern in order to establish a satisfactory antiviral response. African swine
fever virus (ASFV), like other complex DNA viruses, sets up a number of
strategies to evade the host's defense systems, such as apoptosis, inflammation
and immune responses. The capability of the virus to persist in its natural hosts
and in domestic pigs, which recover from infection with less virulent isolates,
suggests that the virus displays effective mechanisms to escape host defense
systems. ASFV has been described to regulate the activation of several
transcription factors, thus regulating the activation of specific target genes
during ASFV infection. Whereas some reports have concerned about anti-apoptotic
ASFV genes and the molecular mechanisms by which ASFV interferes with inducible
gene transcription and immune evasion, less is yet known regarding how ASFV
regulates the translational machinery in infected cells, although a recent report
has shown a mechanism for favored expression of viral genes based on
compartmentalization of viral mRNA and ribosomes with cellular translation
factors within the virus factory. The viral mechanisms involved both in the
regulation of host genes transcription and in the control of cellular protein
synthesis are summarized in this review.
PMID- 23154158
TI - Newborn screening for congenital hypothyroidism.
AB - Newborn screening (NS) for congenital hypothyroidism (CH) is one of the major
achievements in preventive medicine. Most neonates born with CH have normal
appearance and no detectable physical signs. Hypothyroidism in the newborn period
is almost always overlooked, and delayed diagnosis leads to the most severe
outcome of CH, mental retardation, emphasizing the importance of NS. Blood spot
thyroid stimulating hormone (TSH) or thyroxine (T4) or both can be used for CH
screening. The latter is more sensitive but not cost-effective, so screening by
TSH or T4 is used in different programs around the world. TSH screening was shown
to be more specific in the diagnosis of CH. T4 screening is more sensitive in
detecting especially those newborns with rare hypothalamic-pituitary
hypothyroidism, but it is less specific with a high frequency of false positives
mainly in low birth weight and premature infants. The time at which the sample is
taken may vary. In the majority of the centers, blood is obtained from a heel
prick after 24 hours of age to minimize the false positive high TSH due to the
physiological neonatal TSH surge that elevates TSH levels and causes dynamic T4
and T3 changes in the first 1 or 2 days after birth. Early discharge of mothers
postpartum has increased the ratio of false positive TSH elevations. Although
transient hypothyroidism may occur frequently, all these infants should be
treated as having CH for the first 3 years of life, taking into account the risk
of mental retardation. A reevaluation after 3 years is needed in such patients.
The goal of initial therapy in CH is to minimize neonatal central nervous system
exposure to hypothyroidism by normalizing thyroid function, as rapidly as
possible.
PMID- 23154159
TI - Subclinical hypothyroidism in children: natural history and when to treat.
AB - Subclinical hypothyroidism (SH) is a quite common disorder in the pediatric age
group. The aim of this paper is to present a review of the studies investigating
the natural course of SH and the effects of replacement therapy with
levothyroxine in childhood. We systematically searched PubMed, Cochrane, and
EMBASE (1990 to 2012) and identified 14 articles suitable to be included. SH is a
benign process that does not influence anthropometric parameters or puberty
onset, and in most cases, it is a remitting disease, with a low risk of
development of overt hypothyroidism, more frequently evolving toward euthyroidism
or steadily remaining in a condition of isolated hyperthyrotropinemia.Studies
analyzing the effects of replacement therapy in SH have reported an increased
growth velocity in children with short stature or chronic diseases, discordant
effects on thyroid volume reduction, and no effects on neurocognitive function.
SH in children and adolescent is often a self-remitting process and its treatment
should be considered only when thyroid stimulating hormone values are higher than
10 mIU/L,when clinical signs or symptoms of impaired thyroid function or goiter
are detected, or when SH is associated with other chronic diseases.
PMID- 23154161
TI - Hyperthyroidism in childhood: causes, when and how to treat.
AB - Graves' disease (GD) is the most common cause of hyperthyroidism in children.
This review gives an overview and update of management of GD. Antithyroid drugs
(ATD) are recommended as the initial treatment, but the major problem is the high
relapse rate (30%) as remission is achieved after a first course of ATD. More
prolonged medical treatment may increase the remission rate up to 50%.
Alternative treatments, such as radioactive iodine or thyroidectomy, are
considered in cases of relapse, lack of compliance, or ATD toxicity. Therefore,
clinicians have sought prognostic indicators of remission. Relapse risk decreases
with longer duration of the first course of ATD treatment, highlighting the
positive impact of a long period of primary ATD treatment on outcome. The
identification of other predictive factors such as severe biochemical
hyperthyroidism at diagnosis, young age, and absence of other autoimmune
conditions has made it possible to stratify patients according to the risk of
relapse after ATD treatment, leading to improvement in patient management by
facilitating the identification of patients requiring long-term ATD or early
alternative therapy. Neonatal autoimmune hyperthyroidism is generally transient,
occurring in only about 2% of the offspring of mothers with GD. Cardiac
insufficiency, intrauterine growth retardation, craniostenosis, microcephaly and
psychomotor disabilities are the major risks in these infants and highlight the
importance of thyroid hormone receptor antibody determination throughout
pregnancy in women with GD, as well as highlighting the need for early diagnosis
and treatment of hyperthyroidism.
PMID- 23154162
TI - Current loss-of-function mutations in the thyrotropin receptor gene: when to
investigate, clinical effects, and treatment.
AB - Thyroid-stimulating hormone receptor (TSHR) loss-of-function (LOF) mutations lead
to a wide spectrum of phenotypes, ranging from severe congenital hypothyroidism
(CH) to mild euthyroid hyperthyrotropinemia. The degree of TSH resistance depends
on the severity of the impairment of the receptor function caused by the mutation
and on the number of mutated alleles In this review data about genotype-phenotype
correlation and criteria for clinical work-up will be presented and discussed.
Complete TSH resistance due to biallelic LOF TSHR mutations must be suspected in
all patients with severe not syndromic CH and severe thyroid hypoplasia diagnosed
at birth by neonatal screening. Partial forms of TSH resistance show a more
heterogeneous hormonal and clinical pattern . In these cases TSH serum levels are
above the upper limit of normal range for the age but with a very variable
pattern, free thyroxine (T4) concentrations are within the normal range and
thyroid size can be normal or hypoplastic at ultrasound scan. An early
substitutive treatment with L-T4 must be mandatory in all patients with severe CH
due to complete uncompensated TSH resistance diagnosed at birth by neonatal
screening. The usefulness of substitutive treatment appears much more
controversial inpatients with subclinical hypothyroidism due to partial TSH
resistance in whom the increased TSH concentration should be able to compensate
the mild functional impairment of the mutant receptor. Together with standard
criteria we recommend also an accurate clinical work-up to select patients who
are candidates for a LOF TSHR mutation.
PMID- 23154163
TI - Optimising outcome in congenital hypothyroidism; current opinions on best
practice in initial assessment and subsequent management.
AB - Congenital hypothyroidism (CH), usually of the primary and permanent variety, is
an eminently preventable cause of growth retardation and mental handicap whose
outlook has been transformed by newborn screening, usually involving the
measurement of capillary thyroid stimulating hormone (TSH). Severe primary CH,
due for example to athyreosis, may result in subtle cognitive, behavioural and
sensori-motor deficits, but the extent to which these can be offset by optimal
postnatal diagnosis and management remains uncertain. This is because the
available adult follow-up data reflect the outcome of previous management in the
1970's and 1980's, and also because the accurate neuro-psychological assessment
of children is difficult, particularly in the preschool population. There is an
urgent need to develop new consensus guidelines and to ensure that the children
managed according to such guidelines are systematically and prospectively
assessed so that good quality outcome data become available. In this review, key
recommendations in the management of CH include: screening at day 3 so that
severely affected infants can begin treatment within the first 10 days of life;
setting the TSH referral cut-off at 8-10 mU/L; adopting a disciplined diagnostic
algorithm to evaluate referred cases, with measurement of venous free thyroxine
(T4), TSH and thyroglobulin combined with dual ultrasound and radioisotope
imaging; initial treatment with a T4 dose of 50 MUg daily in infants weighing >=
2.5 kg and 15 MUg/kg/day in infants weighing < 2.5 kg followed by weekly review
until thyroid function is normalised; and maintenance of free T4 levels between
15-26 pmol/L and TSH between 0.5-5 mU/L thereafter to avoid both under- and
overtreatment.
PMID- 23154164
TI - Autoimmune thyroiditis in childhood.
AB - Autoimmune thyroiditis (AIT) is the most common thyroid disorder in the pediatric
age range. The disease results from an as yet poorly characterized defect or
defects in immunoregulation and a cascade of events progressing from lymphocyte
infiltration of the thyroid, to T-cell- and cytokine-mediated thyroid follicular
cell injury, and apoptotic cell death. Approximately 70% of disease risk has been
attributed to genetic background with environmental factors being important in
triggering disease in susceptible individuals. The contribution of individual
genes is small and probably polymorphisms in multiple genes play a role. Some
immuno susceptibility genes affect immune recognition or response in general,
while others are thyroid-specific. Environmental agents may act through an
epigenetic mechanism. Antibodies (Abs) to a variety of thyroid-specific antigens
are detectable in a majority of patients, but the role of Abs in mediating cell
injury and death is unclear and only thyrotropin (TSH) receptor Abs significantly
affect thyroid function by interfering with (or stimulating) the action of TSH.
Nonetheless, thyroid peroxidase (TPO) Abs and thyroglobulin (Tg) Abs, present in
a majority of patients, are valuable diagnostically as markers of underlying
autoimmune thyroid destruction. TSH receptor blocking Abs are found in ~18% of
children and adolescents with severe hypothyroidism and, when persistent, may
identify an adolescent likely to have a baby with TSH receptor blocking Ab
induced congenital hypothyroidism. AIT may coexist with other organ-specific
autoimmune diseases. Although the most common age at presentation is adolescence,
the disease may occur rarely in children <1 year of life.
PMID- 23154165
TI - C-terminal turn stability determines assembly differences between Abeta40 and
Abeta42.
AB - Oligomerization of the amyloid beta-protein (Abeta) is a seminal event in
Alzheimer's disease. Abeta42, which is only two amino acids longer than Abeta40,
is particularly pathogenic. Why this is so has not been elucidated fully. We
report here results of computational and experimental studies revealing a C
terminal turn at Val36-Gly37 in Abeta42 that is not present in Abeta40. The
dihedral angles of residues 36 and 37 in an Ile31-Ala42 peptide were consistent
with beta-turns, and a beta-hairpin-like structure was indeed observed that was
stabilized by hydrogen bonds and by hydrophobic interactions between residues 31
35 and residues 38-42. In contrast, Abeta(31-40) mainly existed as a statistical
coil. To study the system experimentally, we chemically synthesized Abeta
peptides containing amino acid substitutions designed to stabilize or destabilize
the hairpin. The triple substitution Gly33Val-Val36Pro-Gly38Val ("VPV")
facilitated Abeta42 hexamer and nonamer formation, while inhibiting formation of
classical amyloid-type fibrils. These assemblies were as toxic as were assemblies
from wild-type Abeta42. When substituted into Abeta40, the VPV substitution
caused the peptide to oligomerize similarly to Abeta42. The modified Abeta40 was
significantly more toxic than Abeta40. The double substitution d-Pro36-l-Pro37
abolished hexamer and dodecamer formation by Abeta42 and produced an oligomer
size distribution similar to that of Abeta40. Our data suggest that the Val36
Gly37 turn could be the sine qua non of Abeta42. If true, this structure would be
an exceptionally important therapeutic target.
PMID- 23154166
TI - Amyloid formation in heterogeneous environments: islet amyloid polypeptide
glycosaminoglycan interactions.
AB - Amyloid formation plays an important role in a broad range of diseases, and the
search for amyloid inhibitors is an active area of research. Amyloid formation
takes places in a heterogeneous environment in vivo with the potential for
interactions with membranes and with components of the extracellular matrix.
Naturally occurring amyloid deposits are associated with sulfated proteoglycans
and other factors. However, the vast majority of in vitro assays of amyloid
formation and amyloid inhibition are conducted in homogeneous solution where the
potential for interactions with membranes or sulfated proteoglycans is lacking
and it is possible that different results may be obtained in heterogeneous
environments. We show that variants of islet amyloid polypeptide (IAPP), which
are non-amyloidogenic in homogeneous solution, can be readily induced to form
amyloid in the presence of glycosaminoglycans (GAGs). GAGs are found to be more
effective than anionic lipid vesicles at inducing amyloid formation on a per
charge basis. Several known inhibitors of IAPP amyloid formation are shown to be
less effective in the presence of GAGs.
PMID- 23154167
TI - Native-state heterogeneity of beta(2)-microglobulin as revealed by kinetic
folding and real-time NMR experiments.
AB - The kinetic folding of beta(2)-microglobulin from the acid-denatured state was
investigated by interrupted-unfolding and interrupted-refolding experiments using
stopped-flow double-jump techniques. In the interrupted unfolding, we first
unfolded the protein by a pH jump from pH7.5 to pH2.0, and the kinetic refolding
assay was carried out by the reverse pH jump by monitoring tryptophan
fluorescence. Similarly, in the interrupted refolding, we first refolded the
protein by a pH jump from pH2.0 to pH7.5 and used a guanidine hydrochloride
(GdnHCl) concentration jump as well as the reverse pH jump as unfolding assays.
Based on these experiments, the folding is represented by a parallel-pathway
model, in which the molecule with the correct Pro32 cis isomer refolds rapidly
with a rate constant of 5-6 s(-1), while the molecule with the Pro32 trans isomer
refolds more slowly (pH7.5 and 25 degrees C). At the last step of folding, the
native-like trans conformer produced on the latter pathway isomerizes very slowly
(0.001-0.002 s(-1)) into the native cis conformer. In the GdnHCl-induced
unfolding assays in the interrupted refolding, the native-like trans conformer
unfolded remarkably faster than the native cis conformer, and the direct GdnHCl
induced unfolding was also biphasic, indicating that the native-like trans
conformer is populated at a significant level under the native condition. The one
dimensional NMR and the real-time NMR experiments of refolding further indicated
that the population of the trans conformer increases up to 7-9% under a more
physiological condition (pH7.5 and 37 degrees C).
PMID- 23154168
TI - Conformational analysis of StrH, the surface-attached exo-beta-D-N
acetylglucosaminidase from Streptococcus pneumoniae.
AB - Streptococcus pneumoniae is a serious human pathogen that presents on its surface
numerous proteins involved in the host-bacterium interaction. The carbohydrate
active enzymes are particularly well represented among these surface proteins,
and many of these are known virulence factors, highlighting the importance of
carbohydrate processing by this pathogen. StrH is a surface-attached exo-beta-D-N
acetylglucosaminidase that cooperates with the sialidase NanA and the beta
galactosidase BgaA to sequentially degrade the nonreducing terminal arms of
complex N-linked glycans. This enzyme is a large multi-modular protein that is
notable for its tandem N-terminal family GH20 catalytic modules, whose individual
X-ray crystal structures were recently reported. StrH also contains C-terminal
tandem G5 modules, which are uncharacterized. Here, we report the NMR-determined
solution structure of the first G5 module in the tandem, G5-1, which along with
the X-ray crystal structures of the GH20 modules was used in conjunction with
small-angle X-ray scattering to construct a pseudo-atomic model of full-length
StrH. The results reveal a model in which StrH adopts an elongated conformation
that may project the catalytic modules away from the surface of the bacterium to
a distance of up to ~250 A.
PMID- 23154169
TI - Structure-based redesign of the binding specificity of anti-apoptotic Bcl-x(L).
AB - Many native proteins are multi-specific and interact with numerous partners,
which can confound analysis of their functions. Protein design provides a
potential route to generating synthetic variants of native proteins with more
selective binding profiles. Redesigned proteins could be used as research tools,
diagnostics or therapeutics. In this work, we used a library screening approach
to reengineer the multi-specific anti-apoptotic protein Bcl-x(L) to remove its
interactions with many of its binding partners, making it a high-affinity and
selective binder of the BH3 region of pro-apoptotic protein Bad. To overcome the
enormity of the potential Bcl-x(L) sequence space, we developed and applied a
computational/experimental framework that used protein structure information to
generate focused combinatorial libraries. Sequence features were identified using
structure-based modeling, and an optimization algorithm based on integer
programming was used to select degenerate codons that maximally covered these
features. A constraint on library size was used to ensure thorough sampling.
Using yeast surface display to screen a designed library of Bcl-x(L) variants, we
successfully identified a protein with ~1000-fold improvement in binding
specificity for the BH3 region of Bad over the BH3 region of Bim. Although
negative design was targeted only against the BH3 region of Bim, the best
redesigned protein was globally specific against binding to 10 other peptides
corresponding to native BH3 motifs. Our design framework demonstrates an
efficient route to highly specific protein binders and may readily be adapted for
application to other design problems.
PMID- 23154170
TI - Structural and biophysical characterization of the Syk activation switch.
AB - Syk is an essential non-receptor tyrosine kinase in intracellular immunological
signaling, and the control of Syk kinase function is considered as a valuable
target for pharmacological intervention in autoimmune or inflammation diseases.
Upon immune receptor stimulation, the kinase activity of Syk is regulated by
binding of phosphorylated immune receptor tyrosine-based activating motifs
(pITAMs) to the N-terminal tandem Src homology 2 (tSH2) domain and by
autophosphorylation with consequences for the molecular structure of the Syk
protein. Here, we present the first crystal structures of full-length Syk (fl
Syk) as wild type and as Y348F,Y352F mutant forms in complex with AMP-PNP
revealing an autoinhibited conformation. The comparison with the crystal
structure of the truncated Syk kinase domain in complex with AMP-PNP taken
together with ligand binding studies by surface plasmon resonance (SPR) suggests
conformational differences in the ATP sites of autoinhibited and activated Syk
forms. This hypothesis was corroborated by studying the thermodynamic and kinetic
interaction of three published Syk inhibitors with isothermal titration
calorimetry and SPR, respectively. We further demonstrate the modulation of
inhibitor binding affinities in the presence of pITAM and discuss the observed
differences of thermodynamic and kinetic signatures. The functional relevance of
pITAM binding to fl-Syk was confirmed by a strong stimulation of in vitro
autophosphorylation. A structural feedback mechanism on the kinase domain upon
pITAM binding to the tSH2 domain is discussed in analogy of the related family
kinase ZAP-70 (Zeta-chain-associated protein kinase 70). Surprisingly, we
observed distinct conformations of the tSH2 domain and the activation switch
including Tyr348 and Tyr352 in the interdomain linker of Syk in comparison to ZAP
70.
PMID- 23154171
TI - The molten globule of beta(2)-microglobulin accumulated at pH 4 and its role in
protein folding.
AB - The acid transition of beta(2)-microglobulin (beta2m) was studied by tryptophan
fluorescence, peptide circular dichroism, and NMR spectroscopy. The protein
exhibits a three-state transition with an equilibrium intermediate accumulated at
pH4 (25 degrees C). The pH4 intermediate has typical characteristics of the
molten globule (MG) state; it showed a native-like secondary structure without
specific side-chain tertiary structure, and the hydrodynamic radius determined by
pulse field gradient NMR was only 20% larger than that of the native state. The
accumulation of the pH4 intermediate is very analogous to the behavior of
apomyoglobin, for which the pH4 MG has been well characterized, although beta2m,
a beta-protein, is structurally very different from alpha-helical apomyoglobin.
NMR pH titration of histidine residues of beta2m has also indicated that His84
has an abnormally low pK(a) value in the native state. From the pH dependence of
the unfolding transition, the protonations of this histidine and 10 weakly
abnormal carboxylates triggered the transition from the native to the MG state.
This behavior is again analogous to that of apomyoglobin, suggesting a common
mechanism of production of the pH4 MG. In contrast to the folding of
apomyoglobin, in which the MG was equivalent to the burst-phase kinetic folding
intermediate, the burst-phase refolding intermediate of beta2m, detected by
stopped-flow circular dichroism, was significantly more structured than the pH4
intermediate. It is proposed that the folding of beta2m from its acid-denatured
state takes place in the following order: denatured state->MG->burst-phase
intermediate->native state.
PMID- 23154173
TI - [New in the medical press?].
PMID- 23154174
TI - Quantitative bone ultrasound in pediatric patients with cystic fibrosis.
PMID- 23154175
TI - Standardized outpatient management of Klebsiella pneumoniae liver abscesses.
AB - OBJECTIVES: Community-acquired Klebsiella pneumoniae has emerged as a major cause
of liver abscess in Asia. Using a standardized protocol, we conducted a
prospective cohort study of all cases of K. pneumoniae liver abscess treated from
2005 to 2011 at two outpatient parenteral antimicrobial therapy (OPAT) centers in
Singapore, to assess the safety and efficacy of treatment. METHODS: We included
all OPAT eligible patients with radiologically confirmed (computed tomography or
ultrasound) liver abscesses and K. pneumoniae-positive microbiological cultures
obtained from abscess fluid and/or blood at two university teaching hospitals.
The endpoints investigated were cure, clinical response, readmission, and
mortality. RESULTS: All 109 patients enrolled in the study successfully completed
treatment in OPAT. Nine patients required a short-term readmission due to
clinical deterioration. There were no deaths or relapses at 30 days post
cessation of antibiotics. Abscess size greater than 5 cm was associated with a
delayed clinical response (odds ratio 5.34, 95% confidence interval 1.25-22.91, p
= 0.02). CONCLUSION: The management of K. pneumoniae liver abscesses via OPAT
using a standardized protocol is a safe and effective alternative to inpatient
intravenous antibiotics.
PMID- 23154176
TI - Is hepatitis B virus transmitted via the male germ line? A seroepidemiological
study in fetuses.
AB - OBJECTIVES: To detect father-to-fetus transmission of hepatitis B virus (HBV) in
utero. METHODS: We conducted a study at the prenatal diagnosis center of Taizhou
City. Fetuses with one or both parents carrying the hepatitis B surface antigen
(HBsAg) were identified before genetic testing during the period 2008-2010.
Intrauterine samples were obtained by amniocentesis or cordocentesis and tested
for serological markers and by quantitative DNA assays. All neonates received
combined hepatitis B immunoprophylaxis after delivery, and serological follow-up
tests were performed at 1 year of age. RESULTS: Of the 407 couples enrolled in
the study, HBV was carried by fathers only in 164, and none of their fetuses were
found to be HBV DNA-positive in utero. All fetal serological markers were found
to be of maternal but not paternal origin. The response rate to postnatal
vaccination was 98.6%, and none of the children who failed immunoprophylaxis were
the offspring of the HBV carrier fathers. CONCLUSIONS: The infection of fetuses
with HBV from the spermatozoa of carrier fathers seems unlikely, especially in an
area where pre-conception hepatitis B vaccination is routinely provided.
PMID- 23154177
TI - Impact evaluation of a sexually transmitted disease preventive intervention among
female sex workers in Hohhot, China.
AB - OBJECTIVES: The aim of this study was to evaluate the impact of HIV and sexually
transmitted disease (STD) prevention interventions among female sex workers
(FSWs) in the city of Hohhot in northern China. METHODS: Three serial cross
sectional surveys were conducted in 2006, 2007, and 2008 among FSWs. A
questionnaire was administered to the FSWs, and HIV and syphilis tests were
performed for all participants. Intervention activities including condom
promotion and provision, increased condom availability and accessibility, and
voluntary HIV counseling and testing (VCT) were carried out among FSWs. RESULTS:
There were 624 participants in the 2006 survey, 444 in the 2007 survey, and 451
in the 2008 survey. The United Nations General Assembly Special Session (UNGASS)
indicators for FSWs increased from 13.9% in 2006 to 37.7% in 2008 (p<0.001). The
average rate of consistent condom use with commercial clients in the month
preceding the interview increased significantly from 39.8% in 2006 to 59.6% in
2008 (p<0.001). Not a single HIV-positive case was found among the FSWs over
these 3 years, and the prevalence of syphilis decreased remarkably from 9.5% in
2006 to 1.3% in 2008. Logistic regression analysis showed that sauna or hair
salon work venues, receiving services from intervention programs, and accepting
HIV tests were factors associated with consistent condom use. CONCLUSIONS: The
findings suggest that consistent condom use and awareness of HIV/AIDS prevention
related knowledge among FSWs have been improved by the intervention. Further
prioritized and combined prevention programs aimed at FSWs are needed in order to
prevent the HIV/AIDS epidemic spreading in the general population in China.
PMID- 23154178
TI - Initial characterization of a dually radiolabeled peptide for simultaneous
monitoring of protein targets and enzymatic activity.
AB - OBJECTIVE: The goal of this study was to develop dually radiolabeled peptides for
simultaneous imaging of cancer cell localization by targeting the alpha(v)beta(3)
integrin and their pathophysiology by targeting the activity of the proteolytic
enzyme MMP2, involved in the metastatic process. METHODS: A hybrid peptide
c(RGDfE)K(DOTA)PLGVRY containing an RGD motif for binding to the
alpha(v)beta(3)integrin, a metal chelator (DOTA) for radiolabeling with [(64)Cu],
and the MMP2 substrate cleavage sequence PLGVRY with terminal tyrosine for
labeling with [(123)I] was synthesized, labeled with [(64)Cu] and [(123)I], and
evaluated in vitro as a potential imaging agent. RESULTS: The peptide was
synthesized and labeled with [(64)Cu] and [(123)I] with 300 and 40 MUCi/MUg (542
and 72.2 mCi/MUmol) specific activities, respectively, and radiochemical purity
of >98%. c(RGDfE)K(DOTA)PLGVRY demonstrated high affinity for alpha(v)beta(3)
integrins (Kd=83.4+13.2 nM) in both substrate competition and cell binding
assays. c(RGDfE)K(DOTA)PLGVRY peptide, but not the scrambled version,
c(RGDfE)K(DOTA)GRPLVY was specifically cleaved by MMP2. CONCLUSIONS: These
results demonstrate the feasibility of developing dually radiolabeled peptides
for the simultaneous imaging of cancer cells and their pathophysiologic activity.
PMID- 23154180
TI - Simvastatin inhibits the core promoter of the TXNRD1 gene and lowers cellular
TrxR activity in HepG2 cells.
AB - Thioredoxin reductase 1 (TrxR1) is a selenocysteine-containing redox-active
enzyme that is thought to be important during carcinogenesis. We have recently
shown that treatment with statins, HMGCoA reductase inhibitors, reduces the
levels of TrxR1 in liver of both rat and human. The reduced TrxR1 levels were
correlated with inhibited hepatocarcinogenesis in a rat model. The aim of the
present study was to investigate if statins affect the activity of the human
TXNRD1 core promoter, which guides expression of TrxR1, and if the effects by
statins on TrxR1 expression in liver could be reproduced in a cellular model
system. We found that simvastatin and fluvastatin decreased cellular TrxR
activity in cultured human liver-derived HepG2 cells with approximately 40%
(p<0.05). Simvastatin, but not fluvastatin or atorvastatin, also reduced the
TXNRD1 promoter activity in HepG2 cells by 20% (p<0.01). In line with this
result, TrxR1 mRNA levels decreased with about 25% in non-transfected HepG2 cells
upon treatment with simvastatin (p<0.01). Concomitant treatment with mevalonate
could not reverse these effects of simvastatin, indicating that other mechanisms
than HMGCoA reductase inhibition was involved. Also, simvastatin did not inhibit
sulforaphane-derived stimulation of the TXNRD1 core promoter activity, suggesting
that the inhibition by simvastatin was specific for basal and not Nrf2-activated
TrxR1 expression. In contrast to simvastatin, the two other statins tested,
atorvastatin or fluvastatin, did not influence the TrxR1 mRNA levels. Thus, our
results reveal a simvastatin-specific reduction of cellular TrxR1 levels that at
least in part involves direct inhibitory effects on the basal activity of the
core promoter guiding TrxR1 expression.
PMID- 23154179
TI - In vivo evidence that Agxt2 can regulate plasma levels of dimethylarginines in
mice.
AB - Elevated plasma concentrations of the asymmetric (ADMA) and symmetric (SDMA)
dimethylarginine have repeatedly been linked to adverse cardiovascular clinical
outcomes. Both dimethylarginines can be degraded by alanine-glyoxylate
aminotransferase 2 (Agxt2), which is also the key enzyme responsible for the
degradation of endogenously formed beta-aminoisobutyrate (BAIB). In the present
study we wanted to investigate the effect of BAIB on Agxt2 expression and Agxt2
mediated metabolism of dimethylarginines. We infused BAIB or saline
intraperitoneally for 7days in C57/BL6 mice via minipumps. Expression of Agxt2
was determined in liver and kidney. The concentrations of BAIB, dimethylarginines
and the Agxt2-specific ADMA metabolite alpha-keto-delta-(N(G),N(G)
dimethylguanidino)valeric acid (DMGV) was determined by LC-MS/MS in plasma and
urine. As compared to controls systemic administration of BAIB increased plasma
and urine BAIB levels by a factor of 26.5 (p<0.001) and 25.8 (p<0.01),
respectively. BAIB infusion resulted in an increase of the plasma ADMA and SDMA
concentrations of 27% and 31%, respectively, (both p<0.05) and a 24% decrease of
plasma DMGV levels (p<0.05), while expression of Agxt2 was not different. Our
data demonstrate that BAIB can inhibit Agxt2-mediated metabolism of
dimethylarginines and show for the first time that endogenous Agxt2 is involved
in the regulation of systemic ADMA, SDMA and DMGV levels. The effect of BAIB
excess on endogenous dimethylarginine levels may have direct clinical
implications for humans with the relatively common genetic trait of hyper-beta
aminoisobutyric aciduria.
PMID- 23154181
TI - SnoN/SKIL modulates proliferation through control of hsa-miR-720 transcription in
esophageal cancer cells.
AB - It is now evident that changes in microRNA are involved in cancer progression,
but the mechanisms of transcriptional regulation of miRNAs remain unknown. Ski
related novel gene (SnoN/SKIL), a transcription co-factor, acts as a potential
key regulator within a complex network of p53 transcriptional repressors. SnoN
has pro- and anti-oncogenic functions in the regulation of cell proliferation,
senescence, apoptosis, and differentiation. We characterized the roles of SnoN in
miRNA transcriptional regulation and its effects on cell proliferation using
esophageal squamous cell carcinoma (ESCC) cells. Silencing of SnoN altered a set
of miRNA expression profiles in TE-1cells, and the expression levels of miR-720,
miR-1274A, and miR-1274B were modulated by SnoN. The expression of these miRNAs
resulted in changes to the target protein p63 and a disintegrin and
metalloproteinase domain 9 (ADAM9). Furthermore, silencing of SnoN significantly
upregulated cell proliferation in TE-1 cells, indicating a potential anti
oncogenic function. These results support our observation that cancer tissues
have lower expression levels of SnoN, miR-720, and miR-1274A compared to adjacent
normal tissues from ESCC patients. These data demonstrate a novel mechanism of
miRNA regulation, leading to changes in cell proliferation.
PMID- 23154182
TI - IL-35 over-expression increases apoptosis sensitivity and suppresses cell growth
in human cancer cells.
AB - Interleukin (IL)-35 is a novel heterodimeric cytokine in the IL-12 family and is
composed of two subunits: Epstein-Barr virus-induced gene 3 (EBI3) and IL-12p35.
IL-35 is expressed in T regulatory (Treg) cells and contributes to the immune
suppression function of these cells. In contrast, we found that both IL-35
subunits were expressed concurrently in most human cancer cell lines compared to
normal cell lines. In addition, we found that TNF-alpha and IFN-gamma stimulation
led to increased IL-35 expression in human cancer cells. Furthermore, over
expression of IL-35 in human cancer cells suppressed cell growth in vitro,
induced cell cycle arrest at the G1 phase, and mediated robust apoptosis induced
by serum starvation, TNF-alpha, and IFN-gamma stimulation through the up
regulation of Fas and concurrent down-regulation of cyclinD1, survivin, and Bcl-2
expression. In conclusion, our results reveal a novel functional role for IL-35
in suppressing cancer activity, inhibiting cancer cell growth, and increasing the
apoptosis sensitivity of human cancer cells through the regulation of genes
related to the cell cycle and apoptosis. Thus, this research provides new
insights into IL-35 function and presents a possible target for the development
of novel cancer therapies.
PMID- 23154183
TI - Regulation of cooperative function of the Il12b enhancer and promoter by the
interferon regulatory factors 3 and 5.
AB - The regulation of the Il12b gene, encoding the shared p40 subcomponent for IL-12
and IL-23, is critical for innate immune responses and subsequent T cell
polarization. This gene is robustly induced upon Toll-like receptor (TLR)
stimulation, wherein an enhancer located 10kb upstream of the transcription start
site is required for promoter activity; however, the underlying mechanisms that
regulate this enhancer in cooperation with the promoter has remained elusive. We
show here that the Il12b enhancer contains functional ISREs for recognition by
interferon regulatory factors (IRFs), and provide evidence that TLR-activated
IRF5 mediates cooperativity of the enhancer with the promoter which also contains
ISREs. By contrast, IRF3 activated by cytosolic RIG-I-like receptor (RLR)
signaling binds to these ISREs and causes gene suppression. Consistently, IRF5
binding is accompanied with chromatin remodeling of both regulatory regions and
the formation of a productive transcriptional complex containing other
transcription factors, whereas these events are inhibited by IRF3 binding. We
show that the ISREs embedded in the enhancer are indeed critical for its
activation by IRF5. We also adduce evidence that the 5' sequences of the enhancer
and promoter ISREs, all of which deviate from consensus ISREs, critically affect
the function of IRF3. The dual commitment of these IRFs in the regulation of the
Il12b enhancer and promoter is unique and may have implications for understanding
the evolution of this gene.
PMID- 23154184
TI - Effect of taurine and N-acetylcysteine on methionine restriction-mediated
adiposity resistance.
AB - OBJECTIVES: Methionine-restricted (MR) rats, which are lean and insulin
sensitive, have low serum total cysteine (tCys) and taurine and decreased hepatic
expression and activity indices of stearoyl-coenzyme A desaturase-1 (SCD1). These
effects are partly or completely reversed by cysteine supplementation. We
investigated whether reversal of MR phenotypes can be achieved by other sulfur
compounds, namely taurine or N-acetylcysteine (NAC). METHODS: MR and control-fed
(CF) rats were supplemented with taurine (0.5%) or NAC (0.5%) for 12weeks.
Adiposity, serum sulfur amino acids (SAA), Scd1 gene expression in liver and
white adipose tissue, and SCD1 activity indices (calculated from serum fatty acid
profile) were monitored. RESULTS: Taurine supplementation of MR rats did not
restore weight gain or hepatic Scd1 expression or indices to CF levels, but
further decreased adiposity. Taurine supplementation of CF rats did not affect
adiposity, but lowered triglyceridemia. NAC supplementation in MR rats raised
tCys and partly or completely reversed MR effects on weight, fat %, Scd1
expression in liver and white adipose tissue, and estimated SCD1 activity. In CF
rats, NAC decreased body fat % and lowered SCD1-18 activity index (P<0.001).
Serum triglycerides and leptin were over 40% lower in CF+NAC relative to CF rats
(P<=0.003 for both). In all groups, change in tCys correlated with change in SCD1
16 index (partial r=0.60, P<0.001) independent of other SAA. CONCLUSION: The
results rule out taurine as a mediator of increased adiposity produced by
cysteine in MR, and show that NAC, similar to L-cysteine, blocks anti-obesity
effects of MR. Our data show that dietary SAA can influence adiposity in part
through mechanisms that converge on SCD1 function. This may have implications for
understanding and preventing human obesity.
PMID- 23154185
TI - Zinc and pregnancy: Marked changes on the immune response following zinc therapy
for pregnant females challenged with Trypanosoma cruzi.
AB - BACKGROUND & AIMS: The occurrence of infectious disease processes during
pregnancy has significant effects on maternal health and can lead to adverse
pregnancy outcomes. The aim of the present study was to examine the potential
role of zinc treatment during Trypanosoma cruzi infection in pregnant animals.
METHODS: Female Wistar rats weighing 180-200 g were used in all experiments.
Production of nitric oxide, peritoneal macrophages counts, and concentrations of
IFN-gamma and TNF-alpha were measured, and the potential protective effects of
zinc on fetal development were assessed at 14-day post-infection. RESULTS: Nitric
oxide concentrations were higher in pregnant zinc-treated animals than in their
untreated counterparts, despite similar levels of the macrophages, IFN-gamma and
TNF-alpha. Zinc therapy was associated with a significant reduction in
parasitemia and cardiac parasite burden. Higher placental and birth weights were
observed in animals given prenatal zinc supplementation compared to untreated
animals. CONCLUSIONS: These data confirm the critical importance of adequate zinc
intake during the peri-conceptional period and indicate that zinc has an
effective role in preventing adverse outcomes of pregnancy and reducing the risk
of common infections such as Chagas' disease.
PMID- 23154186
TI - Subthreshold vestibular reflex effects in seated humans can contribute to soleus
activation when combined with cutaneous inputs.
AB - The integration of vestibular and somatosensory information for the control of
lower limb musculature remains elusive. To determine whether a subthreshold
vestibular input influences the cutaneous evoked response, the isometric EMG
activity in the posturally inactive soleus muscles of 13 healthy, seated subjects
was collected. Vestibular afferents were activated using galvanic vestibular
stimulation (GVS; 1.8-2.5mA, 500ms), while percutaneous electrical stimulation
was delivered to the distal tibial nerve (11ms train of 3 * 1.0 ms pulses, 200Hz)
to activate foot sole skin afferents. GVS elicited responses in soleus both
independently and when combined with cutaneous stimulation. The responses to the
combined sensory input showed an interaction between the two sensory modalities
to influence muscle activation. Of note is the presence of significant muscle
modulation in the combined condition, where subthreshold vestibular inputs
altered the outcome of the cutaneous reflex response. This finding has
implications for individuals with sensory deficiency. In the case of an absent or
deficient sensory modality, balance protective reflexes to maintain postural
equilibrium may be enhanced with targeted sensory augmentation.
PMID- 23154187
TI - Behavior of the magnetization in spin-locking magnetic resonance imaging using
numerical solutions to the time-dependent Bloch equations.
AB - We present a simple method for calculating the magnetization in spin-locking (SL)
magnetic resonance imaging (MRI), in which a simple matrix equation was derived
for solving the time-dependent Bloch equations in the 2-pool chemical exchange
model. We also present a method for visualizing the trajectory of a magnetization
vector in a three-dimensional (3D) space. The longitudinal relaxation time in the
rotating frame (T(1rho)) was calculated by fitting the z component of
magnetization for a duration of SL (t(SL)) (M(z)(t(SL))) to M(z)(t(SL)) = (M(0) -
M(zss))exp ( - t(SL)/T(1rho)) + M(zss), where M(0) and M(z)(ss) denote the
thermal equilibrium and steady-state z component of magnetization, respectively,
and was compared with that calculated from the solution given by Trott and
Palmer. Our 3D plots clearly visualized the effect of SL. When the population of
the two pools was highly asymmetric, there was good agreement between the T(1rho)
values obtained by our method and Trott and Palmer's solutions. The difference
between them increased with decreasing asymmetry in the population of the two
pools. Our method will be useful for better understanding and optimization of SL
MRI, because it allows us to calculate the magnetization vector and to visualize
its trajectory simply and quickly.
PMID- 23154188
TI - Protein space: a natural method for realizing the nature of protein universe.
AB - Current methods cannot tell us what the nature of the protein universe is
concretely. They are based on different models of amino acid substitution and
multiple sequence alignment which is an NP-hard problem and requires manual
intervention. Protein structural analysis also gives a direction for mapping the
protein universe. Unfortunately, now only a minuscule fraction of proteins' 3
dimensional structures are known. Furthermore, the phylogenetic tree
representations are not unique for any existing tree construction methods. Here
we develop a novel method to realize the nature of protein universe. We show the
protein universe can be realized as a protein space in 60-dimensional Euclidean
space using a distance based on a normalized distribution of amino acids. Every
protein is in one-to-one correspondence with a point in protein space, where
proteins with similar properties stay close together. Thus the distance between
two points in protein space represents the biological distance of the
corresponding two proteins. We also propose a natural graphical representation
for inferring phylogenies. The representation is natural and unique based on the
biological distances of proteins in protein space. This will solve the
fundamental question of how proteins are distributed in the protein universe.
PMID- 23154189
TI - A metapopulation model for chikungunya including populations mobility on a large
scale network.
AB - In this paper we study the influence of populations mobility on the spread of a
vector-borne disease. We focus on the chikungunya epidemic event that occurred in
2005-2006 on the Reunion Island, Indian Ocean, France, and validate our models
with real epidemic data from the event. We propose a metapopulation model to
represent both a high-resolution patch model of the island with realistic
population densities and also mobility models for humans (based on real-motion
data) and mosquitoes. In this metapopulation network, two models are coupled: one
for the dynamics of the mosquito population and one for the transmission of the
disease. A high-resolution numerical model is created from real geographical,
demographical and mobility data. The Island is modeled with an 18,000-nodes
metapopulation network. Numerical results show the impact of the geographical
environment and populations' mobility on the spread of the disease. The model is
finally validated against real epidemic data from the Reunion event.
PMID- 23154190
TI - Mathematical modeling of insulin secretion and the role of glucose-dependent
mobilization, docking, priming and fusion of insulin granules.
AB - In this paper we develop a new mathematical model of glucose-induced insulin
secretion from pancreatic islet beta-cells, and we use this model to investigate
the rate limiting factors. We assume that insulin granules reside in different
pools inside each beta-cell, and that all beta-cells respond homogeneously to
glucose with the same recruitment thresholds. Consistent with recent experimental
observations, our model also accounts for the fusion of newcomer granules that
are not pre-docked at the plasma membrane. In response to a single step increase
in glucose concentration, our model reproduces the characteristic biphasic
insulin release observed in multiple experimental systems, including perfused
pancreata and isolated islets of rodent or human origin. From our model analysis
we note that first-phase insulin secretion depends on rapid depletion of the
primed, release-ready granule pools, while the second phase relies on granule
mobilization from the reserve. Moreover, newcomers have the potential to
contribute significantly to the second phase. When the glucose protocol consists
of multiple changes in sequence (a so-called glucose staircase), our model
predicts insulin spikes of increasing height, as has been seen experimentally.
This increase stems from the glucose-dependent increase in the fusion rate of
insulin granules at the plasma membrane of single beta-cells. In contrast,
previous mathematical models reproduced the staircase experiment by assuming
heterogeneous beta-cell activation. In light of experimental data indicating
limited heterogeneous activation for beta-cells within intact islets, our
findings suggest that a graded, dose-dependent cell response to glucose may
contribute to insulin secretion patterns observed in multiple experiments, and
thus regulate in vivo insulin release. In addition, the strength of insulin
granule mobilization, priming and fusion are critical limiting factors in
determining the total amount of insulin release.
PMID- 23154191
TI - The effect of Fe-coverage on the structure, morphology and magnetic properties of
alpha-FeSi2 nanoislands.
AB - Self-assembled alpha-FeSi(2) nanoislands were formed using solid-phase epitaxy of
low (~1.2 ML) and high (~21 ML) Fe coverages onto vicinal Si(111) surfaces
followed by thermal annealing. At a resulting low Fe-covered Si(111) surface, we
observed in situ, by real-time scanning tunneling microscopy and surface electron
diffraction, the entire sequence of Fe-silicide formation and transformation from
the initially two-dimensional (2 * 2)-reconstructed layer at 300 degrees C into
(2 * 2)-reconstructed nanoislands decorating the vicinal step-bunch edges in a
self-ordered fashion at higher temperatures. In contrast, the silicide
nanoislands at a high Fe-covered surface were noticeably larger, more three
dimensional, and randomly distributed all over the surface. Ex situ x-ray
photoelectron spectroscopy and high-resolution transmission electron microscopy
indicated the formation of an alpha-FeSi(2) island phase, in an alpha
FeSi(2){112} // Si{111} orientation. Superconducting quantum interference device
magnetometry showed considerable superparamagnetism, with ~1.9 MU(B)/Fe atom at 4
K for the low Fe-coverage, indicating stronger ferromagnetic coupling of
individual magnetic moments, as compared to high Fe-coverage, where the
calculated moments were only ~0.8 MU(B)/Fe atom. Such anomalous magnetic
behavior, particularly for the low Fe-coverage case, is radically different from
the non-magnetic bulk alpha-FeSi(2) phase, and may open new pathways to high
density magnetic memory storage devices.
PMID- 23154192
TI - The impact of breastfeeding on FTO-related BMI growth trajectories: an
application to the Raine pregnancy cohort study.
AB - INTRODUCTION: For years, body mass index (BMI) has been used by scientists to
track weight problems and obesity in children and adults. Recent studies have
implicated the fat mass and obesity gene (FTO) in the increase of BMI in young
adults. A longer duration of breastfeeding is known to reduce the risk of being
overweight later in life, but its ability to modify the effect because of FTO is
not known. METHODS: We studied 1096 children from the Western Australian
Pregnancy (Raine) cohort who were followed up from birth to 14 years of age.
Linear mixed-effects models were used to investigate BMI growth trajectories in
boys and girls separately. RESULTS: An association was found between BMI growth
and the duration of exclusive breastfeeding (EXBF) among carriers of the risk
allele of the FTO SNP rs9939609. In girls, EXBF interacts with the SNP at
baseline and can reverse the increase in BMI because of SNP risk allele by age 14
years after 3 months of EXBF. In boys, EXBF reduces BMI both in carriers and non
carriers of the risk allele with an association found after 10 years of age. Six
months of EXBF will put the boys' BMI growth curves back to the normal range.
CONCLUSIONS: Our study could have major health implications by providing new
perspectives for the prevention of growth problems in children carrying risk
alleles in the FTO gene.
PMID- 23154194
TI - Amino acid derivatives as transdermal permeation enhancers.
AB - Transdermal permeation enhancers are compounds that temporarily decrease skin
barrier properties to promote drug flux. In this study, we investigated enhancers
with amino acids (proline, sarcosine, alanine, beta-alanine, and glycine)
attached to hydrophobic chain(s) via a biodegradable ester link. The double-chain
lipid-like substances displayed no enhancing effect, whereas single-chain
substances significantly increased skin permeability. The proline derivative l
Pro2 reached enhancement ratios of up to 40 at 1% concentration, which is higher
than that of the well-established and standard enhancers Azone, DDAIP, DDAK, and
Transkarbam 12. No stereoselectivity was observed. l-Pro2 acted synergistically
with propylene glycol. Infrared studies revealed that l-Pro2 forms a separate
liquid ordered phase in the stratum corneum lipids and has no significant effect
on proteins. l-Pro2 action was at least partially reversible as measured by skin
electrical impedance. Toxicity in keratinocyte (HaCaT) and fibroblast (3T3) cell
lines showed IC(50) values ranging from tens to hundreds of MUM, which is
comparable with standard enhancers. Furthermore, l-Pro2 was rapidly decomposed in
plasma. In vivo transdermal absorption studies in rats confirmed the enhancing
activity of l-Pro2 and suggested its negligible skin toxicity and minimal effect
on transepidermal water loss. These properties make l-Pro2 a promising candidate
for potential clinical use.
PMID- 23154193
TI - Controlled delivery of heparin-binding EGF-like growth factor yields fast and
comprehensive wound healing.
AB - Wound healing is a dynamic process that relies on coordinated signaling molecules
to succeed. Heparin-binding epidermal growth factor (EGF)-like growth factor (HB
EGF) is proven to accelerate healing, however precise control over its
application is necessary to reduce side effects and achieve desired therapeutic
benefit. To achieve effective growth factor delivery we designed a bioactive
heparin-based coacervate. In vitro, HB-EGF released from the coacervate delivery
system displayed enhanced bioactivity and promoted human keratinocyte migration
while preserving cell proliferative capability. In a mouse excisional full
thickness wound model, controlled release of HB-EGF within the wound
significantly accelerated wound closure more effectively than an equal dosage of
free HB-EGF. Healing was induced by rapid re-epithelialization, granulation
tissue formation, and accompanied by angiogenesis. Consistent with in vitro
results, wounds treated with HB-EGF coacervate exhibited enhanced migration of
keratinocytes with retained proliferative potential, forming a confluent layer
for regained barrier function within 7 days. Collectively, these results suggest
that coacervate-based controlled release of HB-EGF may serve as a new therapy to
accelerate healing of cutaneous wounds.
PMID- 23154195
TI - Sox2 regulation of hair cell development: incoherence makes sense.
AB - The function of the inner ear relies on different specialized cell types: hair
cells, supporting cells and otic neurons. During development, these cell types
are generated from the neurosensory domain of the otic placode with a stereotyped
spatial and temporal pattern. We discuss here the role played by Sox2 in the
establishment of the neurosensory competence at early stages of inner ear
development, and how this resolves in the sequential generation of neurons and
hair cells. Sox2 is expressed in the neurosensory domain of the otic placode and
it is necessary and sufficient for hair cell development. The prosensory function
of Sox2 relies on its ability to directly bind Atoh1 regulatory regions and
activate its expression. This function is likely mediated through the interaction
with partner factors, some of which are just starting to be disclosed. However,
the regulation of proneural genes by Sox2 is seemingly contradictory, because it
also inhibits the function of Atoh1 and hence the differentiation of hair cells.
This is because Sox2 triggers an incoherent feed forward loop by which in
parallel to the activation of Atoh1, Sox2 also induces inhibitory factors that
counteract its function. As a result, neurosensory competence is established in
the early otic placode but hair cell differentiation procrastinated. More
generally, this suggests that cell diversification may arise from the selective
de-repression of an initial multicompetent state.
PMID- 23154196
TI - Effects of passive, moderate-level sound exposure on the mature auditory cortex:
spectral edges, spectrotemporal density, and real-world noise.
AB - Persistent, passive exposure of adult cats to bandlimited tone pip ensembles or
sharply-filtered white noise at moderate levels (~70 dB SPL) leads to a long-term
suppression of spontaneous and sound-evoked activity in the region(s) of primary
auditory cortex (AI) normally tuned to the exposure spectrum, and to an
enhancement of activity in one or more neighboring regions of AI, all in the
apparent absence of hearing loss. Here, we first examined the effects of passive
exposure to a more structured, real-world noise, consisting of a mix of power
tool and construction sounds. This "factory noise" had less pronounced effects on
adult cat AI than our previous random tone pip ensembles and white noise, and
these effects appeared limited to the region of AI tuned to frequencies near the
sharp factory noise cutoff at 16 kHz. To further investigate the role of sharp
spectral edges in passive exposure-induced cortical plasticity, a second group of
adult cats was exposed to a tone pip ensemble with a flat spectrum between 2 and
4 kHz and shallow cutoff slopes (12 dB/oct) on either side. Compared to our
previous ensemble with the same power in the 2-4 kHz band but very steep slopes,
exposure to the overall more intense, sloped stimulus had much weaker effects on
AI. Finally, we explored the issue of exposure stimulus spectrotemporal density
and found that low aggregate tone pip presentation rates of about one per second
sufficed to induce changes in the adult AI similar to those characteristic of our
previous, much denser exposures. These results are discussed in light of the
putative mechanisms underlying exposure-induced auditory cortical plasticity, and
the potential adverse consequences of working or living in moderately noisy
environments.
PMID- 23154197
TI - Risk modelling in quality clinical registries: monitoring lesion treatment
failure rate in percutaneous coronary interventions.
AB - AIMS: This paper describes the development of a risk adjustment (RA) model
predictive of individual lesion treatment failure in percutaneous coronary
interventions (PCI) for use in a quality monitoring and improvement program.
METHODS AND RESULTS: Prospectively collected data for 3972 consecutive
revascularisation procedures (5601 lesions) performed between January 2003 and
September 2011 were studied. Data on procedures to September 2009 (n=3100) were
used to identify factors predictive of lesion treatment failure. Factors
identified included lesion risk class (p<0.001), occlusion type (p<0.001),
patient age (p=0.001), vessel system (p<0.04), vessel diameter (p<0.001),
unstable angina (p=0.003) and presence of major cardiac risk factors (p=0.01). A
Bayesian RA model was built using these factors with predictive performance of
the model tested on the remaining procedures (area under the receiver operating
curve: 0.765, Hosmer-Lemeshow p value: 0.11). Cumulative sum, exponentially
weighted moving average and funnel plots were constructed using the RA model and
subjectively evaluated. CONCLUSION: A RA model was developed and applied to SPC
monitoring for lesion failure in a PCI database. If linked to appropriate quality
improvement governance response protocols, SPC using this RA tool might improve
quality control and risk management by identifying variation in performance based
on a comparison of observed and expected outcomes.
PMID- 23154198
TI - Early identification of asymptomatic subjects at increased risk of heart failure
and cardiovascular events: progress and future directions.
AB - Increasing evidence for a latent, preclinical phase of cardiac pathology prior to
the development of symptomatic heart failure has fuelled interest in the
potential of developing a screening program for early disease detection and
intervention. Cardiac biomarkers have shown promise in identifying subjects with
significant left ventricular dysfunction and more recently to assist in
cardiovascular risk stratification. However, a number of questions remain
regarding the use of these biomarkers for screening purposes. In particular,
appropriate cut-off levels and adjustment for individual patient characteristics
still need to be established and further cost-effectiveness studies are required
before screening programs can be undertaken. Given the enormous and increasing
burden of cardiac failure worldwide, the potential of these biomarkers to
identify those at greatest risk of the condition, either alone or as part of a
hybrid screening strategy is of great interest to the cardiology community. The
aim of this review is to outline evidence behind the argument for screening,
discuss the remaining barriers to its development and implementation and
highlight potential areas for future research.
PMID- 23154199
TI - Educating men about prostate cancer in the workplace.
AB - Prostate cancer is a common cancer affecting men worldwide. Few men access health
services with respect to early detection. Workplace health education initiatives
can promote behavior change in men. A total of 12 in-depth interviews with men
were conducted in this study to examine how a workplace-based educational
campaign on prostate cancer influences the knowledge, awareness, and beliefs of
male workers on screening for prostate cancer. Analyses of interview transcripts
identified that men had a poor overall knowledge about prostate cancer, its
screening, and treatment. Participants were receptive to the introduction of
workplace-based health education initiatives to promote men's health issues but
recommended an integrated health approach that incorporated information delivered
by medical professionals, cancer survivors, supplemented with existing patient
education materials. Further research is required to formally evaluate the impact
of workplace-based education strategies on men's health.
PMID- 23154200
TI - A dialogue on men's health.
PMID- 23154201
TI - The impact of ovarian stimulation on the expression of candidate reprogramming
genes in mouse preimplantation embryos.
AB - Ovarian stimulation with gonadotrophins is an integral part of assisted
reproductive technologies in human subfertility/infertility treatment. Recent
findings have associated ovarian stimulation with the increased incidence of
imprinting disorders in humans as well as defects in genome-wide methylation
reprogramming and, in particular, imprinting in mice. Here, we present the first
study that determined the impact of ovarian stimulation on the expression of
developmentally important reprogramming genes (Apex1, Lig1, Lig3, Mbd2, Mbd3,
Mbd4, and Polb) in single early mouse morula embryos (16-cell stage). Using
absolute quantification of mRNA by quantitative real-time PCR, we observed an
association of ovarian stimulation with a downregulation of mRNAs encoding the
base excision repair proteins APEX1 and POLB as well as the 5-methyl-CpG-binding
domain protein MBD3 in individual morula embryos. Whole mount immunofluorescence
staining of early and late morula embryos with an antibody against APEX1 revealed
individual embryos with lower protein expression levels after ovarian stimulation
and a correlation of mRNA expression with protein abundance. Our data argue for a
negative impact of ovarian stimulation during female gametogenesis and/or early
embryo development affecting the expression of candidate reprogramming factors.
PMID- 23154202
TI - The impact of tunneled pleural catheters on the quality of life of patients with
malignant pleural effusions.
AB - BACKGROUND: Tunneled pleural catheters (TPC) are used in the management of
malignant pleural effusions (MPE), but the impact of this palliative procedure on
patient quality of life (QoL) has not been well described. OBJECTIVES: To
ascertain the impact of TPCs on symptoms and QoL of patients with recurrent MPE.
METHODS: Patients with recurrent MPE completed the EORTC QLQ-C30 and LC13 QoL
questionnaires at baseline, 2 and 14 weeks; FACIT-TS-G(c) treatment satisfaction
surveys were completed at 14 weeks. RESULTS: A total of 82 patients were
recruited. Thirty-seven patients (37/82, 45%) died prior to their 14-week follow
up appointment. Significant improvements in dyspnea at 2 weeks were demonstrated
with both dyspnea scores (LC13 baseline score 64.1, 2-week score 43.7, mean
change -20.4, n = 56, p < 0.001; C30 baseline score 78.9, 2-week score 46.6, mean
change -32.4, n = 68, p < 0.001), as well as with the MRC score (baseline median
score 4, 2-week score 3, n = 70, p < 0.001). Global health status/QoL was also
significantly improved at 2 weeks (baseline score 34.1, 2-week score 46.3, mean
change 12.3, n = 68, p < 0.001). Improvements in cough, fatigue and all
functional scales were noted at 2 weeks. The improvements in dyspnea and global
health status/QoL were maintained to 14 weeks in surviving subjects and there was
further improvement in the MRC score at 14 weeks. Patients who completed the
FACIT-TS-G survey demonstrated overall satisfaction with TPC treatment.
CONCLUSIONS: TPCs are associated with a significant improvement in global health
status, QoL and dyspnea at the 2-week time point in patients with recurrent MPE.
PMID- 23154203
TI - Long-term changes in the personality and psychopathological profile of opiate
addicts after nucleus accumbens ablative surgery are associated with treatment
outcome.
AB - OBJECTIVE: To investigate the long-term outcome and changes of the personality
and psychopathological profile of opiate addicts after bilateral stereotactic
nucleus accumbens (NAc) ablative surgery. METHODS: 60 patients were followed up
for 5 years and abstinent status and adverse events were evaluated. NAc lesion
volumes and locations were obtained by postoperative MRI scans. The Chinese
version of the Eysenck Personality Questionnaire (EPQ-RSC), the Symptom Checklist
90-Revised (SCL-90-R), the Beck Depression Inventory (BDI), the Yale-Brown
Obsessive Compulsive Scale (Y-BOCS) and the World Health Organization's Quality
of Life Questionnaire - Brief Version (WHOQOL-BREF) were administered to the
patients before and 5 years after the stereotactic surgery. RESULTS: The total
abstinence rate of all patients in their 5th postoperative year was 47.4%. The
abstinent patients had a significantly larger lesion volume than the relapsed
ones, but a larger lesion volume also increased the risk of adverse events. 5
years after surgery, the abstinent patients showed significant decreases on the
Psychoticism (EPQ-P) and Neuroticism (EPQ-N) scores by EPQ-RSC, a significant
decline on the Global Severity Index and the subscores in all 10 dimensions by
SCL-90-R, significant decreases on the BDI and Y-BOCS scores, and significant
improvements on the scores of all domains by WHOQOL-BREF, while for the relapsed
patients, only the subscores of obsessive-compulsive by SCL-90-R and the Y-BOCS
scores significantly decreased. Postoperative analysis revealed that the
abstinent patients had a significantly better score than the relapsed ones by
various instruments, and NAc lesion volumes and locations did not correlate with
the outcome of any of these instruments. CONCLUSION: The bilateral ablation of
NAc by stereotactic neurosurgery was a feasible method for alleviating
psychological dependence on opiate drugs and preventing a relapse. Long-term
follow-up suggested that surgery can improve the personality and
psychopathological profile of opiate addicts with a trend towards normal levels,
provided persistent abstinence can be maintained; relapse, on the other hand, may
ruin this effect.
PMID- 23154204
TI - Postural adjustments in catching: on the interplay between segment stabilization
and equilibrium control.
AB - The purpose of this study was to investigate postural adjustments in one-handed
ball catching. Specifically, the functional role of anticipatory postural
adjustments (APA) during the initial arm raising and subsequent postural
adjustments (SPA) for equilibrium control and ball-hand impact were scrutinized.
Full-body kinematics and kinetics allowed an analysis of the mechanical
consequences of raising up the arm and preparing for ball-hand impact. APA for
catching were suggested to be for segment stabilization. SPA had a functional
role for equilibrium control by an inverted pendulum mechanism but were also
involved in preparing for the impact of the ball on the hand, which was
illustrated by an increased postural response at the end of the movement. These
results were compared with raising up the arm in a well-studied reaction-time
task, for which an additional counter rotation equilibrium mechanism was
observed. Together, our findings demonstrate that postural adjustments should be
investigated in relation to their specific functional task constraints, rather
than generalizing the functional role of these postural adjustments over
different tasks.
PMID- 23154205
TI - Adolescent varicocele-is the 20/38 harbinger a durable predictor of testicular
asymmetry?
AB - PURPOSE: Part of the management of adolescent varicocele is trying to
prognosticate who with testicular asymmetry will have catch-up growth with
observation and who will have persistent asymmetry. We previously reported that
catch-up growth is rare when peak retrograde flow greater than 38 cm per second
is associated with 20% or greater asymmetry (ie the 20/38 harbinger). We sought
to determine if this 20/38 cutoff held true with a larger series, and what peak
retrograde flow value should be used when 15% instead of 20% asymmetry is chosen
as the cutoff. MATERIALS AND METHODS: We analyzed patients from our large
varicocele registry who had undergone at least 2 duplex Doppler ultrasounds and
had been observed for at least 10 months in the interim. Outcomes were determined
regarding those who met the 20/38 cutoff and what peak retrograde flow value
could be used to recommend surgery when 15% to 19.9% asymmetry was included in
the cutoff value. RESULTS: Of 355 adolescent boys with left varicocele 44 (mean
age 14.0 years, range 9 to 20) were followed with observation initially and met
the 20/38 cutoff, while 9 additional patients met the 15/38 cutoff (initial
asymmetry 15% to 19.9%). When combining both groups, only 3 boys had catch-up
growth to less than 15% on followup. Thus, 50 of 53 patients did not demonstrate
catch-up growth after a mean followup of 15.5 months (range 10 to 44).
CONCLUSIONS: Not only does a peak retrograde flow of greater than 38 cm per
second hold up for predicting persistent/worsening asymmetry when combined with a
20% asymmetry cutoff, it also is an excellent predictor of persistent and/or
worsening asymmetry when combined with a 15% asymmetry cutoff. Therefore, it
might be unnecessary to follow an adolescent boy with observation who is at or
above this 15/38 cutoff.
PMID- 23154206
TI - B7-h1 as a biomarker for therapy failure in patients with favorable histology
Wilms tumor.
AB - PURPOSE: A minority of children with Wilms tumor will experience tumor
recurrence. In a previous pilot study we found an association between expression
of an immune costimulatory molecule, B7-H1, and tumor recurrence in favorable
histology Wilms tumor. We sought to verify the prognostic value of B7-H1 as a
biomarker in favorable histology Wilms tumor. MATERIALS AND METHODS: We performed
a nested case-control study of tumors from the Fifth National Wilms Tumor Study.
We randomly selected 44 children unsuccessfully treated (cases) and 49 who were
successfully treated for favorable histology Wilms tumor (controls). Cases and
controls were matched based on tumor stage, and the analysis was restricted to
children who underwent initial resection. We excluded patients with stage IV or V
disease and those treated with chemotherapy or radiation. Tumor specimens were
stained for B7-H1 expression. RESULTS: Of the 93 total samples analyzed 60 (65%)
demonstrated B7-H1 staining, with staining diffusely present in 13 (22%) and
blastema predominant in 34 (57%). B7-H1 expression was associated with failure of
initial therapy (p = 0.006). Patients with tumors showing less than 20% B7-H1
positive cells were at lower risk for treatment failure, while those with tumors
exhibiting greater than 60% B7-H1 positive cells were at greater risk for
treatment failure. This association appeared to be independent of tumor stage.
CONCLUSIONS: B7-H1 expression by favorable histology Wilms tumor is associated
with an increased risk of failure of initial therapy.
PMID- 23154207
TI - Primary severe hypospadias: comparison of reoperation rates and parental
perception of urinary symptoms and cosmetic outcomes among 4 repairs.
AB - PURPOSE: We compared complication rates, urinary symptoms and cosmetic outcomes
as perceived by parents of patients undergoing 1 of 4 repairs for proximal
hypospadias associated with ventral curvature. MATERIALS AND METHODS: A total of
93 patients underwent hypospadias repair between 2004 and 2010. In patients
requiring no urethral plate transection the repair consisted of tubularized
incised plate urethroplasty (26 patients) or onlay island flap urethroplasty
(31). In patients requiring urethral plate transection the repair consisted of
onlay island flap on albuginea (18 patients) or 2-stage repair (18).
Complications were assessed by chart review. A customized questionnaire and the
Pediatric Penile Perception Score were administered to parents to evaluate their
perception of urinary symptoms and cosmetic outcomes, respectively. RESULTS:
After a median followup of 4.5 years (range 2.2 to 8.4) complications developed
in 21 patients (23%) without any difference among procedures or between patients
who did and did not require urethral plate transection. Parents of 75 patients
(80%) participated in the survey without differences among repairs (p = 0.35).
Reported urinary symptoms were not different among repairs. For Pediatric Penile
Perception Score the only difference concerned the question about penile length
(p = 0.03), with the score being significantly better for the techniques
requiring urethral plate transection (p = 0.05). The 2-stage repair had a
significantly better score for the question about penile length and overall
Pediatric Penile Perception Score than all other techniques. CONCLUSIONS: Overall
complication rates were comparable among repairs and did not increase after
urethral plate transection. Urinary symptoms as reported by parents were
comparable among the procedures. Perceived penile length was significantly better
after urethral plate transection. The 2-stage repair yielded the best cosmetic
results.
PMID- 23154208
TI - The specificity of urinary aquaporin 1 and perilipin 2 to screen for renal cell
carcinoma.
AB - PURPOSE: Renal cancer is frequently asymptomatic until late stages of the disease
and it has a poor prognosis when not discovered early. AQP1 and PLIN2 are
recently discovered, sensitive urine biomarkers of clear cell and papillary
kidney cancer. We validated these biomarkers in a second cohort of patients and
determined the effect of common kidney diseases on specificity. MATERIALS AND
METHODS: Urine samples were obtained from 36 patients with clear cell or
papillary kidney cancer, 43 controls, 44 patients with documented urinary tract
infection, 24 diagnosed with diabetic nephropathy and 18 diagnosed with
glomerulonephritis. Urine levels of AQP1 and PLIN2 normalized to urine creatinine
were determined by a sensitive, specific Western blot procedure. RESULTS:
Compared with controls, urine AQP1 and PLIN2 levels in patients with kidney
cancer were 23-fold and fourfold greater, respectively, and they decreased 83% to
84% after tumor excision. There was a linear correlation between urine AQP1 and
PLIN2 levels, and tumor size (each p <0.001). Urine AQP1 and PLIN2 levels in
patients with kidney cancer were 11 to 23-fold and 17 to 25-fold greater,
respectively, than in patients with the common kidney diseases. CONCLUSIONS: The
ability of urine AQP1 and PLIN2 to identify patients with kidney cancer compared
to controls was validated in a second cohort of patients. Common kidney diseases
do not adversely increase urine AQP1 and PLIN2 levels or decrease their
specificity to screen for renal cancer.
PMID- 23154210
TI - A(2a) adenosine receptor mediates PKA-dependent glutamate release from synaptic
like vesicles and Ca(2+) efflux from an IP(3)- and ryanodine-insensitive
intracellular calcium store in astrocytes.
AB - BACKGROUND/AIMS: The mechanism underlying transmitter release from astrocytes is
not fully understood. The present study examined A(2a) adenosine receptor
mediated glutamate release and intracellular Ca(2+) rise in cultured rat
hippocampal astrocytes. METHODS: Intracellular amino acids were measured with
HPLC. Glutamate release from astrocytes and intracellular Ca(2+) mobilizations
were monitored in the NADH imaging, FM1-43 imaging, and fura-2 imaging. The siRNA
to silence the A(2a) adenosine receptor-targeted gene was constructed and
transfected into cells. RESULTS: Glutamate was condensed in 'synaptic-like
vesicle' fractions. In the NADH imaging, CGS21680, an agonist of A2a adenosine
receptors, increased NADH fluorescent signals, that reflects glutamate release,
and the effect was inhibited by DMPX, an inhibitor of A(2a) adenosine receptors,
H-89, a PKA inhibitor, vesicular transport inhibitors, or botulinum toxin-A, an
exocytosis inhibitor. In the FM1-43 imaging to see vesicular recycling, CGS21680
decreased FM1-43 fluorescent signals, that was also prevented by DMPX, H-89,
vesicular transport inhibitors, or botulinum toxin-A. CGS21680 increased
intracellular Ca(2+) concentrations both in Ca(2+)-containing and -free
extracellular solution. The Ca(2+) rise was inhibited by DMPX, H-89, or the
vesicular transport inhibitor brefeldin A, but it was not affected by inhibitors
for phospholipase C, IP(3) receptor, and ryanodine receptor. CGS21680-induced
glutamate release and intracellular Ca(2+) rise were prevented by knocking-down
A(2a) adenosine receptor. CONCLUSION: The results of the present study show that
A(2a) adenosine receptor/PKA promotes glutamate release from synaptic-like
vesicles and stimulates Ca(2+) efflux from an IP(3)- and ryanodine-insensitive
intracellular calcium store.
PMID- 23154211
TI - Best allograft survival from share-35 kidney donors occurs in middle-aged adults
and young children-an analysis of OPTN data.
AB - BACKGROUND: On October 2005, the Organ Procurement and Transplant Network
implemented a new allocation policy for kidney transplants (KTX) from deceased
donors (DD) ages <35 years to increase an access to transplantation from young
donors for pediatric (ages <18 years) recipients, which is known as Share-35
(S35). However, many of these kidneys were allocated to adult recipients. The
intent of this study was to analyze the graft outcomes from S35 kidneys in
pediatric and adult recipients, stratified further by recipient age, to assess if
recipient age affects the outcome from these presumably ideal kidneys. METHODS:
The Organ Procurement and Transplant Network database from October 2005 to
November 2010 involving 18,461 S35-KTX was used to calculate cumulative graft
survival (CGS), death-censored graft survival, and patient survival using Kaplan
Meier estimates. The differences between survival curves were tested for
significance by log-rank method after adjusting for various donor, recipient, and
transplant-associated variables. RESULTS: With S35 implementation, children
received a higher proportion of DD ages <35 years. Within the pediatric age
group, adolescents (ages 13-17 years) had the worst CGS. Among adults, the
highest CGS was obtained in middle-aged adults, whereas young adults (ages 18-25
years) showed worse CGS. CGS in young children (ages <12 years) was comparable
with those in middle-aged adults. In older adults (ages >55 years), CGS was
lowered by higher patient death rates. CONCLUSIONS: Recipient age affects
allograft survival from high-quality young DD kidneys, such as S35 kidneys. Best
survival occurs in middle-aged adults and in children ages <12 years, whereas
adolescents and young adults do not derive an optimal benefit.
PMID- 23154212
TI - Influence of delayed graft function and acute rejection on outcomes after kidney
transplantation from donors after cardiac death.
AB - BACKGROUND: Delayed graft function (DGF) and acute rejection (AR) exert an
adverse impact on graft outcomes after kidney transplantation using organs from
donation after brain-stem death (DBD) donors. Here, we examine the impact of DGF
and AR on graft survival in kidney transplants using organs from donation after
cardiac death (DCD) donors. METHODS: We conducted a single-center retrospective
study of DCD and DBD donor kidney transplants. We compared 1- and 4-year graft
and patient survival rates, as well as death-censored graft survival (DCGS)
rates, between the two groups using univariate analysis, and the impact of DGF
and AR on graft function was compared using multivariate analysis. RESULTS:
Eighty DCD and 206 DBD donor transplants were analyzed. Median follow-up was 4.5
years. The incidence of DGF was higher among DCD recipients (73% vs. 27%,
P<0.001), and AR was higher among DBD recipients (23% vs. 9%, P<0.001). One-year
and 4-year graft survival rates were similar (DCD 94% and 79% vs. DBD 90% and
82%). Among recipients with DGF, the 4-year DCGS rate was better for DCD
recipients compared with DBD recipients (100% vs. 92%, P=0.04). Neither DGF nor
AR affected the 1-year graft survival rate in DCD recipients, whereas in DBD
recipients, the 1-year graft survival rate was worse in the presence of DGF (88%
vs. 96%, P=0.04) and the 4-year DCGS rate was worse in the presence of AR (88%
vs. 96%, P=0.04). CONCLUSION: Despite the high incidence of DGF, medium-term
outcomes of DCD kidney transplants are comparable to those from DBD transplants.
Short-term graft survival from DCD transplants is not adversely influenced by DGF
and AR, unlike in DBD transplants.
PMID- 23154214
TI - The early treatment of bradykinin angioedema, a challenge for emergency medicine.
PMID- 23154213
TI - Altering the dewetting characteristics of ultrathin gold and silver films using a
sacrificial antimony layer.
AB - Solid state dewetting of ultrathin films is the most straightforward means of
fabricating substrate-supported noble metal nanostructures. This assembly process
is, however, quite inflexible, yielding either densely packed smaller structures
or widely spaced larger structures. Here, we demonstrate the utility of
introducing a sacrificial antimony layer between the substrate and noble metal
overlayer. We observe an agglomeration process which is radically altered by the
concurrent sublimation of antimony. In stark contrast with conventional
dewetting, where the thickness of the deposited metal film determines the
characteristic length scales of the assembly process, it is the thickness of the
sacrificial antimony layer which dictates both the nanoparticle size and
interparticle spacing. The result is a far more flexible self-assembly process
where the nanoparticle size and areal density can be varied widely.
Demonstrations show nanoparticle areal densities which are varied over four
orders of magnitude assembled from the identical gold layer thickness, where the
accompanying changes to nanostructure size see a systematic shift in the
wavelength of the localized surface plasmon resonance. As a pliable self-assembly
process, it offers the opportunity to tailor the properties of an ensemble of
nanostructures to meet the needs of specific applications.
PMID- 23154215
TI - Recent advances in fluorescent nucleic acid probes for living cell studies.
AB - Living cell studies can offer tremendous opportunities for biological and disease
studies. Due to their high sensitivity and selectivity, minimum interference with
living biological systems, ease of design and synthesis, fluorescent nucleic acid
probes (FNAPs) have been widely used in living cell studies, such as for
intracellular detection, cell detection, and cell-to-cell communication. Here, we
review the general requirements and the recent developments in FNAPs for living
cell studies. We broadly classify these designs as hybridization probes and
aptamer probes. For hybridization probes, we describe recently developed designs,
such as nanomaterial-based and amplification-based hybridization probes. For
aptamer probes, we discuss four general paradigms that have appeared most
frequently in the literature: nanomaterial-based, nanomachine-based, cell surface
anchored and activatable aptamer probe designs in vivo. FNAPs promise to open up
new and exciting opportunities in biological marks detection for a wide range of
biological and medical applications.
PMID- 23154217
TI - Food menus evaluation for most liked products in children from Puna, region of
Argentina.
AB - The aim of this study was to investigate the acceptability of varied food menus,
preferred by children of 11-14 years located at Puna (3500 m.a.s.l.), in young
urban people. The children drew "the preferred menu" which showed that the
consumption of vegetables as a main course was comfortable when it was consumed
in the form of soups and mixed vegetables. However, some imbalances were detected
when evaluating the percentage of daily nutritional values and the caloric
distribution of nutrients. Consumer's hedonic scores showed significant
acceptability to the cheese empanadas, Andean potato cake and Andean mashed
potato. The free word association test suggested that, because of their
relationship with culture, the Andean mashed potato, verde potato stew with
charqui and anchi of apple could be offered as a traditional food. The
acceptability of meals was largely related to the meals having the highest input
of energy, fat and carbohydrates but containing the least content of protein and
dietary fiber.
PMID- 23154216
TI - Modification of the school cafeteria environment can impact childhood nutrition.
Results from the Wise Mind and LA Health studies.
AB - Recent changes in nutrition standards for the National School Lunch and School
Breakfast Programs assume that modification of the nutritional serving practices
of school cafeterias will result in improved childhood nutrition in the school
environment. The primary aim of this paper is to summarize the findings from two
recent cluster randomized controlled trials (Wise Mind and LA Health) that tested
the hypothesis that modification of school cafeteria environments, including
changes in nutrition standards, would yield beneficial changes in childhood
nutrition and healthy eating in the school lunch environment. A secondary aim was
to investigate the association of participant characteristics and changes in
nutrition and healthy eating. A third aim was to investigate the relationships
between the food intake of children and: (1) foods selected by the children and
(2) food that was uneaten during the lunch meal (plate waste). The studies used
similar approaches for modifying the school cafeteria environment and both
studies used the digital photography method to measure changes in food intake,
food selection, and plate waste. Both studies reported significant improvements
in childhood nutrition, and the LA Health study reported improved healthy eating,
following introduction of the cafeteria modification program in comparison to
baseline and/or control arms. These studies confirm the hypothesis that
interventions that modify the school cafeteria environment can beneficially
impact childhood nutrition.
PMID- 23154218
TI - Associations between home- and family-related factors and fruit juice and soft
drink intake among 10- to 12-year old children. The ENERGY project.
AB - The aim of this study is to investigate associations of family-related factors
with children's fruit drink/juice and soft drink consumption. A cross-sectional
survey among 10- to 12-year-old children and their parents in eight European
countries was conducted to gather this data. Key variables of interest were
children's self-reported fruit drink/juice and soft drink intake per day
(outcome) and family-related factors (based on parents' report) related to these
two behaviors (modeling, automaticity, availability, monitoring, permissiveness,
negotiating, communicating health beliefs, avoid negative modeling, self
efficacy, rewarding, and family consumption). 7915 Children (52% girls; mean
age=11.7 +/- 0.8 years) and 6512 parents (83% women; mean age=41.4 +/- 5.3 years)
completed the questionnaire. Multilevel regression analyses were used to examine
the aforementioned associations. Three of the 11 family-related factors
(modeling, availability, and family consumption) were positively associated with
children's fruit drink/juice and soft drink intake. Additionally, three family
related factors (permissiveness, monitoring, and self-efficacy) were solely
associated with soft drink intake and one family-related factor (communicating
health beliefs) was related to fruit drink/juice intake. Future interventions
targeting children's fruit drink/juice and soft drink intake should focus on the
home environment, parents and their practices, especially on parents' fruit
drink/juice and soft drink intake and availability of these beverages at home.
PMID- 23154219
TI - Watching a food-related television show and caloric intake. A laboratory study.
AB - Television watching has been positively associated with overeating and obesity.
How popular food-related television shows affects eating behavior has not been
examined. An experimental study was conducted to examine how exposure to a food
related television program affects amount and type of food consumed in adults
(N=80). Participants were randomized to watch a cooking or nature television
program and were then presented with 800 total calories of chocolate covered
candies, cheese curls, and carrots. Food was weighed before and after the ad
libitum eating session to determine amount consumed. After controlling for
dietary restraint, hunger and food preference, significantly more chocolate
covered candies were consumed among individuals who watched the cooking program
compared to the nature program. No significant differences between conditions
were found for overall caloric intake or for cheese curl or carrot consumption.
Findings suggest that watching food-related television programs may affect eating
behavior and has implications for obesity prevention and intervention efforts.
PMID- 23154220
TI - Comment on "Comparing proteins by their internal dynamics: exploring structure
function relationships beyond static structural alignments" by C. Micheletti.
PMID- 23154221
TI - The dynamic view of proteins: comment on "Comparing proteins to their internal
dynamics: exploring structure-function relationships beyond static structural
alignments".
PMID- 23154223
TI - B cells: IL-21 promotes B10 cell population expansion.
PMID- 23154222
TI - Recognition of CD1d-restricted antigens by natural killer T cells.
AB - Natural killer T (NKT) cells are innate-like T cells that rapidly produce a
variety of cytokines following T cell receptor (TCR) activation and can shape the
immune response in many different settings. There are two main NKT cell subsets:
type I NKT cells are typically characterized by the expression of a semi
invariant TCR, whereas the TCRs expressed by type II NKT cells are more diverse.
This Review focuses on the defining features and emerging generalities regarding
how NKT cells specifically recognize self, microbial and synthetic lipid-based
antigens that are presented by CD1d. Such information is vitally important to
better understand, and fully harness, the therapeutic potential of NKT cells.
PMID- 23154225
TI - B cell responses: Born to be (a bit) wild.
PMID- 23154226
TI - Standardization in flow cytometry: correct sample handling as a priority.
PMID- 23154227
TI - Proposed accelerated FDA approvals for special medical use.
PMID- 23154224
TI - Eosinophils: changing perspectives in health and disease.
AB - Eosinophils have been traditionally perceived as terminally differentiated
cytotoxic effector cells. Recent studies have profoundly altered this simplistic
view of eosinophils and their function. New insights into the molecular pathways
that control the development, trafficking and degranulation of eosinophils have
improved our understanding of the immunomodulatory functions of these cells and
their roles in promoting homeostasis. Likewise, recent developments have
generated a more sophisticated view of how eosinophils contribute to the
pathogenesis of different diseases, including asthma and primary
hypereosinophilic syndromes, and have also provided us with a more complete
appreciation of the activities of these cells during parasitic infection.
PMID- 23154228
TI - What have we learned about the treatment of type 2 diabetes? The evolving
paradigms.
AB - Insulin, the first treatment for diabetes, was discovered >90 years ago. Since
then, many new types of insulin have become available, including analogs that
more closely mimic the characteristics of endogenous insulin. In addition, oral
antidiabetes drugs and other types of injectable therapies have been approved for
the treatment of patients with type 2 diabetes. As newer treatments are approved
for type 2 diabetes, the choice and-paradoxically-the complexity of treatment
increases. The potential benefits of all treatment options must be carefully
balanced against potential adverse events to truly analyze the overall efficacy,
safety, tolerability, and potential long-term effects. The manner in which
outcomes are assessed and the methods employed to make such assessments have
changed over time. This review will address these issues as they are related to
therapies for type 2 diabetes, including insulin, oral antidiabetes drugs, and
incretin-based agents.
PMID- 23154229
TI - Direct thrombin inhibitors: a case indicating benefit from 'plasmapheresis' in
toxicity: a call for establishing "guidelines" in overdose and to find an
"antidote"!
AB - Patient presented with passage of fresh blood mixed with clots per rectum. In the
ER, she was found to have bright red blood per rectum with clots, with frank
blood on nasogastric tube. She was on dabigatran for atrial fibrillation and
aspirin, with intermittent intake of ibuprofen. Vitals were positive for
orthostatic hypotension. The pertinent findings in the physical examination were
altered mental status with orientation*1, weak peripheral pulses, irregularly
irregular heart rate, and bilateral pitting edema 2+ in bilateral lower
extremities. Patient was intubated and put on mechanical ventilation. A massive
transfusion protocol was followed. Laboratories and imaging:
hemoglobin/hematocrit, 7.2/22.1; white blood cells, 7.7, platelet, 210;
international normalized ratio, 2.5; prothrombin time, 19.2; activated partial
thromboplastin time, 88.2; CMP was WNL; BNP, 621; fibrinogen, 500 mg/dL.
Electrocardiogram showed atrial fibrillation with inferolateral ischemia.
Ultrasonography of the liver and gallbladder showed no acute pathology.
Echocardiogram showed an EF of 70% with hyperdynamic LV. Patient was transferred
to the intensive care unit. Dabigatran, aspirin, and nonsteroidal anti
inflammatory drugs were discontinued, and antihypertensives were held. She was
given blood and FFPs. Hemoglobin, hematocrit, and coagulation profile was
monitored every 6 hours. Gastroenterology, general surgery, interventional
radiology, and hematology services were called stat. IR placed a double-lumen,
power central venous catheter. In gastroenterology, EGD and colonoscopy was
performed, which showed active bleed at distal esophagus, stopped with local
epinephrine. No active bleed seen on colonoscopy. The patient was put on Nexium
drip. Hematology service recommended thrombin time (>200) and factors 2, 5, 7, 9,
10-41(l), 80, 68, 48(l), 61. Prothrombin time and activated partial
thromboplastin time mixing studies were done, which indicated the presence of
thrombin inhibition. Prothrombin complex concentrate at 50 U/kg was started to
reverse the effect of dabigatran, and platelets were transfused to reverse the
effect of aspirin. They also discussed that the half-life of dabigatran being 17
hours, and the drug would not be toxic at this point, as the patient was already
24-hour inpatient by now. The hemoglobin trend: 7.4->6.4->8.2->7.5->6.6. At this
point, the need for further intervention in form of hemodialysis or
plasmapheresis was considered. The patient was given plasmapheresis and
hemoglobin and hematocrit stabilized. The patient was kept on continued
mechanical ventilator support for the night and extubated next day. The
hemodynamics stabilized and the patient was transferred to the general medical
floors after 1 day of observation, after extubation.
PMID- 23154230
TI - The lifeblood of a practice.
PMID- 23154231
TI - Miniscrew implant-supported rapid maxillary expansion.
PMID- 23154232
TI - Class II treatment with the smart distalization technique.
PMID- 23154233
TI - Eruption of a labially impacted canine using a closed-flap technique and
orthodontic wire traction.
PMID- 23154234
TI - Miniscrew-retained pontics in growing patients: a biological approach.
PMID- 23154235
TI - Begg brackets as auxiliaries for thermoformed appliances.
PMID- 23154236
TI - Genetic variation in the scavenger receptor MARCO and its association with
chronic obstructive pulmonary disease and lung infection in 10,604 individuals.
AB - BACKGROUND: MARCO (macrophage receptor with collagenous structure) is a dominant
receptor for unopsonized particles and bacteria in the lungs. Reduced function of
this receptor due to genetic variation may be associated with susceptibility to
chronic obstructive pulmonary disease (COPD) and lung infection. OBJECTIVES: To
identify novel genetic variants in MARCO that are associated with reduced lung
function, or increased risk of COPD or lung infection. METHODS: We first screened
760 individuals with extreme lung phenotypes in a large general population study
to identify novel variants in the MARCO gene. We next genotyped the entire cohort
consisting of 10,604 individuals to assess the clinical relevance of these
variants. RESULTS: We identified 4 novel (R124H, K201N, P303L and G340W) and 5
previously described (H101Q, F282S, G319V, K387Q and E511D) non-synonymous
variants. When screening the entire cohort for these variants, we found low minor
allele frequencies ranging from 0.005 to 5%. None of the individual MARCO
genotypes were associated with reduced lung function, or risk of COPD or lung
infection. H101Q heterozygotes had an increased odds ratio for sepsis of 2.2 (95%
CI: 1.1-4.4) compared to non-carriers, but none of the other MARCO genotypes were
associated with the risk of sepsis. CONCLUSIONS: We identified 9 non-synonymous
variants in the MARCO gene and showed that these variants are not major risk
factors for COPD or lung infection in the Danish population. H101Q heterozygotes
had increased sepsis risk, but further research is required to confirm this
finding. This study is the first to examine genetic variants in MARCO and the
risk of COPD and infections in humans.
PMID- 23154237
TI - Neuroimmunomodulatory alterations in non-lesional peritoneum close to peritoneal
endometriosis.
AB - OBJECTIVES: An imbalance in the ratio of sensory to sympathetic nerve fibre (NF)
density in peritoneal endometriotic lesions (pEL) has recently been demonstrated
and leads to the assumption that this preponderance of the sensory pro
inflammatory milieu is a major cause of pain in endometriosis. Therefore, the
density of sensory and sympathetic NFs was determined in distal unaffected
peritoneum of endometriosis patients to be able to detect possible alterations in
unaffected peritoneum. METHODS: In serial pEL sections (n = 40), lesional and
matching unaffected peritoneum as well as healthy peritoneum (HP) from patients
without endometriosis (n = 15) were immunohistochemically analysed to identify
protein gene product 9.5-, substance P- and tyrosine hydroxylase-positive NFs
(intact, sensory and sympathetic NFs, respectively). In addition, the amount of
immune cell infiltrates and the expression of nerve growth factor (NGF) and
interleukin (IL)-1beta in nerves of peritoneal endometriotic specimens were
compared to those in the HP. RESULTS: The overall NF density in the non-lesional,
unaffected peritoneum of endometriosis patients is significantly reduced in
comparison to both HP and pEL, while sensory NFs remain the same; the sympathetic
NF density is significantly decreased compared to HP, but is still higher than
the density close to the pEL. Immune cell infiltrates as well as NGF and IL-1beta
expression in nerves is significantly elevated in distal unaffected peritoneum in
comparison to HP. CONCLUSION: The altered NF density in the non-lesional,
unaffected peritoneum of endometriosis patients suggests new aspects in the
understanding of the development of endometriosis and pain management in
endometriosis.
PMID- 23154238
TI - A widespread and distinctive form of amphipod intersexuality not induced by known
feminising parasites.
AB - Intersexuality occurs in a diverse range of animals, and its study offers
insights into basic reproductive biology. Investigations in amphipods suggest
intersexuality results from incomplete feminisation caused by sex-distorting
parasites. It has also been noted that 2 intersex phenotypes occur in males of
the amphipod Echinogammarus marinus, an external phenotype, in which males
possess rudimentary brood plates, and an internal phenotype, in which only an
ovotestis is present. This study examines the relationship between these
phenotypes and finds their prevalences are independent. In addition, a cross
species microarray reveals the testicular transcriptomes of the intersex
phenotypes are distinct from that of normal males and, most crucially, each
other. Furthermore, the internal intersex phenotype, unlike the external
phenotype, shows no correlation with infection by known feminising parasites.
These findings suggest the male intersex phenotypes should not be considered
stages on a single spectrum of intersexuality. Rather, they support the
hypothesis that internal and external intersexuality are divergent phenotypes
with separate causal mechanisms and point to the existence of a distinct and
geographically widespread form of amphipod intersexuality caused by an unknown
factor.
PMID- 23154239
TI - Stimulation of non-neuronal muscarinic receptors enhances chemerin/ChemR23 system
in dysfunctional endothelial cells.
AB - AIMS: Endothelial cells play a pivotal role in vascular intimal inflammation
during cardiovascular diseases. The chemerin/ChemR23 system in endothelial cells
is one of physiological mechanisms that regulate inflammatory responses. Our
previous studies indicated that stimulation of non-neuronal muscarinic receptor
(NNMR) improved endothelial dysfunction. However, the relationship between the
chemerin/ChemR23 signaling axis and NNMR in endothelial cell is poorly
understood. Here, we first investigated whether the modulation of
chemerin/ChemR23 signaling axis is involved in NNMR-mediated endothelial
protection. MAIN METHODS: Cultured rat aortic endothelial cells (RAECs) were
used. The ChemR23 protein expression and chemerin secretion were measured using
Western blot analysis. The gene expression level of ChemR23 was examined with
reverse transcriptase PCR (RT-PCR). The production of nitric oxide (NO) was
determined by a nitrate reductase assay kit. KEY FINDINGS: A sharp decline of
chemerin secretion and ChemR23 protein/gene expression was observed in RAECs
after exposed to homocysteine at concentration of 0.5 mmol/L. Arecoline (10
MUmol/L) pretreatment increased ChemR23 protein expression as well as mRNA
expression, and enhanced the secretion of chemerin. Arecoline could also reverse
the decreased ChemR23 mRNA expression induced by uric acid, high glucose, or
oxidized low-density lipoprotein. Furthermore, the modulation of arecoline on
chemerin/ChemR23 signaling axis was absolutely abolished in the presence of the
nonselective muscarinic receptors antagonist atropine 1 MUmol/L. Additionally,
arecoline improved endothelial dysfunction by increasing the reduced NO
production induced by uric acid, which was blocked by anti-ChemR23 antibody.
SIGNIFICANCE: The chemerin/ChemR23 signaling axis participates in NNMR-mediated
protection against endothelial dysfunction in cardiovascular system.
PMID- 23154240
TI - Analytical surveillance of emerging drugs of abuse and drug formulations.
AB - Uncontrolled recreational drugs are proliferating in number and variety. Effects
of long-term use are unknown, and regulation is problematic, as efforts to
control one chemical often lead to several other structural analogs. Advanced
analytical instrumentation and methods are continuing to be developed to identify
drugs, chemical constituents of products, and drug substances and metabolites in
biological fluids. Several mass spectrometry based approaches appear promising,
particularly those that involve high resolution chromatographic and mass
spectrometric methods that allow unbiased data acquisition and sophisticated data
interrogation. Several of these techniques are shown to facilitate both targeted
and broad spectrum analyses, the latter of which are often of particular benefit
when dealing with misleadingly labeled products or assessing a biological matrix
for illicit drugs and metabolites. The development and application of novel
analytical approaches such as these will help to assess the nature and degree of
exposure and risk and, where necessary, inform forensics and facilitate
implementation of specific regulation and control measures.
PMID- 23154241
TI - Endoplasmic reticulum stress in HepG2 cells inhibits apolipoprotein A-I
secretion.
AB - AIMS: Endoplasmic reticulum (ER) stress modulates gene expression and has been
implicated in causing dyslipidemias. To determine if ER stress may contribute to
hypoalphalipoproteinemia through suppression of apo A-I gene expression, human
hepatoma cell line Hep G2 was treated with ER stress inducers and the changes in
apo A-I gene expression were compared to albumin gene expression. MAIN METHODS:
HepG2 cells were treated with tunicamycin (TM) and thapsigargin (TG), two potent
inducers of ER stress, and apo A-I and albumin protein levels, mRNA levels, and
promoter activity were measured. ER stress was measured using the ER stress
responsive alkaline phosphatase assay and by Western blot quantitation of ER
stress markers such as glucose-regulated protein-78 (GRP-78), phosphorylated Jun
N-terminal kinase (phospho-JNK), total JNK, phosphorylated eukaryotic initiation
factor 2 alpha (phospho eIF2alpha), and total eIF2alpha. KEY FINDINGS: TM and TG
induced ER stress in HepG2 cells and reduced apo A-I and albumin secretion in a
dose-dependent manner. Intracellular albumin levels increased in cells treated
with TM and TG while intracellular apo A-I levels decreased. Albumin mRNA and
albumin gene promoter activity were reduced in proportion to the decrease in
albumin secreted while changes in the apo A-I mRNA levels and promoter activity
were modest and did not account for the reduction in apo A-I secretion.
SIGNIFICANCE: These results indicate that apo A-I secretion is inhibited by ER
stress possibly by affecting cellular degradation pathways. However, ER stress
does not affect apo A-I secretion by regulating gene expression.
PMID- 23154242
TI - Expression of the histamine H4 receptor in dermal and articular tissues.
AB - Histamine H(4) receptor was identified in 2000 and is the most recently
identified of the four histamine receptors. It is expressed primarily in immune
cells and is involved in physiologic functions related to inflammation and
allergy. Recently, the H(4) receptor was highlighted as a promising therapeutic
target in atopic dermatitis, asthma, and chronic arthritis. In fact, some H(4)
receptor antagonists have reached clinical trials for the treatment of asthma,
atopic dermatitis, and allergic rhinitis. Based on an initial assessment of
distribution, the H(4) receptor has been referred to as the histamine receptor of
the hematopoietic system. However, the H(4) receptor has also been implicated in
the regulation of other non-hematopoietic systems. Here, we review the expression
and function of the H(4) receptor with a focus on dermal and articular tissues.
In skin, the H(4) receptor is expressed in both the epidermis and dermis, with
stronger receptor expression in the epidermis. In articular tissue, H(4) receptor
expression has been detected in synovial cells. Chondrocytes, a major cell
sources for cartilage tissue engineering, also express the H(4) receptor. Further
understanding of the functions of H(4) receptors in non-hematopoietic cells might
lead to novel treatments for diseases with unmet needs.
PMID- 23154243
TI - Retraction: Development of paclitaxel loaded NIPAAm/VP polymeric nanoparticles
for efficacy enhancement against human cancer therapy.
AB - This article has been withdrawn at the request of the author(s) and/or editor.
The Publisher apologizes for any inconvenience this may cause. The full Elsevier
Policy on Article Withdrawal can be found at
http://www.elsevier.com/locate/withdrawalpolicy.
PMID- 23154244
TI - Agmatine promotes the migration of murine brain endothelial cells via multiple
signaling pathways.
AB - AIMS: The combination of adhesion and migration of endothelial cells (ECs) is an
integral process for evolution, organization, repair and vessel formation in
living organisms. Agmatine, a polycationic amine existing in brain, has been
investigated to exert neuroprotective effects. Up to date, there are no studies
reporting that agmatine modulates murine brain endothelial (bEnd.3) cells
migration. In the present study, we intend to investigate the role of agmatine in
bEnd.3 cells migration and the molecular mechanism mediating this action. MAIN
METHODS: The effect of agmatine on the bEnd.3 cells migration was examined by
migration assay, and the mechanism involved for this effect was investigated by
western blot analysis and NO contents measurements. KEY FINDINGS: Agmatine
treatment (50, 100 and 200 MUM) significantly accelerated bEnd.3 cells migration
in a concentration-dependent manner. Western blotting revealed that agmatine
treatment significantly induced vascular endothelial growth factor (VEGF), VEGF
receptor 2 (Flk-1/KDR or VEGFR2), phosphatidylinositol 3-kinase (PI3K),
Akt/protein kinase B (also known as PKB, PI3K downstream effector protein),
endothelial nitric oxide synthase (eNOS) nitric oxide (NO; product by eNOS) and
intercellular adhesion molecule 1 (ICAM-1) expressions during bEnd.3 cells
migration. The expression of ICAM-1 and migration of bEnd.3 cells, induced by
agmatine, were significantly attenuated by treatment of wortmannin, a specific
PI3K inhibitor. SIGNIFICANCE: Taken together, we provide the first evidence that
activation of VEGF/VEGFR2 and the consequential PI3K/Akt/eNOS/NO/ICAM-1 signaling
pathways are serial events, through which the treatment of agmatine could lead to
bEnd.3 cells migration.
PMID- 23154245
TI - Hydroxychloroquine-induced cardiomyopathy that presented as pulmonary
hypertension: a newly noted complication.
AB - We examined a 63-year-old woman with progressive dyspnea. Two years prior to
admission to our hospital, she had been diagnosed with rheumatoid arthritis and
treated with hydroxychloroquine (HCQ) with a cumulative dose of 164 g. In
addition, 2 months earlier, she had been diagnosed with connective tissue disease
related pulmonary artery hypertension. We performed an electrocardiogram and
noted complete atrioventricular block. A transthoracic echocardiogram showed
pulmonary hypertension. Due to the unclear nature of the pulmonary hypertension,
we performed cardiac catheterization and right ventricular endomyocardial biopsy.
Cardiac catheterization revealed that pulmonary hypertension was due to left
ventricular dysfunction. Electron microscopy of the cardiac biopsy demonstrated a
curvilinear body, diagnostic of HCQ toxicity. Thus, we diagnosed pulmonary
hypertension owing to left heart disease and complete atrioventricular block that
resulted from HCQ toxicity. Insertion of a permanent pacemaker and
discontinuation of HCQ dramatically improved the disease state. This is the first
report of this type of cardiac complication with HCQ; it raises the awareness
that HCQ may cause cardiac complications despite a small cumulative dose relative
to doses reported in other cases. Furthermore, we emphasize that cardiac
catheterization played a critical role in the differential diagnosis from
pulmonary hypertension associated with connective tissue disease.
PMID- 23154247
TI - Dermatofibrosarcoma protuberans in childhood.
AB - Dermatofibrosarcoma protuberans (DFSP) is a fibrohistiocytic tumor of
intermediate malignancy that is very rare in childhood. Only 6% of these tumors
present in children. Clinical diagnosis is very difficult in the early stages of
disease, but to ensure appropriate treatment it is important to identify DFSP as
early as possible and rule out benign conditions that are more common at this
age. The clinical presentation and histopathologic and molecular characteristics
of DFSP are similar in children and adults. Clinical diagnosis is, however, more
difficult in children and requires a high degree of suspicion. The absence of
characteristic features and the rarity of this tumor explain why diagnosis is
often delayed. Complete surgical excision of the tumor is very important to
reduce the risk of recurrence. This article presents a review of current
knowledge about the management of DFSP in children and examines the latest
treatment options.
PMID- 23154246
TI - "Right time, right place" health communication on Twitter: value and accuracy of
location information.
AB - BACKGROUND: Twitter provides various types of location data, including exact
Global Positioning System (GPS) coordinates, which could be used for
infoveillance and infodemiology (ie, the study and monitoring of online health
information), health communication, and interventions. Despite its potential,
Twitter location information is not well understood or well documented, limiting
its public health utility. OBJECTIVE: The objective of this study was to document
and describe the various types of location information available in Twitter. The
different types of location data that can be ascertained from Twitter users are
described. This information is key to informing future research on the
availability, usability, and limitations of such location data. METHODS: Location
data was gathered directly from Twitter using its application programming
interface (API). The maximum tweets allowed by Twitter were gathered (1% of the
total tweets) over 2 separate weeks in October and November 2011. The final
dataset consisted of 23.8 million tweets from 9.5 million unique users.
Frequencies for each of the location options were calculated to determine the
prevalence of the various location data options by region of the world, time
zone, and state within the United States. Data from the US Census Bureau were
also compiled to determine population proportions in each state, and Pearson
correlation coefficients were used to compare each state's population with the
number of Twitter users who enable the GPS location option. RESULTS: The GPS
location data could be ascertained for 2.02% of tweets and 2.70% of unique users.
Using a simple text-matching approach, 17.13% of user profiles in the 4
continental US time zones were able to be used to determine the user's city and
state. Agreement between GPS data and data from the text-matching approach was
high (87.69%). Furthermore, there was a significant correlation between the
number of Twitter users per state and the 2010 US Census state populations (r >=
0.97, P < .001). CONCLUSIONS: Health researchers exploring ways to use Twitter
data for disease surveillance should be aware that the majority of tweets are not
currently associated with an identifiable geographic location. Location can be
identified for approximately 4 times the number of tweets using a straightforward
text-matching process compared to using the GPS location information available in
Twitter. Given the strong correlation between both data gathering methods, future
research may consider using more qualitative approaches with higher yields, such
as text mining, to acquire information about Twitter users' geographical
location.
PMID- 23154248
TI - Carbon dioxide laser treatment of epidermal nevi: response and long-term follow
up.
AB - BACKGROUND AND OBJECTIVES: Epidermal nevi, which are benign skin growths, have
been treated using a range of approaches, with varying results. Topical
treatments are ineffective and, while surgical excision is a more definitive
treatment, it causes scar formation. In recent decades, epidermal nevi have been
treated with various types of laser therapy. We describe our experience with the
use of carbon dioxide (CO(2)) laser therapy to treat epidermal nevi and
inflammatory linear verrucous epidermal nevi (ILVEN). PATIENTS AND METHODS:
Twenty patients (15 with epidermal nevi and 5 with ILVEN) underwent CO(2) laser
treatment at our hospital between 2002 and 2010. RESULTS: Response was good (>50%
reduction in lesion size) in 50% of cases and excellent (>75% reduction) in 30%.
A greater resistance to treatment was observed in patients with ILVEN (only 40%
had a good response). Long-term follow-up (at least 18 months) showed a
recurrence rate of 30%. The side effects were hypopigmentation (25% of patients)
and scarring (20%). CONCLUSIONS: We consider CO(2) laser therapy to be the
treatment of choice for epidermal nevi as it is well tolerated and has proven to
be safe and effective in the long term. While the response in patients with ILVEN
was limited, CO(2) laser therapy might be a good option for selected cases or for
palliative treatment since no other treatments have yet proven effective in this
setting.
PMID- 23154249
TI - Hyperkeratosis and scaling in identical twins.
PMID- 23154250
TI - Dermatosis neglecta or terra firma-forme dermatosis.
PMID- 23154251
TI - Managing adverse effects and complications in completing treatment for hepatitis
C virus infection.
AB - The addition of direct-acting antivirals (DAAs) to hepatitis C virus (HCV)
treatment regimens has made treatment more effective and patient management more
complex. Shepherding patients through a full course of HCV therapy requires
motivation and involvement on the part of the patient and the physician. Indeed,
physician inexperience and lack of confidence in guiding patients through the
challenges of treatment appears to be a primary reason for early discontinuation
of therapy. Among the many complications of HCV treatment that must be managed
efficiently and effectively are depression and other psychiatric disorders;
hematologic abnormalities including DAA- and ribavirin-associated anemia and
peginterferon alfa-associated neutropenia and thrombocytopenia; rash and drug
eruptions, including telaprevir-associated rash; and weight loss. Practical
considerations in management of these common complications are offered. This
article summarizes a presentation by Kenneth E. Sherman, MD, PhD, at the IAS-USA
live continuing medical education course held in New York in June 2012.
PMID- 23154252
TI - Cardiovascular risk and dyslipidemia management in HIV-infected patients.
AB - HIV infection and antiretroviral therapy each appear to increase cardiovascular
disease risk. Increased risk may be attributable to the inflammatory effects of
HIV infection and dyslipidemia associated with some antiretroviral agents. The
prevalence of cardiovascular disease is increasing as patients live longer, age,
and acquire traditional coronary heart disease (CHD) risk factors. In general,
any additional cardiovascular risk posed by HIV infection or antiretroviral
therapy is of potential concern for patients who are already at moderate or high
risk for CHD. Long-term and well-designed studies are needed to more accurately
ascertain to what degree HIV infection and antiretroviral therapy affect long
term cardiovascular disease risk. Management of dyslipidemia to reduce CHD risk
in HIV-infected patients is much the same as in the general population, with the
cornerstone consisting of statin therapy and lifestyle interventions. Smoking
cessation is a major step in reducing CHD risk in those who smoke. This article
summarizes a presentation by James H. Stein, MD, at the IAS-USA live continuing
medical education activity held in New York City in March 2012.
PMID- 23154253
TI - Syphilis negatively influences the response to hepatitis C virus treatment in an
HIV-infected patient.
PMID- 23154254
TI - Beyond telaprevir and boceprevir: resistance and new agents for hepatitis C virus
infection.
AB - The addition of the hepatitis C virus (HCV) protease inhibitors telaprevir and
boceprevir to peginterferon alfa with ribavirin therapy has increased cure rates
in HCV infection. Numerous other direct-acting antivirals (DAAs) are in advanced
stages of development, including next-generation protease inhibitors,
nonstructural protein (NS) 5A inhibitors, and nonnucleoside and nucleos(t)ide
NS5B polymerase inhibitors. The classes have different potencies, different
resistance mutation profiles, and different barriers to the emergence of
resistance. A comprehensive table of resistance mutations for classes of DAAs is
presented. Numerous combinations of DAAs with or without ribavirin have been
evaluated in early studies of interferon alfa-free regimens, with results
indicating that cure is indeed possible with such therapy and suggesting that
identification of regimens that could produce cure in the majority of patients
may occur within the foreseeable future. This article summarizes a presentation
by David L. Wyles, MD, at the IAS-USA live continuing medical education activity
held in New York in June 2012.
PMID- 23154257
TI - Virology: giant viruses--movers and shakers.
PMID- 23154258
TI - Immunology: splice-tailored to fit the bug.
PMID- 23154260
TI - Structural vaccinology starts to deliver.
AB - Following the impact of the genomics revolution on vaccine research and the
development of reverse vaccinology, it was predicted that another new approach,
structure-based antigen design, would become a driving force for vaccine
innovation. Now, 5 years on, there are several examples of how structure-based
design, or structural vaccinology, can deliver new vaccine antigens that were not
possible before. Here, we discuss some of these examples and the contribution of
structural vaccinology to our understanding of the protective epitopes of
important bacterial and viral pathogens.
PMID- 23154263
TI - Add-on-therapy with bevacizumab in children and adolescents with poor prognosis
non-CNS solid tumors.
AB - Bevacizumab is increasingly being used in adult patients with cancer and children
with central nervous system (CNS) tumors. Little, however, is known about the
efficacy, risks, and benefits of bevacizumab administration in non-CNS tumors of
childhood. The aim of the present study was to report on bevacizumab administered
as add-on-therapy for poor prognosis non-CNS solid tumors of childhood and
adolescence, including a prospective evaluation of side effects of bevacizumab.
Seven patients (female: n = 5; median age, 14.5 years) with relapsed (n = 4) or
primary metastatic (n = 3) solid non-CNS tumors received bevacizumab at 5-10
mg/kg body weight intravenously every 2-3 weeks. Assessment of cardiac function,
thyroid hormone levels, urine analysis, and radiographic responses were carried
out every 3 months. The median time of bevacizumab treatment was 10 (range, 5-17)
months. Patients received a median of 16 (range, 10-38) bevacizumab infusions.
With a median follow-up of 25 (range, 13-38) months, five patients relapsed after
7-25 months and three of them died. Two patients are still in complete remission
for 31 and 32 months, respectively. Fraction shortening decreased in two
patients. Bevacizumab was associated with new-onset increase in basal thyroid
stimulating hormone (n = 3), mild proteinuria/hematuria (n = 5), intermittent
hypertension (n = 2), hypertension requiring antihypertensive medication (n = 3),
and epistaxis (n = 2). In two patients, therapy with bevacizumab was terminated
because of side effects. Selected patients with relapsed or primary metastatic
solid non-CNS tumors of childhood and adolescence might benefit from add-on
therapy with bevacizumab. Although the side effects were usually mild, cardiac
monitoring seems to be essential during and after the administration of
bevacizumab.
PMID- 23154264
TI - Impact of 3D conformal radiotherapy on lung function of patients with lung
cancer: a prospective study.
AB - BACKGROUND: The development of three-dimensional conformal radiotherapy (3D-RT)
has enabled the restriction of the dose to normal lung, limiting radiation
induced lung injury. OBJECTIVES: This study was designed to describe the time
course of lung function until 7.5 months after 3D-RT in patients with lung
cancer, and assess the relationship between lung function changes and dose-volume
histogram (DVH) analysis or computed tomography scan changes. Radiation doses
were optimized according to recent guidelines. METHODS: Sixty-five lung cancer
patients treated with 3D-RT agreed to participate in this prospective, hospital
based study. Lung volumes, forced expiratory volume in 1 s (FEV1) and diffusing
capacity of the lung for carbon monoxide (DLCO) were measured before radiotherapy
(RT), 10 weeks, 4 and 7.5 months after the beginning of 3D-RT. RESULTS: Eleven
lung cancer patients (17%) developed grade 2-3 respiratory symptoms after RT. At
7.5 months, vital capacity (VC) was 96 +/- 2%, total lung capacity (TLC) 95 +/-
2%, FEV1 93 +/- 2% and DLCO 90 +/- 2% of the initial value. Only 15% of patients
showed pulmonary function reduction > 20%. Patients with FEV1 or DLCO < 60%
before RT did not show significant changes after RT. There were weak correlations
between reduction of VC, TLC, FEV1 or DLCO and radiation dosimetric parameters
and between reduction of VC or FEV1 and radiation-induced pneumonitis images.
CONCLUSIONS: In lung cancer, the reduction of lung function within 7.5 months
after 3D-RT was small and correlated, albeit weakly, with DVH parameters.
Patients with initially impaired lung function showed tiny changes in spirometry
and DLCO values.
PMID- 23154265
TI - The role of intraoperative fluid optimization using the esophageal Doppler in
advanced gynecological cancer: early postoperative recovery and fitness for
discharge.
AB - OBJECTIVE: To determine the effect of fluid optimization using esophageal Doppler
monitoring (EDM) when compared to standard fluid management in women who undergo
major gynecological cancer surgery and whether its use is associated with reduced
postoperative morbidity. METHODS: From January 2009 to December 2010, women
undergoing laparotomy for pelvic masses or uterine cancer had either fluid
optimization using intraoperative EDM or standard fluid replacement without using
EDM. Cases were selected from 2 surgeons to control for variability in surgical
practice. Demographic and surgical details were collected prospectively.
Univariate and multivariate analyses were performed to quantify the association
between the use of EDM with "early postoperative recovery" and "early fitness for
discharge." RESULTS: A total of 198 women were operated by the 2 prespecified
surgeons; 79 women had fluid optimization with EDM, whereas 119 women had
standard anesthetic care. The use of ODM was associated with earlier
postoperative recovery (adjusted odds ratio, 2.83; 95% confidence interval, 1.20
6.68; P = 0.02) and earlier fitness for discharge (adjusted odds ratio, 2.81; 95%
confidence interval, 1.01-7.78; P = 0.05). Women with advanced-stage disease in
the "EDM" group resumed oral diet earlier than women in the "no EDM" group
(median, 1 day vs 2 days; P = 0.02). These benefits with EDM did not extend to
women with early-stage disease/benign/borderline tumors. No significant
difference in postoperative complications was noted. CONCLUSIONS: Intraoperative
fluid optimization with EDM in women with advanced gynecological cancer may be
associated with improved postoperative recovery and early fitness for discharge.
Studies with adequate power are needed to investigate its role in reducing
postoperative complications.
PMID- 23154261
TI - Microbial life in the phyllosphere.
AB - Our knowledge of the microbiology of the phyllosphere, or the aerial parts of
plants, has historically lagged behind our knowledge of the microbiology of the
rhizosphere, or the below-ground habitat of plants, particularly with respect to
fundamental questions such as which microorganisms are present and what they do
there. In recent years, however, this has begun to change. Cultivation
independent studies have revealed that a few bacterial phyla predominate in the
phyllosphere of different plants and that plant factors are involved in shaping
these phyllosphere communities, which feature specific adaptations and exhibit
multipartite relationships both with host plants and among community members.
Insights into the underlying structural principles of indigenous microbial
phyllosphere populations will help us to develop a deeper understanding of the
phyllosphere microbiota and will have applications in the promotion of plant
growth and plant protection.
PMID- 23154262
TI - Animal models for HIV/AIDS research.
AB - The AIDS pandemic continues to present us with unique scientific and public
health challenges. Although the development of effective antiretroviral therapy
has been a major triumph, the emergence of drug resistance requires active
management of treatment regimens and the continued development of new
antiretroviral drugs. Moreover, despite nearly 30 years of intensive
investigation, we still lack the basic scientific knowledge necessary to produce
a safe and effective vaccine against HIV-1. Animal models offer obvious
advantages in the study of HIV/AIDS, allowing for a more invasive investigation
of the disease and for preclinical testing of drugs and vaccines. Advances in
humanized mouse models, non-human primate immunogenetics and recombinant
challenge viruses have greatly increased the number and sophistication of
available mouse and simian models. Understanding the advantages and limitations
of each of these models is essential for the design of animal studies to guide
the development of vaccines and antiretroviral therapies for the prevention and
treatment of HIV-1 infection.
PMID- 23154266
TI - Reduced expression of DKK3 is associated with adverse clinical outcomes of
uterine cervical squamous cell carcinoma.
AB - OBJECTIVE: The aim of this study was to assess the expression of DKK3 protein and
its target, beta-catenin, in uterine cervical squamous cell carcinoma and to
determine potential clinical correlations. MATERIALS AND METHODS: Six carcinoma
in-situ (CIS) tissues and 88 invasive cervical cancer tissues were included in
the study. Twenty-two normal cervical tissues and one gastric cancer tissue were
used as controls. The expression of DKK3 and beta-catenin proteins was evaluated
by immunohistochemical analysis. Clinical and pathological parameters were
obtained from medical records. Survival data were estimated using Kaplan-Meier
estimates and compared with a log-rank test. Multivariate analysis was performed
using the Cox regression method. RESULTS: DKK3 was predominantly present in the
cytoplasm. Beta-catenin was observed only on the cellular membrane of both normal
and cancer cells in contrast to earlier reports, in which beta-catenin was
localized to the cytoplasm and nucleus of cancer cells. The expressions of beta
catenin and DKK3 were not correlated. Three of 6 CIS (50%) and 57 of 88 invasive
cancer specimens (64.8%) had lower DKK3 expression than normal controls. DKK3
expression was decreased in a stage-dependent manner (P = 0.021). The patients
with low expression of DKK3 were older than those with high expression of DKK3 (P
< 0.01). Moreover, the patients with low DKK3 expression had a significantly
lower 5-year disease-free survival rate than those with high DKK3 expression (P =
0.026). A multivariate analysis showed that International Federation of
Gynecology and Obstetrics clinical stage and parametrial involvement were
independent prognostic factors. CONCLUSION: Decreased DKK3 expression was
associated with advanced International Federation of Gynecology and Obstetrics
clinical stages and was predictive of lower disease-free survival in patients
with cervical squamous cell carcinoma. DKK3 may be implicated in cervical
carcinogenesis through a beta-catenin-independent mechanism.
PMID- 23154267
TI - Starving tumors: inhibition of glycolysis reduces viability of human endometrial
and ovarian cancer cells and enhances antitumor efficacy of GnRH receptor
targeted therapies.
AB - OBJECTIVE: Increased glycolysis for energy production is necessary for survival
of tumor cells and thus represents a selective therapeutic target. We have
analyzed in vitro whether inhibition of glycolysis can reduce the viability of
human endometrial and ovarian cancer cells and whether it can enhance the
antitumor efficacy of GnRH receptor-targeted therapies. MATERIALS AND METHODS:
Cell viability of ovarian and endometrial cancer cells treated without or with
glycolysis inhibitor 2-Deoxy-D-Glucose (2DG) alone or in combination with GnRH-II
antagonist [Ac-D2Nal(1), D-4Cpa(2), D-3Pal(3,6)(8),Leu, D-Ala(10)]GnRH-II or with
cytotoxic GnRH-I agonist AEZS-108 (AN-152) was measured using alamar blue assay.
Induction of apoptosis was analyzed using TUNEL assay and quantified by
measurement of loss of mitochondrial membrane potential. Apoptotic signaling was
measured by quantification of activated caspase-3 by using the Western blot
technique. RESULTS: Treatment of endometrial and ovarian cancer cells with
glycolysis inhibitor 2DG resulted in a significant decrease of cell viability and
a significant increase of apoptosis. Treatment with 2DG in combination with the
GnRH-II antagonist or with AEZS-108 resulted in a significant reduced viability
compared with single-agent treatments. The observed reduction in viability was
due to induction of apoptosis. Also for apoptosis induction, a significant
stronger effect in the case of cotreatments compared with single-agent treatments
could be observed. These additive effects could be correlated to increased
activation of caspase-3. CONCLUSIONS: The glycolytic phenotype of human
endometrial and ovarian cancer cells can be targeted for therapeutic
intervention. In addition, cotreatment of a glycolysis inhibitor with GnRH
receptor-targeted therapies might be a suitable therapy for GnRH receptor
positive human endometrial and ovarian cancers.
PMID- 23154268
TI - Prognostic significance of cell cycle- and invasion-related molecular markers and
genomic instability in primary carcinoma of the vagina.
AB - OBJECTIVE: This study aimed to analyze the prognostic value of DNA content and
biological markers for cell cycle regulation and invasion in primary carcinoma of
the vagina (PCV). MATERIAL AND METHODS: Seventy-two consecutive patients with
PCV, categorized as short-term (<= 2 years) and long-term (>= 8 years) survivors,
were evaluated for DNA content by image cytometry, and for expression of p53,
p21, cyclin A, Ki67, E-cadherin, and laminin-5gamma2 chain by
immunohistochemistry. The relationship between these biological markers and
histopathological and clinical parameters was assessed. RESULTS: All PCV showed
aneuploid DNA content. Most of the PCV patients showed no overexpression of p53
and high expression of p21, cyclin A, and Ki67. Loss or underexpression of E
cadherin was found in 94% (68/72) of PCV patients, and all patients showed
immunopositivity for the laminin-5gamma2 chain. Tumors with a vaginal
longitudinal location in the lower third or in the entire vagina more often had
overexpression of p53, high expression of Ki67 (P = 0.044), and underexpression
of E-cadherin (P = 0.038), than tumors confined only to the upper third.
Overexpression of p53 was significantly associated with short-term survival in
the univariate analysis, but not in the multivariate analysis adjusted for age at
diagnosis and tumor size. CONCLUSIONS: The expression level of some markers was
related to tumor location, which might be indicative of different genesis.
Overexpression of p53 was associated with short-term survival, but the only
independent predictors of survival were age at diagnosis and tumor size.
PMID- 23154269
TI - Molten-droplet synthesis of composite CdSe hollow nanoparticles.
AB - Many colloidal synthesis routes are not scalable to high production rates,
especially for nanoparticles of complex shape or composition, due to precursor
expense and hazards, low yields, and the large number of processing steps. The
present work describes a strategy to synthesize hollow nanoparticles (HNPs) out
of metal chalcogenides, based on the slow heating of a low-melting-point metal
salt, an elemental chalcogen, and an alkylammonium surfactant in octadecene
solvent. The synthesis and characterization of CdSe HNPs with an outer diameter
of 15.6 +/- 3.5 nm and a shell thickness of 5.4 +/- 0.9 nm are specifically
detailed here. The HNP synthesis is proposed to proceed with the formation of
alkylammonium-stabilized nano-sized droplets of molten cadmium salt, which then
come into contact with dissolved selenium species to form a CdSe shell at the
droplet surface. In a reaction-diffusion mechanism similar to the nanoscale
Kirkendall effect it is speculated that the cadmium migrates outwardly through
this shell to react with more selenium, causing the CdSe shell to thicken. The
proposed CdSe HNP structure comprises a polycrystalline CdSe shell coated with a
thin layer of amorphous selenium. Photovoltaic device characterization indicates
that HNPs have improved electron transport characteristics compared to standard
CdSe quantum dots, possibly due to this selenium layer. The HNPs are colloidally
stable in organic solvents even though carboxylate, phosphine, and amine ligands
are absent; stability is attributed to octadecene-selenide species bound to the
particle surface. This scalable synthesis method presents opportunities to
generate hollow nanoparticles with increased structural and compositional
variety.
PMID- 23154270
TI - The M235T polymorphism in the angiotensinogen gene and heart failure: a meta
analysis.
AB - BACKGROUND: The aim of the present study was to assess the association between
M235T polymorphism and heart failure using a meta-analysis. METHODS: A literature
search of Google Scholar, PubMed, the Cochrane Library and the China National
Knowledge Infrastructure database (January 1990-April 2012) was performed for
relevant studies. Statistical analyses were carried out using the Stata 12.0 to
combine all the relevant studies. Summary odds ratios (ORs) and 95% confidence
intervals (95% CIs) were calculated in a fixed-effects model and a random-effects
model when appropriate. The pooled ORs were performed under the allelic contrast
(T vs M), the dominant (TT + MT vs. MM) and the recessive models (TT vs MT + MM).
Begg's test was used to measure publication bias. RESULTS: A total of six case
control studies including 842 patients and 1054 controls were enrolled in this
meta-analysis. Overall, there was a significant association between
angiotensinogen (AGT) gene M235T polymorphism and risk of heart failure in the
subgroup analysis under the allelic contrast (T vs M: OR = 1.48, 95% CI: 1.04
2.11) and the dominant model (TT+MT vs MM: OR=1.67, 95% CI: 1.13-2.46) in the
Caucasian population. CONCLUSIONS: The current meta-analysis suggests that M235T
polymorphism might be associated with increased risk of heart failure in
Caucasians.
PMID- 23154271
TI - Serum uric acid in patients with Parkinson's disease and vascular parkinsonism: a
cross-sectional study.
AB - BACKGROUND: Elevation of serum uric acid (UA) is correlated with a decreased risk
of Parkinson's disease (PD); however, the association and clinical relevance of
serum UA levels in patients with PD and vascular parkinsonism (VP) are unknown.
OBJECTIVE: We performed a cross-sectional study of 160 Chinese patients with PD
and VP to determine whether UA levels in patients could predict the outcomes.
METHODS: Serum UA levels were divided into quartiles and the association between
UA and the severity of PD or VP was investigated in each quartile. RESULTS: The
serum levels of UA in PD were significantly lower than those in normal subjects
and VP. The serum UA levels in PD patients were significantly correlated with
some clinical parameters. Strong correlations were observed in male PD patients,
but significant correlations were observed only between UA and the non-motor
symptoms (NMS) of burden of sleep/fatigue and mood in female PD patients. PD
patients in the lowest quartile of serum UA levels had significant correlations
between UA and the unified Parkinson's disease rating scale, the modified Hoehn
and Yahr staging scale and NMS burden for attention/memory. CONCLUSION: Our
findings support the hypothesis that subjects with low serum UA levels may be
more prone to developing PD and indicate that the inverse relationship between UA
and severity of PD was robust for men but weak for women. Our results strongly
imply that either low serum UA level is a deteriorative predictor or that serum
UA level serves as an indirect biomarker of prediction in PD but not in VP
patients.
PMID- 23154272
TI - Synthesis and modifications of phosphinic dipeptide analogues.
AB - Pseudopeptides containing the phosphinate moiety (-P(O)(OH)CH(2)-) have been
studied extensively, mainly as transition state analogue inhibitors of
metalloproteases. The key synthetic aspect of their chemistry is construction of
phosphinic dipeptide derivatives bearing appropriate side-chain substituents.
Typically, this synthesis involves a multistep preparation of two individual
building blocks, which are combined in the final step. As this methodology does
not allow simple variation of the side-chain structure, many efforts have been
dedicated to the development of alternative approaches. Recent achievements in
this field are summarized in this review. Improved methods for the formation of
the phosphinic peptide backbone, including stereoselective and multicomponent
reactions, are presented. Parallel modifications leading to the structurally
diversified substituents are also described. Finally, selected examples of the
biomedical applications of the title compounds are given.
PMID- 23154273
TI - Nucleoside triphosphates--building blocks for the modification of nucleic acids.
AB - Nucleoside triphosphates are moldable entities that can easily be functionalized
at various locations. The enzymatic polymerization of these modified triphosphate
analogues represents a versatile platform for the facile and mild generation of
(highly) functionalized nucleic acids. Numerous modified triphosphates have been
utilized in a broad palette of applications spanning from DNA-tagging and
labeling to the generation of catalytic nucleic acids. This review will focus on
the recent progress made in the synthesis of modified nucleoside triphosphates as
well as on the understanding of the mechanisms underlying their polymerase
acceptance. In addition, the usefulness of chemically altered dNTPs in SELEX and
related methods of in vitro selection will be highlighted, with a particular
emphasis on the generation of modified DNA enzymes (DNAzymes) and DNA-based
aptamers.
PMID- 23154274
TI - TLRs and IFNs: critical pieces of the autoimmunity puzzle.
AB - Discoveries revealing the molecular basis of innate immune responses,
particularly the identification of Toll-like receptors (TLRs) as the major
recognition sensors for microbial and even self-molecules, have provided new
insights into the pathogenesis of both systemic and organ-specific autoimmune
diseases. These insights will permit the development of novel treatment
modalities for these disorders.
PMID- 23154275
TI - Autoantibodies, autoimmune disease, and the birth of immune diagnostics.
AB - The appearance of autoantibody to DNA followed sequentially by the disappearance
of anti-DNA and appearance of DNA antigen in a patient with systemic lupus
erythematosus demonstrated that autoantibodies participate in immune complex
mediated pathogenesis. Continuing studies showed that autoantibodies are also
useful biomarkers in clinical diagnosis and important reagents for elucidating
the structure and function of intracellular proteins in cell biology. Recently,
autoantibodies to tumor-associated antigens have been identified in cancer, and
these findings have expanded the field of cancer immunodiagnostics.
PMID- 23154276
TI - Better tools for assessing osteoporosis.
AB - Some 30 years ago, we applied the newly described method of dual photon
absorptiometry (DPA) to demonstrate that osteoporotic women with vertebral
fractures had lost substantially more bone from the vertebrae than controls. This
opened a whole new field of research into the determinants of bone loss and
fractures in the axial skeleton and set the stage for subsequent development of
dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography
(QCT), which are now the standard methods for assessing osteoporosis severity and
treatment efficacy.
PMID- 23154277
TI - Tumors exposed to acute cyclic hypoxia show increased vessel density and delayed
blood supply.
AB - The purpose of this study was to investigate the effect of acute cyclic hypoxia
on tumor vasculature. A-07 human melanoma xenografts growing in dorsal window
chambers were used as tumor model. Acute cyclic hypoxia was induced by
periodically exposing tumor-bearing mice to a low oxygen atmosphere. The hypoxia
treatment consisted of 12 cycles of 10 min of low O(2) (8% O(2) in N(2)) followed
by 10 min of air for a total of 4 hr. The treatment started the first day after
tumor initiation, and was given daily for 9 days. Vascular morphology was
assessed from high-resolution transillumination images, and tumor blood supply
was assessed from first-pass imaging movies recorded after a bolus of 155 kDa
tetramethylrhodamine isothiocyanate-labeled dextran had been administered
intravenously. Hypoxia-treated tumors showed increased vessel density, decreased
interstitial distance, and delayed blood supply compared to control tumors. The
increase in vessel density was attributed to an increased number of small
vessels. In conclusion, acute cyclic hypoxia induced angiogenesis in A-07 tumors
resulting in increased density of small-diameter vessels and delayed tumor blood
supply.
PMID- 23154278
TI - Increasing acclimation period improves the reproducibility of short-heating local
thermal hyperemia.
AB - OBJECTIVES: The axon reflex (AR) can be induced by the activation of afferent C
fibers during local skin heating. The previously used long-heating local thermal
hyperemia (LTH) protocols tested AR flare by normalizing to endothelial-mediated
maximal vasodilatation to adjust capillary heterogeneity when the recording sites
were randomly selected. The AR flare induced by short local heating can be
reproducible without using the data from subsequent longer heating for
normalization when the recording sites were fixed with holders in the same
session. The aim of this study was to investigate the effect of acclimation
period on the intersession reproducibility of short-heating LTH when the
recording sites were relocated after a longer interval of 1-3 days. METHODS:
After 30 or 60 min acclimation, LTH with 5 min heating was assessed on bilateral
human forearms using single-point laser Doppler flowmetry. The test was repeated
at the same recording sites again at the same time 1-3 days later. Baseline and
heating blood flux were analyzed and the data were expressed as different forms.
Reproducibility of two tests was assessed using coefficient of variation (CV) and
intra-class correlation coefficient (ICC) statistics. RESULTS: The intersession
reproducibility of peak cutaneous vascular conductance (CVC) (CV=18.38%,
ICC=0.82), peak CVC change (CV=20.38%, ICC=0.83) and 4 min area-under-the-curve
(AUC) (CV=18.66%, ICC=0.75) of the right forearm and time to peak (CV=16.84%,
ICC=0.52) of the left forearm were acceptable after 30 min acclimation. When the
acclimation period was increased to 60 min, all of these data except 4 min AUC of
both sides reached an acceptable level. CONCLUSIONS: The AR flare induced by
short local heating is reproducible when the recording sites are relocated by a
predefined rule. The reproducibility of LTH on right forearm is different from
that on left forearm, and increasing acclimation period improves the
reproducibility.
PMID- 23154279
TI - Wall shear stress quantification in the human conjunctival pre-capillary
arterioles in vivo.
AB - Blood volume flow (Q), wall shear rate (WSR) and wall shear stress (WSS) were
quantified, for the first time, in the conjunctival pre-capillary arterioles of
normal human volunteers with diameters (D) between 6 and 12 MUm. The variation of
the blood velocity throughout the cardiac cycle was taken into account using high
speed video microcinematography. The dual effect of arteriolar diameter, firstly
on the WSR and secondly on the dynamic viscosity of blood, was taken into account
in the estimation of WSS. The average Q, WSR and WSS, throughout the cardiac
cycle ranged from 13 to 202 pl/s, 587 to 3515 s(-1) and 1.7 to 21.1 N/m(2)
respectively. The best fit power law equations, giving the increase of Q and the
decrease of WSR and WSS with diameter, are presented for the systolic and
diastolic phase as well as for the averages throughout the cardiac cycle.
According to the WSS best fit equation, the average WSS decreases from 10.5
N/m(2) at D=6 MUm down to 2.1 N/m(2) at D=12 MUm.
PMID- 23154280
TI - In vivo evaluation of venular glycocalyx during hemorrhagic shock in rats using
intravital microscopy.
AB - Hemorrhage is responsible for a large percentage of trauma-related deaths but the
mechanisms underlying tissue ischemia are complex and not well understood.
Despite the evidence linking glycocalyx degradation and hemorrhagic shock, there
is no direct data obtained in vivo showing glycocalyx thickness reduction in
skeletal muscle venules after hemorrhage. We hypothesize that damage to the
endothelial glycocalyx is a key element in hemorrhage pathophysiology and tested
the hypothesis that hemorrhage causes glycocalyx degradation in cremaster muscle
microvessels. We utilized intravital microscopy to estimate glycocalyx thickness
in 48 microvessels while other microvascular parameters were measured using non
invasive techniques. Systemic physiological parameters and blood chemistry were
simultaneously collected. We studied 27 post-capillary venules (<16 MUm diameter)
of 8 anesthetized rats subjected to hemorrhage (40% of total blood volume). Six
control rats were equally instrumented but not bled. Dextrans of different
molecular weights labeled with FITC or Texas Red were injected. Glycocalyx
thickness was estimated from the widths of the fluorescence columns and from
anatomical diameter. While control rats did not show remarkable responses, a
statistically significant decrease of about 59% in glycocalyx thickness was
measured in venules after hemorrhagic shock. Venular glycocalyx thickness and
local blood flow changes were correlated: venules with the greatest flow
reductions showed the largest decreases in glycocalyx. These changes may have a
significant impact in shock pathophysiology. Intravital microscopy and integrated
systems such as the one described here may be important tools to identify
mechanisms by which resuscitation fluids may improve tissue recovery and outcome
following hemorrhage.
PMID- 23154281
TI - Difference of foot posture in two cases of exercise-induced foot dystonia.
PMID- 23154282
TI - The p.G146A and p.P125P polymorphisms in the steroidogenic factor-1 (SF-1) gene
do not affect the risk for hypospadias in Caucasians.
AB - Hypospadias is a frequent congenital malformation in boys and is characterized by
incomplete fusion of the urethral folds. The steroidogenic factor-1 (SF-1, NR5A1)
gene plays a key role in hypothalamic-pituitary-steroidogenic organ development,
and has previously been reported to be mutated in individuals with 46,XY disorder
of sex development. Here, we investigated the role of SF-1 in hypospadias, a
milder form of 46,XY disorder of sex development. We performed direct sequencing
analysis of the SF-1 gene in 2 male Caucasian twins exhibiting very severe
hypospadias, and in 95 Caucasian boys with mild and severe hypospadias. We
further extended the analysis by investigating 332 mild and severe hypospadias
cases and 422 male controls using TaqMan assays. Our sequencing revealed a novel
heterozygous p.R313H (c.938G>A) missense mutation in each twin, and no mutations
in the 95 Caucasian cases. Instead, a missense p.G146A (c.437G>C), and a silent
known p.P125P (c.375C>T) polymorphism, respectively, was found in several of the
latter cases. Further investigation of the 2 polymorphisms in the larger material
of cases and controls showed no significant genotypic or allelic association. In
conclusion, the SF-1 gene may not play a significant role in the development of
hypospadias in Caucasians.
PMID- 23154283
TI - The role of dendritic cells in Mycobacterium tuberculosis infection.
AB - The immune response against Mycobacterium tuberculosis is multifactorial,
involving a network of innate and adaptive immune responses. Characterization of
the immune response, a clear understanding of the dynamics and interplay of
different arms of the immune response are critical to allow the development of
better tools for combating tuberculosis. Dendritic cells (DCs) are one of the key
cells in bridging innate and adaptive immune response through their significant
role in capturing, processing and presenting antigens. The outcome of interaction
of M. tuberculosis with DCs is not fully understood and the available reports are
contradictory were some findings reported that DCs strengthen the cellular immune
response against mycobacterium infection whereas others reported M. tuberculosis
impairs the function of DCs were infected DCs are poor stimulators of M.
tuberculosis Ag-specific CD4 T cells. Other studies showed that the outcome
depends on M. tuberculosis strain type and type of receptor on DCs during
recognition. In this review I shall highlight the recent findings in the outcome
of interaction of Mycobacterium tuberculosis with DCs.
PMID- 23154285
TI - The streptococcal hemoprotein receptor: a moonlighting protein or a virulence
factor?
AB - The beta-hemolytic group A streptococcus (GAS) is a major pathogen that readily
uses hemoglobin to satisfy its requirements for iron. The streptococcal
hemoprotein receptor in GAS plays a central role in heme utilization and binds
fibronectin and laminin in vitro. Shr inactivation attenuates the virulent M1T1
GAS strain in two murine infection models and reduces bacterial growth in blood
and binding to laminin. Shr impact on the globally disseminated M1T1 strain
underscores the importance of heme uptake in GAS pathogenesis and raises the
possibility of targeting heme-uptake proteins in the development of new methods
to combat GAS infections.
PMID- 23154284
TI - A dendrite in every pie: myeloid dendritic cells in HIV and SIV infection.
AB - Dendritic cells (DC) are a heterogeneous population of innate immune cells that
are fundamental to initiating responses against invading pathogens and regulating
immune responses. Myeloid DC (mDC) act as a bridge between the innate and
adaptive immune response during virus infections but their role in immunity to
human immunodeficiency virus (HIV) remains ill-defined. This review examines
aspects of the mDC response to HIV and its simian counterpart, simian
immunodeficiency virus (SIV), and emphasizes areas where our knowledge of mDC
biology and function is incomplete. Defining the potentially beneficial and
detrimental roles mDC play during pathogenic and stable infection of humans and
nonhuman primates is crucial to our overall understanding of AIDS pathogenesis.
PMID- 23154286
TI - Pathology in euthermic bats with white nose syndrome suggests a natural
manifestation of immune reconstitution inflammatory syndrome.
AB - White nose syndrome, caused by Geomyces destructans, has killed more than 5
million cave hibernating bats in eastern North America. During hibernation, the
lack of inflammatory cell recruitment at the site of fungal infection and erosion
is consistent with a temperature-induced inhibition of immune cell trafficking.
This immune suppression allows G. destructans to colonize and erode the skin of
wings, ears and muzzle of bat hosts unchecked. Yet, paradoxically, within weeks
of emergence from hibernation an intense neutrophilic inflammatory response to G.
destructans is generated, causing severe pathology that can contribute to death.
We hypothesize that the sudden reversal of immune suppression in bats upon the
return to euthermia leads to a form of immune reconstitution inflammatory
syndrome (IRIS). IRIS was first described in HIV-infected humans with low helper
T lymphocyte counts and bacterial or fungal opportunistic infections. IRIS is a
paradoxical and rapid worsening of symptoms in immune compromised humans upon
restoration of immunity in the face of an ongoing infectious process. In humans
with HIV, the restoration of adaptive immunity following suppression of HIV
replication with anti-retroviral therapy (ART) can trigger severe immune-mediated
tissue damage that can result in death. We propose that the sudden restoration of
immune responses in bats infected with G. destructans results in an IRIS-like
dysregulated immune response that causes the post-emergent pathology.
PMID- 23154287
TI - Deformed wing virus: the main suspect in unexplained honeybee deaths worldwide.
PMID- 23154288
TI - Molecular blueprint of uropathogenic Escherichia coli virulence provides clues
toward the development of anti-virulence therapeutics.
PMID- 23154289
TI - Turning up Francisella pathogenesis: the LPS thermostat.
PMID- 23154290
TI - The fate of not sensing phosphate: downregulation of type 1 fimbriae through
activation of the Pho regulon reduces E. coli urinary tract virulence.
PMID- 23154292
TI - Remarkable enhancement in ligand-exchange reactivity of thiolate-protected Au25
nanoclusters by single Pd atom doping.
AB - The effect of Pd doping on the ligand-exchange reactivity of
Au(25)(SC(12)H(25))(18) was studied by comparing the ligand-exchange reactivity
of [Au(25)(SC(12)H(25))(18)](-) and [PdAu(24)(SC(12)H(25))(18)](0) and the
results clearly demonstrate that, regardless of the kind of incoming thiols and
solvents, Pd doping greatly increases the rate of ligand exchange of
Au(25)(SC(12)H(25))(18), indicating an enhanced ease of ligand exchange.
PMID- 23154293
TI - Characterization of a new animal model of metabolic syndrome: the DahlS.Z
Lepr(fa)/Lepr(fa) rat.
AB - OBJECTIVE: The DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rat strain was established
from a cross between Dahl salt-sensitive rats and Zucker fatty (fa/fa) rats, the
latter of which harbor a missense mutation in the leptin receptor gene (Lepr). We
examined whether DS/obese rats might be a suitable animal model of metabolic
syndrome in humans. METHODS: The systemic pathophysiological and metabolic
characteristics of DS/obese rats were determined and compared with those of
homozygous lean littermates, namely, DahlS.Z-Lepr(+)/Lepr(+) (DS/lean) rats.
RESULTS: Systolic blood pressure was higher in DS/obese rats fed a normal diet
than in DS/lean rats at 11 weeks of age and thereafter. The survival rate of
DS/obese rats was significantly lower than that of DS/lean rats at 18 weeks. Body
weight, visceral and subcutaneous fat mass, as well as heart, kidney and liver
weights, were increased in DS/obese rats at 18 weeks compared with DS/lean rats.
Serum low-density lipoprotein (LDL)-cholesterol, triglyceride and insulin
concentrations, as well as the ratio of LDL-cholesterol to high-density
lipoprotein-cholesterol levels, were increased in DS/obese rats, whereas serum
glucose concentration did not differ significantly between DS/obese and DS/lean
rats. Creatinine clearance was decreased and urinary protein content was
increased in DS/obese rats, which also manifested lipid accumulation in the liver
and elevation of serum alanine aminotransferase levels. CONCLUSION: These results
show that the phenotype of DS/obese rats is similar to that of humans with
metabolic syndrome, and that these animals may thus be an appropriate model for
this condition.
PMID- 23154294
TI - Abdominal adiposity depots are correlates of adverse cardiometabolic risk factors
in Caucasian and African-American adults.
AB - OBJECTIVE: Accumulation of adipose tissue is associated with cardiometabolic
risks. Although visceral adipose tissue (VAT) has been strongly implicated in
this relationship, there is still some debate regarding the contribution of
abdominal subcutaneous adipose tissue (SAT). The purpose of this study was to
determine the contribution of abdominal SAT to cardiometabolic risk factors,
independent of total and visceral adiposity. These relationships were assessed in
Caucasian and African Americans. DESIGN: It is a cross-sectional analysis of the
Pennington Center Longitudinal Study. SUBJECTS: Data were extracted from 1246
participants. Total body fat mass (FM) was measured by dual-energy X-ray
absorptiometry, whereas abdominal VAT and SAT areas (cm(2)) were measured with
computed tomography. The cardiometabolic risk factors included resting blood
pressure (BP), fasting blood glucose and triglyceride concentrations and high
density lipoprotein cholesterol (HDL-C). RESULTS: Positive relationships across
tertiles of VAT were seen for the participants with high glucose, high BP and low
HDL-C (P<0.043). There was also a significant increase in the percentage of
participants with two or more cardiometabolic risk factors across most tertiles
of abdominal SAT (P<0.042). Logistic regression analysis showed that in
univariate models, all adiposity measures were significantly associated with
increased odds of having all risk factors in men and women. In multivariate
models, VAT was significantly associated with most risk factors across gender.
Abdominal SAT and FM (odds ratios (ORs) 1.3-2.1; all P<0.05) were associated with
fewer risk factors after accounting for VAT. VAT (OR=5.9 and 5.3) and SAT (OR=2.0
and 1.8) were both associated with higher odds of the presence of two or more
cardiometabolic risk factors in both males and females (P<0.001). CONCLUSION: The
data suggest that abdominal SAT is not protective against unfavorable
cardiometabolic risk profiles. These conclusions were consistent across ethnic
groups.
PMID- 23154295
TI - Short- and long-term glucocorticoid treatment enhances insulin signalling in
human subcutaneous adipose tissue.
AB - BACKGROUND: Endogenous or exogenous glucocorticoid (GC) excess (Cushing's
syndrome) is characterized by increased adiposity and insulin resistance.
Although GCs cause global insulin resistance in vivo, we have previously shown
that GCs are able to augment insulin action in human adipose tissue, contrasting
with their action in skeletal muscle. Cushing's syndrome develops following
chronic GC exposure and, in addition, is a state of hyperinsulinemia. OBJECTIVES:
We have therefore compared the impact of short- (24 h) and long-term (7 days) GC
administration on insulin signalling in differentiated human adipocytes in the
presence of low or high concentrations of insulin. RESULTS: Both short- (24 h)
and long-term (7 days) treatment of chub-s7 cells with dexamethasone (Dex) (0.5
MUM) increased insulin-stimulated pTyr612IRS1 and pSer473akt/PKB, consistent with
insulin sensitization. Chronic high-dose insulin treatment induced insulin
resistance in chub-s7 cells. However, treatment with both high-dose insulin and
Dex in combination still caused insulin sensitization. CONCLUSIONS: In this human
subcutaneous adipocyte cell line, prolonged GC exposure, even in the presence of
high insulin concentrations, is able to cause insulin sensitization. We suggest
that this is an important mechanism driving adipogenesis and contributes to the
obese phenotype of patients with Cushing's syndrome.
PMID- 23154296
TI - Effect of trans fatty acid intake on abdominal and liver fat deposition and blood
lipids: a randomized trial in overweight postmenopausal women.
AB - BACKGROUND: Intake of industrially produced trans fatty acids (TFAs) is,
according to observational studies, associated with an increased risk of
cardiovascular disease, but the causal mechanisms have not been fully elucidated.
Besides inducing dyslipidemia, TFA intake is suspected to promote abdominal and
liver fat deposition. OBJECTIVE: We examined the effect of a high intake of TFA
as part of an isocaloric diet on whole-body, abdominal and hepatic fat
deposition, and blood lipids in postmenopausal women. METHODS: In a 16-week
double-blind parallel intervention study, 52 healthy overweight postmenopausal
women were randomized to receive either partially hydrogenated soybean oil
providing 15.7 g day(-1) of TFA or a control oil with mainly oleic and palmitic
acid. Before and after the intervention, body composition was assessed by dual
energy X-ray absorptiometry, abdominal fat by magnetic resonance (MR) imaging,
and liver fat by (1)H MR spectroscopy. RESULTS: Compared with the control fat,
TFA intake decreased plasma high-density lipoprotein (HDL)-cholesterol by 10%,
increased low-density lipoprotein (LDL)-cholesterol by 18% and resulted in an
increased LDL/HDL-cholesterol ratio (baseline adjusted mean (95% CI) difference
between diet groups 0.41 (0.22; 0.60); P<0.001). TFA tended to increase the body
fat (0.46 (-0.20; 1.17) kg; P=0.16) and waist circumference (1.1 (-0.1; 2.4) cm;
P=0.08) more than the control fat, whereas neither abdominal nor liver fat
deposition was affected by TFA. CONCLUSION: The adverse effect of dietary TFA on
cardiovascular disease risk involves induction of dyslipidemia, and perhaps body
fat, whereas weight gain-independent accumulation of ectopic fat could not be
identified as a contributory factor during short-term intake.
PMID- 23154297
TI - Erythrocyte storage duration is not associated with increased mortality in
noncardiac surgical patients: a retrospective analysis of 6,994 patients.
AB - BACKGROUND: More than 5 million patients receive erythrocyte transfusions in the
United States every year. Previous studies linked the storage duration of
allogeneic erythrocytes to the risk of severe postoperative complications,
especially after cardiac or trauma surgery. Limited data are available for
noncardiac surgical patients. We therefore evaluated the association between
storage duration of transfused erythrocytes and postoperative all-cause mortality
among general surgery patients. METHODS: Perioperative data corresponding to
63,319 adult, general surgery patients were obtained from our registry and merged
with blood product data. Patients receiving solely leukocyte-reduced, allogeneic
erythrocyte transfusions were included. Multivariable Cox proportional hazards
regression was used to characterize the relationship between median erythrocyte
storage duration and postoperative mortality rate, adjusting for characteristics
plausibly influencing the storage duration of erythrocytes. RESULTS: Of the 6,994
patients included in the final analysis, 23, 44, 11, 9, and 13% received 1, 2, 3,
4, and >=5 erythrocyte units, respectively. The authors found no evidence that
increasing median storage duration was associated with a difference in the risk
of postoperative mortality (hazard ratio, 0.99 [0.94-1.04]; P = 0.64). Analyzing
the mean storage duration of erythrocyte units as a function of year of
transfusion, the authors demonstrate a relevant decrease in utilization of the
oldest blood units, whereas young blood storage duration remains nearly
unchanged. CONCLUSION: The authors' study supports the recent literature in
surgical and medical patients and underlines the importance of sufficiently
powered randomized trials to finally resolve the erythrocyte storage duration
debate.
PMID- 23154298
TI - Living with a total artificial heart: patients' perspectives.
AB - BACKGROUND: Advances in mechanical circulatory support have reduced morbidity and
mortality in end-stage heart failure. To date, there have been no published
studies examining the psychosocial impact on patients who are supported with a
total artificial heart (TAH-t). PURPOSE: The purpose of this study was to
describe the lived experience of patients currently supported by the TAH-t
awaiting transplant. METHODS: A qualitative method using Giorgi's modification of
phenomenologic inquiry guided the investigation, which was conducted at a
transplant center located in the mid-Atlantic region of the United States. A
purposive sample was selected to reflect participants currently supported by the
TAH-t. All participants (9 men, 1 woman; mean age, 48.2 years; nonischemic
etiology, 80%) were in-patients on the progressive care unit at the time of the
interview and had been supported for at least 30 days. The mean length of device
therapy was 84.7 days (range, 33-245 days). FINDINGS: Hope for the future was the
overarching theme. Subthemes included reflections, for better or for worse, the
secret club, and coping and adaptation. The patients reflected on severity of
illness, progress, and expressed optimism. For better or for worse described how
symptoms improved but were offset by restrictions imposed by the technology. The
secret club described the support provided to help deal with their life
situation. Coping and adaptation suggested that the patients came to terms with
and accepted their circumstances. CONCLUSIONS: The findings will help clinicians
understand patients experiencing a life-changing situation and implications for
psychosocial interventions.
PMID- 23154300
TI - Impact of thyrotropin receptor antibody levels on fetal development in two
successive pregnancies in a woman with Graves' disease.
AB - BACKGROUND: Treatment with radioiodine for Graves' disease regularly increases
the level of antithyroid antibodies, and transplacental passage of stimulating
thyrotropin receptor antibodies (TRAb) may cause fetal hyperthyroidism. CASE
PRESENTATION: A 21-year-old woman with Graves' disease received radioiodine
treatment to avoid use of antithyroid drugs in pregnancy. She became pregnant 4
months later and was euthyroid during pregnancy. In gestational week (GW) 33, she
was admitted with an increased fetal heart rate of 176-180 beats/min. Fetal
echocardiography indicated cardiac decompensation. The neonate had severe
hyperthyroidism (free thyroxine >100 pmol/l, nv 12.0-22.0), cardiac
insufficiency, insufficient weight gain, goiter and considerably accelerated
skeletal age. In the mother and neonate, TRAb was >40 IU/l (nv <1.0), indicating
transplacental passage of stimulating antibodies. After delivery, TRAb remained
>40 IU/l in the woman, and 18 months later she underwent total thyroidectomy with
subsequent decline in TRAb. In her next pregnancy, TRAb fluctuated between 38 and
17 IU/l, and repeated fetal ultrasound showed no goiter or sign of
hyperthyroidism. In cord blood, TRAb was 10.9 IU/l, and the neonate had normal
thyroid hormone levels. CONCLUSION: This case report illustrates the impact of
maternal TRAb level for neonatal outcome in two successive pregnancies.
PMID- 23154299
TI - Improvements in heart rate recovery among women after cardiac rehabilitation
completion.
AB - BACKGROUND: Heart rate recovery (HRR) after exercise cessation is thought to
reflect the rate of reestablishment of parasympathetic tone. Relatively little
research has focused on improved HRR in women after completing cardiac
rehabilitation (CR) exercise training. OBJECTIVE: We examined the influence of
exercise training on HRR in women completing a traditional CR program and in
women completing a CR program tailored for women. METHODS: A 2-group randomized
clinical trial compared HRR between 99 women completing a traditional 12-week CR
program and 137 women completing a tailored CR program. Immediately upon
completion of a symptom-limited graded exercise test, HRR was measured at 1
through 6 minutes. RESULTS: Compared with baseline, improvement in 1-minute HRR
(HRR1) was similar (P = 0.777) between the tailored (mean [SD], 17.5 [11] to 19.1
[12]) and the traditional CR program (15.7 [9.0] to 16.9 [9.5]). The amount of
change in the 2-minute HRR (HRR2) for the tailored (30 [13] to 32.8 [14.6]) and
traditional programs (28.3 [12.8] to 31.2 [13.7]) also was not different (P =
0.391). Similar results were observed for HRR at 3 through 6 minutes. Given these
comparable improvements of the 2 programs, in the full cohort, the factors
independently predictive of post-CR HRR1, in rank order, were baseline HRR1 (part
correlation, 0.35; P < 0.001); peak exercise capacity, estimated as metabolic
equivalents (METs; 0.24, P < 0.001); anxiety (-0.17, P = 0.001); and age (-0.13,
P = 0.016). The factors independently associated with post-CR HRR2 were baseline
HRR2 (0.44, P < 0.001), peak METs (0.21, P < 0.001), and insulin use (-0.10, P =
0.041). CONCLUSIONS: One to 6 minutes after exercise cessation, HRR was
significantly improved among the women completing both CR programs. The
modifiable factors positively associated with HRR1 included peak METs and lower
anxiety, whereas HRR2 was associated with insulin administration and peak METs.
Additional research on HRR after exercise training in women is warranted.
PMID- 23154301
TI - Sensory gating, cannabinoids and schizophrenia.
AB - Sensory gating, a mandatory process in early information processing, has been
found to be defective in neuropsychiatric diseases such as schizophrenia.
Understanding the neurobiology of sensory gating may provide insight into
unravelling the neurobiology of information processing and to yet unanswered
queries on the pathophysiology of disabling neuropsychiatric diseases. The
endocannabinoid system has been linked to the pathophysiology of schizophrenia.
Furthermore, cannabinoids disrupt sensory gating in animals and humans which
supports the hypothesis that the disruption of sensory gating by alterations in
the endocannabinoid system is a significant factor in the etiology of
schizophrenia. Based on the above hypothesis this article reviews the sensory
gating process in relation to the auditory conditioning-test paradigm with an
emphasis on its association with the endocannabinoid system and schizophrenia.
PMID- 23154304
TI - Synthesis of novel indole hydrazone derivatives and evaluation of their
antiplatelet aggregation activity.
AB - Based on the existing reports regarding the antiplatelet aggregation activity of
hydrazone derivatives, a series of indole hydrazone derivatives were considered
as potential antiplatelet agents and synthesized. The structures of the
synthesized compounds were confirmed by spectral data and elemental analysis. The
new indole hydrazone derivatives were evaluated for their ability to inhibit
platelet aggregation induced by adenosine diphosphate (ADP) and arachidonic acid
(AA). Compounds 1h and 3h exhibited remarkable activity against arachidonic acid
induced platelet aggregation with IC(50) values comparable to that of
indomethacin and compound 1i efficiently inhibited platelet aggregation induced
by both ADP and AA.
PMID- 23154302
TI - Combination treatment with progesterone and vitamin D hormone is more effective
than monotherapy in ischemic stroke: the role of BDNF/TrkB/Erk1/2 signaling in
neuroprotection.
AB - We investigated whether combinatorial post-injury treatment with progesterone
(P4) and vitamin D hormone (VDH) would reduce ischemic injury more effectively
than P4 alone in an oxygen glucose deprivation (OGD) model in primary cortical
neurons and in a transient middle cerebral artery occlusion (tMCAO) model in
rats. In the OGD model, P4 and VDH each showed neuroprotection individually, but
combination of the "best" doses did not show substantial efficacy; instead, the
lower dose of VDH in combination with P4 was the most effective. In the tMCAO
model, P4 and VDH were given alone or in combination at different times post
occlusion for 7 days. In vivo data confirmed the in vitro findings and showed
better infarct reduction at day 7 and functional outcomes (at 3, 5 and 7 days
post-occlusion) after combinatorial treatment than when either agent was given
alone. VDH, but not P4, upregulated heme oxygenase-1, suggesting a pathway for
the neuroprotective effects of VDH differing from that of P4. The combination of
P4 and VDH activated brain-derived neurotrophic factor and its specific receptor,
tyrosine kinase receptor-B. Under specific conditions VDH potentiates P4's
neuroprotective efficacy and should be considered as a potential partner of P4 in
a low-cost, safe and effective combinatorial treatment for stroke.
PMID- 23154305
TI - Is it safe to proceed with thrombolytic therapy for acute ischemic stroke in a
patient with cardiac myxoma?.
PMID- 23154306
TI - Sexing frogs by real-time PCR: using aromatase (cyp19) as an early ovarian
differentiation marker.
AB - Most anurans have no identified sex-markers; therefore, alternative methods for
identification of early changes in sex ratios are required. In this study,
Lithobates sylvaticus and Silurana tropicalis tadpoles were sampled at different
developmental stages covering the entire process of sex differentiation. Three
candidate genes known to be involved in sex differentiation in other vertebrate
species were selected to develop a method to identify phenotypic sex in frogs:
cytochrome p450 aromatase (cyp19), forkhead box L2 (foxl2) and the cytochrome 17
alpha-hydroxylase/17,20 lyase (cyp17). Cloning of these genes revealed nucleotide
identity values ranging between 75-97% when compared to other amphibian species.
Gene expression of cyp17,cyp19 and foxl2 in L. sylvaticus adult gonads and gonad
mesonephros complex (GMC) of tadpoles was analyzed by real-time RT-PCR. Results
showed clear sexually dimorphic patterns in the expression of the 3 genes. Our
analysis reveals that GMC gene expression levels of cyp19 alone can be used as a
robust predictor of phenotypic sex in L. sylvaticus tadpoles. In addition, we
validated this method measuring cyp19 mRNA levels in S. tropicalis GMCs. We
propose measuring cyp19 as a tool to study the effects of chemical contaminants
(including endocrine disrupting compounds) on amphibian gonadal development and
sex ratios in the future.
PMID- 23154307
TI - Perinatal periodontal disease reduces social behavior in male offspring.
AB - OBJECTIVE: Our objective was to verify whether prenatal maternal periodontitis is
a risk factor for the development of central nervous system disorders in rats.
METHODS: Periodontitis was induced by placing a ligature around the upper and
lower first molars in 9 female Wistar rats (experimental group); 9 rats were left
unligated (control group). The maternal general activity in an open field was
observed on gestational day (GD) 0, GD 4, and GD 14, and the maternal performance
was assessed on the second day after birth. The pups' play behavior was assessed
on postnatal day 30. The relative level of reelin was measured in the frontal
cortex by real-time PCR analysis. RESULTS: The results showed that, compared with
the control group, (1) the general activity in female rats with periodontitis was
decreased, (2) the maternal performance of these rats was not modified by
periodontitis, (3) the play behavior of pups from dams with periodontitis was
decreased, and (4) there were no differences in the frontal cortex reelin levels
of pups from dams with periodontitis. CONCLUSIONS: We conclude that pre- and
postnatal periodontitis induces maternal sickness behavior and reduces the pups'
play behavior without interference with frontal cortex reelin expression.
PMID- 23154308
TI - Bismuth nanowires with very low lattice thermal conductivity as revealed by the
3omega method.
AB - Thermoelectric materials transform temperature gradients to voltages and vise
versa. Despite their many advantages, devices based on thermoelectric materials
are used today only in a few applications, due to their low efficiency, which is
described by the figure of merit ZT. Theoretical studies predict that scaling
down these materials to the nanometric scale should enhance their efficiency
partially due to a decrease in their lattice thermal conductivity. In this work
we determine for the first time the lattice thermal conductivity of 40 nm bismuth
(Bi) nanowires (NWs), i.e. NWs with a diameter comparable to the Fermi wavelength
of charge carriers in this material. We find a surprisingly low lattice thermal
conductivity of 0.13 +/- 0.05 W K(-1) m(-1) at 77 K. A quantitative argument,
which takes into account several unique properties of Bi, is given to explain
this unusual finding.
PMID- 23154309
TI - Nanomotor-based biocatalytic patterning of helical metal microstructures.
AB - A new nanomotor-based surface-patterning technique based on the movement of a
magnetically powered enzyme-functionalized flexible nanowire swimmer offers the
ability to create complex helical metal microstructures.
PMID- 23154310
TI - Eye on the prize.
PMID- 23154311
TI - SIDATRAT: informatics to improve HIV/AIDS care.
AB - AIDS is a major cause of death in the Caribbean, a region with a high prevalence
of HIV. However, prevalence in Cuba's population aged 15 to 49 years, despite a
slight increase in recent years, is considered extremely low (0.1%). At the close
of 2010, 5692 Cuban patients were receiving antiretroviral therapy. SIDATRAT, an
informatics system, was developed at the Pedro Kouri Tropical Medicine Institute
in Havana to ensure proper monitoring and followup of drug administration.
Functioning on a web platform utilizing an Apache server, PHP and MySQL, it
records patients' general information, CD4 counts, viral load and data from other
laboratory tests, as well as endoscopic and imaging studies. It also compiles
information on their AIDS classification, opportunistic infections, HIV subtype
and resistance studies, followup consultations, drug regimen, adverse reactions
to medications, changes in drug combinations, and survival; and tracks total
number of individuals under treatment. SIDATRAT follows the client-server
philosophy and enables access by authorized users throughout Cuba via the health
informatics network. SIDATRAT has been found effective in supporting quality care
for persons living with HIV/AIDS and universal access to antiretroviral therapy,
compiling most of the information needed for decisionmaking on patient health and
therapies. SIDATRAT has been offered to the UNDP office in Havana for sharing
with other developing countries that may wish to adapt or implement it.
PMID- 23154312
TI - PAHO's presence in Cuban health: Jose Luis Di Fabio PhD. PAHO/WHO representative
in Cuba. Interview by Gail Reed.
PMID- 23154313
TI - Reducing case fatality from acute myocardial infarction in Cienfuegos, Cuba, 1994
2009.
AB - Between 1994 and 2009, the Dr Gustavo Aldereguia University Hospital of
Cienfuegos, Cuba implemented a series of interventions that reduced acute
myocardial infarction case fatality rate from 47% to 15%. These interventions
were part of an institutional plan for myocardial infarction included in the
hospital's overall quality assurance strategy. Outcomes resulted primarily from
organizational changes (from upgrading of the hospital emergency department and
provincial emergency system to creation of a comprehensive coronary care unit and
a chest pain center); optimizing use of effective drugs (streptokinase, aspirin,
ACE inhibitors and beta blockers); adherence to clinical practice guidelines; and
continual and participatory evaluation and adjustment.
PMID- 23154314
TI - Acute myocardial infarction mortality in Cuba, 1999-2008.
AB - INTRODUCTION: Acute myocardial infarction is one of the leading causes of death
in the world. This is also true in Cuba, where no national-level epidemiologic
studies of related mortality have been published in recent years. OBJECTIVE:
Describe acute myocardial infarction mortality in Cuba from 1999 through 2008.
METHODS: A descriptive study was conducted of persons aged >=25 years with a
diagnosis of acute myocardial infarction from 1999 through 2008. Data were
obtained from the Ministry of Public Health's National Statistics Division
database for variables: age; sex; site (out of hospital, in hospital or in
hospital emergency room) and location (jurisdiction) of death. Proportions, age-
and sex-specific rates and age-standardized overall rates per 100,000 population
were calculated and compared over time, using the two five-year time frames
within the study period. RESULTS: A total of 145,808 persons who had suffered
acute myocardial infarction were recorded, 75,512 of whom died, for a case
fatality rate of 51.8% (55.1% in 1999-2003 and 49.7% in 2004-2008). In the first
five-year period, mortality was 98.9 per 100,000 population, falling to 81.8 per
100,000 in the second; most affected were people aged >=75 years and men. Of
Cuba's 14 provinces and special municipality, Havana, Havana City and Camaguey
provinces, and the Isle of Youth Special Municipality showed the highest
mortality; Holguin, Ciego de Avila and Granma provinces the lowest. Out-of
hospital deaths accounted for the greatest proportion of deaths in both five-year
periods (54.8% and 59.2% in 1999-2003 and 2004-2008, respectively). CONCLUSIONS:
Although risk of death from acute myocardial infarction decreased through the
study period, it remains a major health problem in Cuba. A national acute
myocardial infarction case registry is needed. Also required is further research
to help elucidate possible causes of Cuba's high acute myocardial infarction
mortality: cardiovascular risk studies, studies of out-of-hospital mortality and
quality of care assessments for these patients.
PMID- 23154315
TI - Audio computer-assisted self interview compared to traditional interview in an
HIV-related behavioral survey in Vietnam.
AB - INTRODUCTION: Globally, population surveys on HIV/AIDS and other sensitive topics
have been using audio computer-assisted self interview for many years. This
interview technique, however, is still new to Vietnam and little is known about
its application and impact in general population surveys. One plausible
hypothesis is that residents of Vietnam interviewed using this technique may
provide a higher response rate and be more willing to reveal their true behaviors
than if interviewed with traditional methods. OBJECTIVE: This study aims to
compare audio computer-assisted self interview with traditional face-to-face
personal interview and self-administered interview with regard to rates of
refusal and affirmative responses to questions on sensitive topics related to
HIV/AIDS. METHODS: In June 2010, a randomized study was conducted in three cities
(Ha Noi, Da Nan and Can Tho), using a sample of 4049 residents aged 15 to 49
years. Respondents were randomly assigned to one of three interviewing methods:
audio computer-assisted self interview, personal face-to-face interview, and self
administered paper interview. Instead of providing answers directly to
interviewer questions as with traditional methods, audio computer-assisted self
interview respondents read the questions displayed on a laptop screen, while
listening to the questions through audio headphones, then entered responses using
a laptop keyboard. A MySQL database was used for data management and SPSS
statistical package version 18 used for data analysis with bivariate and
multivariate statistical techniques. Rates of high risk behaviors and mean values
of continuous variables were compared for the three data collection methods.
RESULTS: Audio computer-assisted self interview showed advantages over comparison
techniques, achieving lower refusal rates and reporting higher prevalence of some
sensitive and risk behaviors (perhaps indication of more truthful answers).
Premarital sex was reported by 20.4% in the audio computer-assisted self
interview survey group, versus 11.4% in the face-to-face group and 11.1% in the
self-administered paper questionnaire group. The pattern was consistent for both
male and female respondents and in both urban and rural settings. Men in the
audio computer-assisted self-interview group also reported higher levels of high
risk sexual behavior--such as sex with sex workers and a higher average number of
sexual partners--than did women in the same group. Importantly, item refusal
rates on sensitive topics tended to be lower with audio computer-assisted self
interview than with the other two methods. CONCLUSIONS: Combined with existing
data from other countries and previous studies in Vietnam, these findings suggest
that researchers should consider using audio computer-assisted self interview for
future studies of sensitive and stigmatized topics, especially for men.
PMID- 23154316
TI - Clinical impact of RehaCom software for cognitive rehabilitation of patients with
acquired brain injury.
AB - We describe the clinical impact of the RehaCom computerized cognitive training
program instituted in the International Neurological Restoration Center for
rehabilitation of brain injury patients. Fifty patients admitted from 2008
through 2010 were trained over 60 sessions. Attention and memory functions were
assessed with a pre- and post-treatment design, using the Mini-Mental State
Examination, Wechsler Memory Scale and Trail Making Test (Parts A and B).
Negative effects were assessed, including mental fatigue, headache and eye
irritation. The program's clinical usefulness was confirmed, with 100% of
patients showing improved performance in trained functions.
PMID- 23154317
TI - An efficient sampling approach to surveillance of non-communicable disease risk
factors in Cienfuegos, Cuba.
AB - One of the most common shortcomings in non-communicable disease risk factor
surveillance, especially in prevalence studies, is sampling procedures, which can
and do compromise accuracy and reliability of derived estimates. Moreover,
sampling consumes significant time and resources. Since the early 1990s, risk
factor surveys in Cienfuegos province, Cuba have paid particular attention to
careful sampling methods. The new survey conducted in 2011 was not only
statistically rigorous but introduced an innovative, more efficient method. This
article provides a detailed description of the sample design employed to optimize
resource use without compromising selection rigor.
PMID- 23154318
TI - New indicators proposed to assess tuberculosis control and elimination in Cuba.
AB - Following 48 years of successful operation of the National Tuberculosis Control
Program, Cuban health authorities have placed tuberculosis elimination on the
agenda. To this end some tuberculosis control processes and their indicators need
redesigned and new ones introduced, related to: number and proportion of
suspected tuberculosis cases among vulnerable population groups; tuberculosis
suspects with sputum microscopy and culture results useful for diagnosis
(interpretable); and number of identified contacts of reported tuberculosis cases
who were fully investigated. Such new indicators have been validated and
successfully implemented in all provinces (2011-12) and are in the approval
pipeline for generalized use in the National Tuberculosis Control Program. These
indicators complement existing criteria for quality of case detection and support
more comprehensive program performance assessment.
PMID- 23154319
TI - Community engagement, personal responsibility and self help in Cuba's health
system reform.
AB - In 2011 the Cuban health system began a process of sectoral reform to maintain
and improve the health of Cuba's population, in response to new challenges and
demands in the health sector and population health status. The main actions
involved are reorganization, consolidation and regionalization of services and
resources. Although community engagement and personal responsibility are not
explicitly mentioned in the strategy document, it is advisable to use this
opportunity to revitalize both topics and encourage appropriate and full
incorporation into the Cuban health system. Both are consistent with the
objectives and actions of system reforms proposed, in that they allow the various
social actors to assume shared responsibility in working toward social goals--in
this case, health gains. This approach also recognizes that reaching such goals
is a collective endeavor, to be pursued according to ethical principles
(beneficence as responsibility and justice as solidarity), with community
involvement and personal responsibility emerging as two important factors subject
to reorientation in the context of the health system reform under way.
PMID- 23154320
TI - Banishing biases to save lives: introducing genetic testing for familial cancers.
PMID- 23154321
TI - Impaired hypothalamic Fto expression in response to fasting and glucose in obese
mice.
AB - OBJECTIVE: Recent genome-wide association studies have identified a strong
association between obesity and common variants in the fat mass and obesity
associated (FTO) gene. FTO has been detected in the hypothalamus, but little is
known about its regulation in that particular brain structure. The present study
addressed the hypothesis that hypothalamic FTO expression is regulated by
nutrients, specifically by glucose, and that its regulation by nutrients is
impaired in obesity. RESEARCH DESIGN AND METHODS: The effect of intraperitoneal
(i.p.) or intracerebroventricular (i.c.v.) administration of glucose on
hypothalamic Fto mRNA levels was examined in fasted mice. Additionally, the
effect of glucose on Fto mRNA levels was also investigated ex vivo using mouse
hypothalamic explants. Lastly, the effect of i.p. glucose injection on
hypothalamic Fto immunoreactivity and food intake was compared between lean wild
type and obese ob/ob mice. RESULTS: In wild-type mice, fasting reduced both Fto
mRNA levels and the number of Fto-immunoreactive cells in the hypothalamus,
whereas i.p. glucose treatment reversed this effect of fasting. Furthermore,
i.c.v. glucose treatment also increased hypothalamic Fto mRNA levels in fasted
mice. Incubation of hypothalamic explants at high glucose concentration increased
Fto mRNA levels. In ob/ob mice, both fasting and i.p. glucose treatment failed to
alter the number of Fto-immunoreactive cells in the hypothalamus. Glucose-induced
feeding suppression was abolished in ob/ob mice. CONCLUSION: Reduction in
hypothalamic Fto expression after fasting likely arises at least partly from
reduced circulating glucose levels and/or reduced central action of glucose.
Obesity is associated with impairments in glucose-mediated regulation of
hypothalamic Fto expression and anorexia. Hypothalamic Fto-expressing neurons may
have a role in the regulation of metabolism by monitoring metabolic states of the
body.
PMID- 23154322
TI - Primary antiphospholipid syndrome in monozygotic twins.
AB - Monozygotic twins, 27 years old, with primary anti-phospholipid syndrome have
been described. The first of the twins had obstetric morbidities (one miscarriage
at 12 weeks and premature birth of a growth-restricted fetus at 27 weeks
secondary to pre-eclampsia) and the second had venous thrombosis. Lupus
anticoagulant was present in both and anti-cardiolipin antibodies were present in
high titres when re-tested at appropriate intervals. Development of clinical
features of APS in monozygotic twins points to an underlying genetic basis in the
pathogenesis of anti-phospholipid syndrome.
PMID- 23154323
TI - Impact of formulary restriction with prior authorization by an antimicrobial
stewardship program.
AB - In an era of increasing antimicrobial resistance and few antimicrobials in the
developmental pipeline, many institutions have developed antimicrobial
stewardship programs (ASPs) to help implement evidence-based (EB) strategies for
ensuring appropriate utilization of these agents. EB strategies for accomplishing
this include formulary restriction with prior authorization. Potential
limitations to this particular strategy include delays in therapy, prescriber
pushback, and unintended increases in use of un-restricted antimicrobials;
however, our ASP found that implementing prior authorization for select
antimicrobials along with making a significant effort to educate clinicians on
criteria for use ensured more appropriate prescribing of these agents, hopefully
helping to preserve their utility for years to come.
PMID- 23154324
TI - Removing atmospheric turbulence via space-invariant deconvolution.
AB - To correct geometric distortion and reduce space and time-varying blur, a new
approach is proposed in this paper capable of restoring a single high-quality
image from a given image sequence distorted by atmospheric turbulence. This
approach reduces the space and time-varying deblurring problem to a shift
invariant one. It first registers each frame to suppress geometric deformation
through B-spline-based nonrigid registration. Next, a temporal regression process
is carried out to produce an image from the registered frames, which can be
viewed as being convolved with a space invariant near-diffraction-limited blur.
Finally, a blind deconvolution algorithm is implemented to deblur the fused
image, generating a final output. Experiments using real data illustrate that
this approach can effectively alleviate blur and distortions, recover details of
the scene, and significantly improve visual quality.
PMID- 23154325
TI - Detecting motion through dynamic refraction.
AB - Refraction causes random dynamic distortions in atmospheric turbulence and in
views across a water interface. The latter scenario is experienced by submerged
animals seeking to detect prey or avoid predators, which may be airborne or on
land. Man encounters this when surveying a scene by a submarine or divers while
wishing to avoid the use of an attention-drawing periscope. The problem of
inverting random refracted dynamic distortions is difficult, particularly when
some of the objects in the field of view (FOV) are moving. On the other hand, in
many cases, just those moving objects are of interest, as they reveal animal,
human, or machine activity. Furthermore, detecting and tracking these objects
does not necessitate handling the difficult task of complete recovery of the
scene. We show that moving objects can be detected very simply, with low false
positive rates, even when the distortions are very strong and dominate the object
motion. Moreover, the moving object can be detected even if it has zero mean
motion. While the object and distortion motions are random and unknown, they are
mutually independent. This is expressed by a simple motion feature which enables
discrimination of moving object points versus the background.
PMID- 23154326
TI - Annals of plastic surgery issue of the Taiwan Society of Plastic Surgery.
PMID- 23154327
TI - The love surrounding the first skin graft in Taiwan: "British skin" that will
stay in Taiwanese hearts.
AB - There is a painting that looks like a representation of a simple surgical
procedure. However, it holds a warm story of the love surrounding the first skin
graft made by Dr. David Landsborough III for a Taiwanese child in 1928. He
harvested the donor skin from his wife, Marjorie Landsborough, to save a poor
boy. Although the grafted skin could not grow onto the wound, the graft of love
was permanently imprinted on Taiwanese People's hearts. The first Taiwanese
recipient of MD, PhD degree, Dr. Tsung-Ming Tu invited an artist to recreate and
draw the surgical procedure to immortalize the unforgettable love and memory of
Dr. Landsborough III. The painting hanging on the hospital wall portrays an
important professional role model for every student and health care provider. The
life story of this medical missionary in Formosa from 1895 to 1936 contributed
greatly to the development of medical care in Taiwan. It is hoped that this
story, outlining great love and selflessness, can be glorified and remembered for
the world to appreciate for generations to come.
PMID- 23154328
TI - Trismus release in oral cancer patients.
AB - Trismus is a common problem among oral cancer patients. This report aimed to
study the inciting factors of trismus and to find out the rationale of trismus
release. Between 1996 and 2008, 61 oral cancer patients with retrievable records
of interincisor distance (IID) were analyzed by retrospective chart review. The
IID decreased from 31.4 (12.4) to 24.9 (12.0) mm in 36 patients undergoing cancer
ablation only (P = 0.001). Other variables prompting trismus include buccal
cancer (P = 0.017), radiotherapy (P = 0.008), and recurrence (P = 0.001). In
contrast, the IID improved from 11.7 (7.1) to 22.7 (11.9) mm in 25 patients
receiving cancer ablative and trismus releasing surgeries (P = 0.000). The
improvement fared better in individuals with IID less than 15 mm than the others
(P = 0.037). In conclusion, involvement of buccal region, ablative surgery,
radiotherapy, and recurrence are provocative factors of trismus. Patients with
IID less than 15 mm will benefit from releasing surgery significantly. Others may
better be handled with conservative managements firstly, and enrolled as
candidates of surgical release only until the patients entertained a 28-month
period of disease-free interval, by which time the risk of recurrence would be
markedly reduced.
PMID- 23154329
TI - The treatment of bone exposure in burns by using artificial dermis.
AB - BACKGROUND: The treatment of bone-exposed wounds with artificial dermis is not
widely accepted in burn patients because of uncertain clinical results. This
article aimed to review our clinical experience with this technique. METHODS: We
implanted artificial dermis in 11 bone-exposed burns. Implantation was directly
performed on bones with periosteum, whereas bones without periosteum were
trephinated or burred before implantation. All wounds were closed by secondary
skin grafting. RESULTS: The mean patient age was 49 years. Lower extremity is the
most common site of bone exposure. The mean bone exposed area was 55.6 cm,
whereas the mean Integra-implanted area was 86.7 cm. The overall implant take
rate was 91%, and the skin grafting success rate was 80%. No secondary breakdown
was noted after a 2-year follow-up. CONCLUSIONS: This study confirms that
artificial dermis can be an alternative treatment tool for burns with exposed
bones, especially in patients with limited donor sites.
PMID- 23154330
TI - Reconstruction of advance head and neck cancer patients after tumor ablation with
simultaneous multiple free flaps: indications and prognosis.
AB - Simultaneous multiple free flaps have become a useful option in head and neck
reconstructions. We performed a 10-year retrospective study between 2001 and
2010. There were 58 men and 1 woman. The overall mortality rate was 51.7%. The
longest surviving patient is 9 years and 4 months, whereas the shortest surviving
patient was 72 days. The mean survival period was 47.1 (6.8) months. Age (P =
0.755) and tumor size (P = 0.115) did not play a major role, but surgical margin,
lymph node, and tumor recurrence were significant in patient survival with a P
value of 0.026, 0.01, and 0.026, respectively. If wide excision with a margin
that can be free of tumor can be performed, lymph nodes are not involved, and
this is a primary tumor, then time and effort should be spent in a successful
simultaneous multiple free flap reconstruction.
PMID- 23154331
TI - The concept of "two arches" in mandibular reconstruction.
AB - To optimize the outcome of the free fibula flap in mandibular reconstruction, the
central portion of the mandible can be divided into upper and lower arches during
preoperative evaluation and planning. We present 2 cases requiring mandibular
reconstruction with free fibula flap after ameloblastoma excision, to illustrate
the "two arches" concept and its applicability in mandibular reconstruction. The
postoperative course was uneventful. Follow-up at 24 months postoperative
revealed a considerable restoration in facial appearance and provided functional
teeth. Recent advances in mandibular reconstruction could be further refined
through the application of the "two arches" concept. This approach simplifies
surgical planning in selective cases and directs the attention of surgeons to the
specific needs of the 2 distinct regions of the mandible during reconstruction.
PMID- 23154332
TI - Modified tenodesis method for treatment of mallet fractures.
AB - INTRODUCTION: Mallet fractures are avulsions of the terminal extensor tendon from
the base of the distal phalangeal bone with a bony fragment. Surgical treatment,
which provides accurate anatomical reduction and rigid fixation, is recommended
for mallet fractures with involvement of more than one third of the base of the
distal phalangeal bone. Various surgical methods have been reported, but there is
still no standard treatment modality. The purpose of this investigation was to
assess the results of our modified tenodesis method for mallet fractures.
MATERIALS AND METHODS: Using our method, the dorsal fracture fragment was reduced
and fixed to the main part of the distal phalangeal bone by 2 stitches of "figure
of-eight" 4-0 Prolene sutures. We reviewed 12 consecutive patients with 13 mallet
fractures treated with our modified tenodesis method between January 2009 and
March 2012. This retrospective study was composed of 7 male and 5 female
patients, with a mean age of 35.7 years (range, 25-56 years). All patients
underwent surgical treatment and sequent 3-week finger splinting. Patient follow
up lasted 3 to 6 months, with a mean period of 5.2 months. RESULTS: The modified
tenodesis method allowed accurate anatomical reconstruction of the injured
extensor mechanism. Grading by Crawford criteria showed that the outcome was
"excellent" in 8 of 13 digits and "good" in 5 of 13 digits. The follow-up hand x
rays also revealed congruent joint surfaces of distal interphalangeal joints with
no evidence of joint space narrowing. No wound complications were encountered,
and all the patients returned to normal activities without any disability.
CONCLUSIONS: The modified tenodesis method is simple and effective to provide
accurate anatomical reduction and fixation for treatment of type I mallet
fractures. No device penetration of the small bony fragment or pinning through
the distal interphalangeal joint is required, and the surgical complication rate
is low. We recommend this treatment modality for all but chronic cases.
PMID- 23154333
TI - Successful treatment of Kasabach-Merritt phenomenon with intralesional
corticosteroid injections: a case series.
AB - Kasabach-Merritt phenomenon (KMP) is a rare and life-threatening disease of
vascular tumor combined with severe consumptive coagulopathy. Currently, there is
no established effective treatment of KMP. In this case series, from 2006 to
2008, we treated 6 pediatric patients with newly diagnosed KMP using
intralesional corticosteroid injections. The severity and progression of the
disease were closely monitored with clinical photographs, blood sampling, and
tissue biopsies. The 6 pediatric patients (5 females and 1 male) showed tumor
regression after treatments. All coagulopathies were corrected. The average
duration of treatment was 3.8 months. Complete tumor regression was observed at
approximately 3 years. Treatment was complicated in 1 patient with transient
growth retardation. Treatment based on intralesional corticosteroid injections is
effective for pediatric patients with KMP. Treatment-associated complications
seemed to be reversible and acceptable by severity level.
PMID- 23154334
TI - The significance of close but negative excision margin for treatment of soft
tissue sarcoma.
AB - Wide excision is the major recommendation for management of soft-tissue sarcomas.
Pathologic reports of postexcision sarcomas revealed very close (within 2 mm) but
clear excision margins. This investigation was a retrospective study to determine
whether wide reexcision plus radiotherapy (R/T), or R/T only, yielded better
outcomes. MATERIALS AND METHODS: We evaluated our soft-tissue sarcoma cases who
had received wide excision in the past 15 years. The surgical margin conditions
(negative, positive, or close margins) and pathologic status were evaluated. The
different management modalities for each condition were also evaluated
individually and discussed. RESULTS: There were 73 cases from 1995 to 2010 in our
section who had received wide excision. The overall recurrence rate was 24.6%. In
cases with margin positive, the recurrence rate was 20% (2/8) after quick
reexcision. However, the recurrence rate was 56% in patients who received R/T but
without quick reexcision. In cases with close resection margins (<2 mm) with no
reexcision but R/T, the recurrence rate was 45%, and all of them had a high-grade
malignancy sarcoma. The other nonrecurrence cases (55%) had low-grade malignancy
or well-differentiated sarcoma.In summary, in cases with positive margin sarcoma,
quick reexcision plus R/T was suggested and the recurrence rate was relatively
low. In soft-tissue sarcoma cases with close margin, we believe quick reexcision
plus R/T is necessary, especial in high-grade, poor differentiated soft-tissue
sarcomas.
PMID- 23154335
TI - Are auricular keloids and persistent hypertrophic scars resectable? The role of
intrascar excision.
AB - BACKGROUND: Intrascar excision with debulking procedure is a good choice for scar
revision in unique 3-dimensional facial aesthetic units, especially in the
auricular area. It can remove or reduce scars in a shorter course without
distortion of the surrounding anatomic structures and visible operative scars.
This retrospective study was done to present intrascar excision procedures in
persistent auricular hypertrophic scars or keloids. METHODS: Between 1997 and
2010, 18 ears in 13 patient cases with persistent hypertrophic scars and/or
keloids in their external ear due to burns or trauma were collected for
evaluation. There were 10 males and 3 females. The age distributions ranged from
5 to 49 years with an average of 20.1 years. All received intrascar excision with
debulking procedure for their ear deformity. One case combined with YV-plasty
procedure to obtain better aesthetic result. The follow-up period ranged from 0.3
to 14 years with an average of 3.6 years. RESULTS: There was no recurrence in a
series of average 3.6 years follow-up. Of the 13 patients, 11 (84.6%) objectively
presented good and satisfactory surgical outcomes and the other 2 patients were
acceptable. CONCLUSIONS: The intrascar excision in auricular persistent scars or
keloids has the following advantages: it (1) achieves primary closure, (2) does
not distort the anatomic landmarks, (3) does not sacrifice the important
structures, (4) has a debulking effect, (5) can be done anytime, even if scars
are not mature, (6) has good cosmetic results, (7) may combine with Z- or VY
plasty for functional improvement, and (8) has minimal complications.
PMID- 23154336
TI - Expanding the applications of the pedicled anterolateral thigh and vastus
lateralis myocutaneous flaps.
AB - We describe our experience in expanding the use of pedicled anterolateral thigh
and vastus lateralis myocutaneous flaps. A total of 33 patients underwent 34
flaps between March 2003 and January 2012. The defects included 18 ischial, 3
trochanteric, 5 lower abdomen, 2 perineogenital, 1 groin, and 5 knee defects.
There were 29 proximal pedicled (2 of which were preexpanded), 3 distal pedicled,
and 2 propeller flaps. Complications included 1 total necrosis, 1 partial
necrosis, 3 wound dehiscence in recipient site, 1 hematoma, and 1 donor-site
dehiscence. The total flap survival rate was 94%. There were no donor-site
morbidities except poor cosmesis in the skin-grafted sites. Pedicled
anterolateral thigh flap is highly versatile with a wide arc of rotation. A
proximal pedicled flap can be used for lower abdomen, perineogenital, ischial,
and trochanteric defects and the distal pedicled or a propeller flap for knee and
proximal lower leg defects.
PMID- 23154337
TI - The effect of hyperbaric oxygen and air on cartilage tissue engineering.
AB - There is an urgent need to develop tissue-engineered cartilage for patients
experiencing joint malfunction due to insufficient self-repairing capacity of
articular cartilage. The aim of this research was to explore the effect of
hyperbaric oxygen and air on tissue-engineered cartilage formation from human
adipose-derived stem cells seeding on the gelatin/polycaprolactone biocomposites.
The results of histological analyses indicate that under hyperbaric oxygen and
air stimulation, the cell number of chondrocytes in cartilage matrix was not
significantly increased, but the 1,9-dimethylmethylene blue assay showed that the
glycosaminoglycans syntheses markedly increased compared to the control group. In
quantification real-time polymerase chain reaction results, the chondrogenic
specific gene expression of SOX9, aggrecan, and COL2A1 were compared
respectively. Within the limitation of this study, it was concluded that 2.5
atmosphere absolute oxygen and air may provide a stress environment to help
cartilage tissue engineering development.
PMID- 23154338
TI - Adipose-derived stem cells seeded on acellular dermal matrix grafts enhance wound
healing in a murine model of a full-thickness defect.
AB - INTRODUCTION: The promotion of wound healing using dermal substitutes has become
increasingly widespread, but the outcomes of substitute-assisted healing remain
functionally deficient. Adipose-derived stem cells (ASCs) have been investigated
widely in regenerative medicine and tissue engineering, and they have the
potential to enhance wound healing. In this study, we focused on investigating
the effects and mechanism of ASCs combined with an acellular dermal matrix (ADM)
to treat full-thickness cutaneous wounds in a murine model. METHODS: The ADM was
prepared from the dorsal skin of nude mice by decellularization by treatment with
trypsin followed by Triton X-100. The human ASCs were isolated and cultured from
abdominal lipoaspirate. We created a rounded, 8-mm, full-thickness cutaneous
wound in nude mice and divided the mice into the following 4 groups: silicon
sheet cover only, silicon sheet with spreading ASCs, ADM only, and ASCs seeded on
ADM. The granulation thickness was evaluated by histology after 7 days. Further
comparisons between the ADM only and ASC-seeded ADM groups were undertaken by
assessing the reepithelialization ratio and blood vessel density at postoperative
days 9 and 14. Statistical analyses were conducted using Student 2-tailed t test.
Immunofluorescent histology and ASC labeling were also performed to identify
possible mechanisms. RESULTS: The ADM was successfully prepared, and the
cytometry analysis and differentiation assay provided the characterization of the
human ASCs. A marked improvement in granulation thickness was detected in the ADM
ASC group in comparison with other 3 groups. A significantly increased rate of
reepithelialization in the ADM-ASC group (80 +/- 6%) compared to the ADM only
group (60 +/- 7%) was noted on postoperative day 9. The blood vessel density was
evidently increased in the ADM-ASC group (7.79 +/- 0.40 vessels per field)
compared to the ADM only group (5.66 +/- 0.23 vessels) on day 14. Cell tracking
experiments demonstrated that labeled ASCs were colocalized with staining for
VEGF or endothelial cell maker vWF after the transplantation of ADM-ASCs on
postoperative day 14. CONCLUSIONS: Adipose-derived stem cells seeded on an ADM
can enhance wound healing, promote angiogenesis, and contribute to newly formed
vasculature, and VEGF-expressing ASCs can be detected after transplantation. This
model could be used to improve the other clinical applications of ASCs and to
decipher the detailed mechanism by which ASCs interact with wound tissue.
PMID- 23154339
TI - Fabrication of quantum dot-conjugated collagen/hyaluronic acid porous scaffold.
AB - A quantum dot (QD)-conjugated collagen-hyaluronic acid (HA) porous scaffold was
combined with our previously reported animal model of mice inferior epigastric
flaps and QD infusion to study scaffold angiogenesis. A CdSe/ZnS QD-labeled
collagen/HA scaffold was fabricated and examined with a confocal microscope. The
degradation rate of the scaffold was inversely related to 1-ethyl-3-(3
dimethylaminopropyl)carbodiimide concentration used in cross-linking. There was
no cytotoxicity of the QDs as determined by MTT colorimetric assay. Results of
the animal implantation study revealed no difference in acute tissue inflammation
between scaffolds with or without QD labeling. To study scaffold angiogenesis, we
infused the implanted QD-conjugated collagen/HA scaffold with QD of different
fluorescence, which can be simultaneously identified by confocal microscope. By
these evaluations, we conclude that QD-conjugated collagen/HA porous scaffold is
not different from that without conjugation and can be used in our animal model
of scaffold angiogenesis without compromising results.
PMID- 23154340
TI - MicroRNA signatures in ischemia-reperfusion injury.
AB - BACKGROUND: MicroRNAs (miRs) are involved in gene expression and function, but
little is known of their function in ischemia-reperfusion injury (IRI), which
plays a critical role in flap compromise during microvascular flap surgeries.
This article aimed to determine the expression profiles of miRs in rat flap
surgeries after IRI. METHODS: Vessel specimens in rat epigastric flap were
initially determined for miRs survey after 2 hours of ischemia and 2 hours of
reperfusion. Their miR expressions were further quantified after 2 hours of
ischemia and subsequent reperfusion for 2 and 24 hours. RESULTS: Only 3 miRs (miR
21, miR-193-3p, and miR-210) in rat vessels, but not in flap tissues, were
significantly up-regulated at 24 hours of reperfusion after 2 hours of ischemia.
CONCLUSIONS: Our findings provide insights into deregulated expressions of miRs
in flap surgeries after IRI. They might provide a further therapeutic
consideration to prevent vascular compromise due to IRI in flap surgeries.
PMID- 23154341
TI - Herniation of the cervical disk in plastic surgeons.
AB - Herniations of the cervical disk in plastic surgeons are far more common in
practice than the paucity of reported cases would indicate. A likely explanation
may be the peculiar, nonergonomic positions that plastic surgeons must hold
during surgery while wearing a headlight and loupes. From January 2003 to
December 2006, at Tri-Service General Hospital, Taiwan, 4 plastic surgeons
experienced herniations of the cervical disk. Magnetic resonance imaging study
indicated there was disk herniation or bulging with spinal cord impingement. Two
plastic surgeons received cervical diskectomy, corpectomy with strut
reconstruction using titanium cages. These 2 surgeons were symptom-free 2 years
after their operations. The other 2 plastic surgeons were under conservative
physical therapy with persistent symptoms. The clinical evidence indicated that
cervical disk herniation is an occupational hazard in plastic surgeons. To
prevent prolonged hyperflexion and twisting of the neck, we proposed wearing a
cervical brace during surgery for the plastic surgeons at Tri-Service-General
Hospital since January 2008. No more plastic surgeons have experienced herniation
of the cervical disk since then. The results indicated that wearing a cervical
brace may be an effective measure to protect plastic surgeons from cervical disk
disease.
PMID- 23154342
TI - Mold attacks a beating heart.
PMID- 23154343
TI - The core teams concept in craniofacial surgery from the start.
PMID- 23154344
TI - Management of decompressive craniectomy defects: modern military treatment
strategies.
AB - BACKGROUND: Decompressive craniectomy has become a critical and standard life
saving maneuver in the theater of war. The high number of patients returning with
large cranial defects and complex craniofacial injuries often involving the upper
orbits or associated with the sunken skin flaps are a reconstructive challenge.
We present a review of our treatment protocol highlighting the evolution of
decompressive craniectomy and the development of a modern cranial defect
treatment algorithmic approach to reconstruct these difficult clinical cases.
METHODS: A review of previously published data and current data from our warfare
treatment unit that reported the treatment of decompressive cranial defects from
2004 to 2011 was performed. Reported data included mechanism of injury,
evacuation time, initial Glasgow Coma Scale (GCS), GCS on arrival to the
continental United States, type of decompressive craniectomy, type of implants
used for reconstruction, and complications such as implant infections, exposures,
and removals. Secondary reconstruction techniques used to salvage failed
cranioplasty cases with free tissue transfers and cranial bone or dermal fat
grafts as indicated were also reviewed and outcomes were reported. RESULTS: From
March 2003 to July 2011, more than 200 patients were identified who underwent
cranioplasty after decompressive craniectomy. Patient average age was
approximately 25 years (range, 18-53 y), and all patients were male. Average
follow-up was 870 days (2.4 y). Average GCS at initial presentation was 7 and was
9 on arrival to the continental United States. Average time to evacuation to the
continental United States was 6 days. Of all injuries, 46% were associated with
an improvised explosive device blast. Of the patients, 90% underwent
hemicraniectomies with the remaining 10% having received bifrontal craniectomies.
Successful reconstruction and retention of the implant was present in 95% of the
overall cohort. Contour abnormalities were the most common adverse outcome
encountered (10% of patients after cranioplasty), whereas infections resulting in
implant loss (5%) and seizures (<5%) were the most common complications that
occurred after cranioplasty reconstruction. CONCLUSIONS: Warfare-related
decompressive craniectomy defects can be safely reconstructed using custom
alloplastic implants with low morbidity and mortality. Risk factors that increase
the rate of infection and require implant removal included orbital extension of
the craniectomy defect, proximity to facial sinuses, and large contour
abnormalities with corresponding large dead spaces. Staging reconstruction of
high-risk cranial defects followed by definitive cranial defect reconstruction
improved the likelihood of implant retention and successful cranioplasty outcome.
PMID- 23154345
TI - My time with Henry: 40+ years together.
PMID- 23154346
TI - The Venetian blind technique: modification of the Pi procedure for the surgical
correction of sagittal synostosis.
AB - Numerous methods of surgical repair for scaphocephaly (sagittal synostosis) have
been reported in the literature, from strip craniectomies to more complex methods
of calvarial vault remodeling. While good cosmesis and restoration of a normal
anteroposterior diameter may be obtained with these methods, a more rounded
contour of the biparietal areas is often more difficult to achieve. We describe a
modification of the Pi technique, described by Jane in 1976, that results in a
more rounded contour of the biparietal areas. We report our experience on cranial
vault remodeling for the correction of scaphocephaly in 51 patients from 1998 to
2011.
PMID- 23154347
TI - Craniofacial surgery on a personal view.
AB - Henry Kawamoto Jr and I go back a long way. Our friendship began at the Columbia
Presbyterian Medical Center. I had just returned from my service obligation after
interrupting my general surgery residency. I heard that a new resident from
California had been admitted to our class, and, of course, it was Henry.
PMID- 23154348
TI - Microsurgical correction of progressive facial hemiatrophy using free
anterolateral thigh adipofascial flap.
AB - BACKGROUND: The etiology of progressive facial hemiatrophy is unclear according
to resent research. The diseases lack effective treatments. The purpose of this
study was to introduce a technique that restores the cosmetic amelioration
effectively using free anterolateral thigh adipofascial flap through anastomosis.
METHODS: From September 1999 to June 2011, a total of 14 patients were subjected
to correction with revascularized free anterolateral thigh adipofascial flaps at
the first stage. Some of them performed additional procedures, such as dermal fat
flap filling, lipoinjection, liposuction, and thinning of the flap, were used for
secondary minor deformities after the first-stage operation. The donor sites were
closed primarily without skin grafting or other flap transplantation. RESULTS:
All of the flaps survived, and the effect is stable during the follow-ups.
Patients were quite satisfied with the symmetry and plumpness of the
reconstructed faces. The donor sites were sutured directly and healed at the
first stage; there were no obvious morbidities and dysfunctions. CONCLUSIONS: The
anterolateral thigh adipofascial flap can provide adequate tissue with reliable
blood supply, pliability, ease of revision, and minimal morbidity and dysfunction
at the donor site. It is a safe, stable, and effective technique for hemifacial
atrophy.
PMID- 23154349
TI - Endoscopic delivery of calcium phosphate cement for secondary craniofacial
reconstruction.
AB - Contour defects are common following primary craniofacial procedures including
cranial vault remodeling, fronto-orbital and midface advancements, and complex
posttraumatic reconstructions. When onlayed as fast-setting pastes, calcium
phosphate cements (CPCs) have been used to effectively correct contour defects in
open secondary reconstruction procedures. Here, we describe an endoscopic
procedure using an injectable CPC and compare surgical outcomes with the open
technique. A retrospective review was conducted for 36 consecutive patients aged
3.0-28.9 years (mean, 10.1 years) who underwent secondary craniofacial
reconstruction over a 3-year period. Patients were stratified into endoscopic or
open groups depending on the surgical approach utilized. Mean operative time was
significantly shorter (P < 0.001) for the endoscopic group (64 minutes) than for
the open group (131 minutes). Similarly, hospital stay was significantly shorter
(P = 0.005) in the endoscopic group than in the open group. There was also a
significant difference with respect to cost (P < 0.001), with the endoscopic
approach resulting in a per-patient cost savings of $2208.05. In conclusion,
endoscopic delivery of CPC appears to be a safe, efficacious, and cost-effective
method of performing secondary craniofacial reconstruction, with the additional
benefits of decreased operative time and shorter postoperative hospital stay when
compared with an open procedure.
PMID- 23154350
TI - Nonsyndromic craniosynostosis: the Rady Children's Hospital approach.
AB - ABSTRACT: Surgical correction for nonsyndromic craniosynostosis has continued to
evolve over the last century. The criterion standard has remained open correction
of the cranial deformities, and many techniques have been described that yield
satisfactory results. However, technology has allowed for minimally invasive
techniques to be developed with the aid of endoscopic visualization. With proper
patient selection and the aid of postoperative helmet therapy, there is
increasing evidence that supports these techniques' safety and efficacy. In this
article, our purpose was to describe our algorithm for treating nonsyndromic
craniosynostosis at Rady Children's Hospital.
PMID- 23154352
TI - Commentary on "Nonsyndromic craniosynostosis: the Rady Children's Hospital
approach".
PMID- 23154351
TI - Models of cranial suture biology.
AB - Craniosynostosis is a common congenital defect caused by premature fusion of
cranial sutures. The severe morphologic abnormalities and cognitive deficits
resulting from craniosynostosis and the potential morbidity of surgical
correction espouse the need for a deeper understanding of the complex etiology
for this condition. Work in animal models for the past 20 years has been pivotal
in advancing our understanding of normal suture biology and elucidating
pathologic disease mechanisms. This article provides an overview of milestone
studies in suture development, embryonic origins, and signaling mechanisms from
an array of animal models including transgenic mice, rats, rabbits, fetal sheep,
zebrafish, and frogs. This work contributes to an ongoing effort toward continued
development of novel treatment strategies.
PMID- 23154353
TI - Pierre Robin sequence and Treacher Collins hypoplastic mandible comparison using
three-dimensional morphometric analysis.
AB - Pierre Robin sequence and Treacher Collins syndrome are both associated with
mandibular hypoplasia. It has been hypothesized, however, that the mandible may
be differentially affected. The purpose of this study was to therefore compare
mandibular morphology in children with Pierre Robin sequence with children with
Treacher Collins syndrome using three-dimensional analysis of computed
tomographic scans. A retrospective analysis was performed identifying children
with Pierre Robin sequence and Treacher Collins syndrome undergoing computed
tomography. Three-dimensional reconstruction was performed, and ramus height,
mandibular body length, and gonial angle were measured. These were then compared
with those in control children with normal mandibles and with the clinical norms
corrected for age and sex based on previously published measurements. Mandibular
body length was found to be significantly shorter for children with Pierre Robin
sequence, whereas ramus height was significantly shorter for children with
Treacher Collins syndrome. This resulted in distinctly different ramus height
mandibular body length ratios. In addition, the gonial angle was more obtuse in
both the Pierre Robin sequence and Treacher Collins syndrome groups compared with
the controls. Three-dimensional mandibular morphometric analysis in patients with
Pierre Robin sequence and Treacher Collins syndrome thus revealed distinctly
different patterns of mandibular hypoplasia relative to normal controls. These
findings underscore distinct considerations that must be made in surgical
planning for reconstruction.
PMID- 23154354
TI - A personal tribute to a great educator: how Henry Kawamoto influenced my interest
in facial soft tissue anatomy and changed my plastic surgery career.
AB - Henry Kawamoto remains one of the most influential craniofacial surgeons of the
20th century. A Tessier-trained craniofacial surgeon, Dr. Kawamoto has personally
influenced not only the lives of his patients, but significantly also the lives
of those craniofacial fellows he educated, passing on the Tessier methodology to
future generations. This article serves as an anecdote as to how Dr. Kawamoto's
mentoring influenced a personal understanding of facial soft tissue anatomy,
leading to improved technical approaches for surgical rejuvenation of the aging
face.
PMID- 23154355
TI - Le Fort II osteotomy.
AB - BACKGROUND: In comparison with the abundant literature on Le Fort I and III
osteotomies, there is scant information on the Le Fort II osteotomy. Our goal in
this study was to define the indications and techniques of the elective Le Fort
II osteotomy. We reviewed our 30-year experience, which is the longest series of
patients treated with Le Fort II osteotomies at a single institution. METHODS: A
review of the records of 13 consecutive patients at our institution with a
diagnosis of Le Fort II was conducted. Data analyzed included demographic
information, indications, techniques, complications, and combined procedures. On
the basis of surgical outcomes, a treatment algorithm was created. RESULTS:
Thirteen patients had a diagnosis of Le Fort II at our institution. Five were
excluded because of incomplete records or Le Fort II fracture repair. Three
patients were male, and 5 were female. Their average age was 23 years, and the
average follow-up was 60 months. Indications included nasomaxillary deviation
related to unilateral coronal synostosis, hemifacial microsomia, Romberg disease,
and noncleft nasomaxillary hypoplasia. The average estimated blood loss was 950
mL. Complications were persistent nasal deviation, temporary nasal obstruction,
and a hematoma. Complementary procedures included bilateral sagittal split
osteotomies, bone grafts, Le Fort I osteotomy, and repositioning of the zygoma.
CONCLUSIONS: On the basis of this review, we have elucidated the indications and
less invasive techniques of the elective Le Fort II osteotomy. No major
complications were observed. A management algorithm for performing the Le Fort II
osteotomy is presented.
PMID- 23154356
TI - Commentary on "Le Fort II osteotomy".
PMID- 23154357
TI - Parry-Romberg reconstruction: optimal timing for hard and soft tissue procedures.
AB - For the treatment of Parry-Romberg syndrome or progressive hemifacial atrophy, we
studied 3 controversial issues: (1) optimal timing, (2) need for skeletal
reconstruction, and (3) need for soft tissue (medial canthus/lacrimal duct)
reconstruction. Patients with Parry-Romberg syndrome (>5 y follow-up) were
divided into 2 groups: (1) younger than 14 years and (2) 14 years or older (n =
43). Sex, age, severity of deformity, number of procedures, operative times, and
augmentation fat volumes were recorded. Physician and patient satisfaction
surveys (5-point scale) were obtained, preoperative and postoperative three
dimensional computed tomographic scans were reviewed, and a digital three
dimensional photogrammetry system was used to determine volume retention. Our
results indicate that the younger patient group required more procedures compared
with the older patient group (4.3 versus 2.8); however, the younger group had
higher patient/family satisfaction scores (3.8 versus 3.0). Skeletal and soft
tissue reconstruction resulted in improved symmetry score (60% preoperatively to
93% final) and satisfaction scores (3.4 preoperatively to 3.8 final). Patients
with Parry-Romberg syndrome required multiple corrective surgeries but showed
improvements even when beginning before puberty. Soft and hard tissue
reconstruction was beneficial.
PMID- 23154358
TI - Obstructive sleep apnea after dynamic sphincter pharyngoplasty.
AB - INTRODUCTION: In patients who require additional surgery for velopharyngeal
insufficiency (VPI), a higher incidence of obstructive sleep apnea (OSA) may be
incurred. Although this phenomenon has been demonstrated with the posterior
pharyngeal flap, the effect of dynamic sphincter pharyngoplasty (DSP) on OSA is
less clear. The purposes of this case series were to (1) determine the incidence
of OSA after DSP, (2) assess the changes in polysomnography after DSP, and (3)
identify risk factors for the development of OSA after DSP. Our global hypothesis
is that OSA and VPI exist on a continuum and that speech outcomes should not be
considered in isolation. METHODS: For a 13-year period, 146 patients with
idiopathic VPI, submucous cleft palate, cleft palate only, or cleft lip and
palate underwent DSP for VPI. The diagnosis of OSA was defined as the
prescription of continuous positive airway pressure therapy by a pediatric sleep
medicine physician. The incidence of OSA preoperatively and postoperatively was
compared using Fisher exact test. When available, preoperative and postoperative
apnea-hypopnea indices (AHIs) were compared using the pairwise, 2-tailed,
Student's t-test. Patient factors, such as obesity (body mass index >= 95th
percentile), the presence of a craniofacial syndrome, surgical history, and a
preexisting OSA diagnosis, were noted. A multiple logistic regression was
performed to elucidate risk factors for the development of OSA. RESULTS: The
average age at surgery was 9.2 years (range, 4-40 y), and the mean follow-up time
was 4.5 years (range, 1 mo to 12 y). The incidence of OSA increased after DSP,
from 2 to 33 patients (1.4%-22%, respectively; P = 0.05). In 23 patients (16%),
both preoperative and postoperative AHIs were available. There was a significant
increase in AHI after DSP, from 3.1 to 8.4 episodes per hour of sleep (P =
0.001). Previous tonsillectomy/adenoidectomy was predictive of OSA after DSP
(relative risk = 2.4; P = 0.04). CONCLUSIONS: We report an increased incidence of
OSA and higher-than-average AHIs postoperatively after DSP. Preoperative
tonsillectomy/adenoidectomy predicted the development of OSA after DSP. A high
index of suspicion for development of OSA must be maintained in patients who
undergo secondary speech operations for VPI. Clinical screening for OSA should be
used in this population, with a low threshold for polysomnographic evaluation.
The surgeon must be wary that improvements in speech after DSP may change airway
dynamics and increase the risk of OSA.
PMID- 23154359
TI - Commentary on "Obstructive sleep apnea after dynamic sphincter pharyngoplasty".
PMID- 23154360
TI - Thoughts on the Davies repair of unilateral cleft lip.
AB - The Davies Z-plasty repair of the unilateral cleft lip can generate adequate lip
height with little transverse tightness and should be considered in the presence
of a vertically short lateral lip. Separate repair of the orbicularis muscle may
contribute to good long-term lip height and shape. It is possible to revise the Z
repair to increase height.
PMID- 23154361
TI - Immediate mandibular distraction in mandibular hypoplasia and upper airway
obstruction.
AB - Distraction osteogenesis of the mandible has become an alternative to
tracheostomy in infants and children who present with upper airway obstruction
due to micrognathia. To avoid prolonged intubation during distraction, we have
implemented a protocol of immediate distraction at the time of distractor
placement, which results in acute airway improvement. Over 2 years, 22 patients
with micrognathia and severe airway obstruction have undergone mandibular
distractor placement. Indications for surgery were apnea and desaturations with
feeding. Resorbable distraction devices were placed bilaterally and activated to
5 to 8 mm. Recombinant human bone morphogenetic protein 2 was placed in the gap.
Distraction was implemented at postoperative day 2 at 2 mm/d. Forty-four
distraction devices were placed in 22 patients (68% male, 32% female) with a mean
age of 24.1 months (range, 3 days to 5.5 years). The average distance of
distraction performed in the operating room was 5 mm. The average total
distraction was 24 mm performed over 12 days. Overall, 89% of patients were
extubated after distractor placement in the operating room. Two patients with
difficult intubations were extubated 7 days later in the operating room with
otolaryngology. Of the 4 tracheostomy patients, 1 patient was decannulated,
whereas 3 patients are pending postoperative sleep studies. One patient had a
minor wound complication. Tracheostomy and prolonged intubation in patients with
mandibular hypoplasia have significant morbidity and mortality. We have
implemented a successful protocol of immediate distraction in the operating room
with placement of bone morphogenetic protein. Immediate distraction appears to be
an effective method of avoiding postoperative intubation and tracheostomy.
PMID- 23154362
TI - Valuing and selling a practice.
AB - Surgeons, as they contemplate retirement, wrongly believe that their practices do
not have financial value. In fact, a well-organized efficiently functioning
office with an emphasis on excellent service in combination with a constant
stream of patients make it financially ideal for the new surgeon. Being able to
assume such a practice can be a very smart financial decision. The practice's
worth can be determined by a careful analysis of the practice financials and an
evaluation of the functioning of the office and employees. Purchasing such a
practice can be, economically, a very smart move by a new surgeon. Payments are
made over time at a rate that allows the surgeon to make a good living, leaving
him with real equity once the payments are complete. The departing surgeon, who
had spent years building this successful practice, gets some of this value back
in the form of an income stream to supplement his retirement. This process should
be considered in virtually every case. Do not just "close the door."
PMID- 23154364
TI - Commentary on "Incisions for orbital floor exploration".
PMID- 23154363
TI - Incisions for orbital floor exploration.
AB - Incisions used for orbital floor exploration continues to remain a topic of
controversy. Historically, 3 incisions have been used for orbital floor repair:
transconjunctival, subciliary, and subtarsal. Past studies have attempted to
stratify the superiority of one incision over the others. Insufficient level of
evidence and inconsistent methodology have lead to inconclusive data. Our authors
performed a systematic review of literature to assess the quality of evidence in
literature and recommend guidelines for incisions for repairing orbital
fractures. Thirty-one articles were identified, comprising a total of 4688
incisions. Technique along with individual benefits and complication profiles for
each incision is reviewed. Objectivity and follow-up time intervals are necessary
parameters for evaluating incisions for orbital floor exploration to further
define guidelines.
PMID- 23154365
TI - Materials used for reconstruction after orbital floor fracture.
AB - Advances in biotechnology continue to introduce new materials for reconstruction
of orbital floor fractures. Which material is best fit for orbital floor
reconstruction has been a controversial topic. Individual surgeon preferences
have been supported by inconsistent inconclusive data. The purpose of this study
was to assess and analyze published evidence supporting various materials used
for orbital floor reconstruction and to develop a decision-making algorithm for
clinical application. A systematic literature review was performed from which 48
studies were selected after primary and secondary screening based on set
inclusion and exclusion criteria. This cumulatively included 3475 separate
orbital floor reconstructions. Results revealed risk and benefit profiles for all
materials. Autologous calvarial bone grafts, porous polyethylene, and
polydioxanone (PDS) were most widely used for orbital floor reconstruction.
Increased infection rates were reported with polyglactin 910/PDS composites and
silastic rubber. Ocular motility was reduced most with lyophilized dura and PDS.
Preoperative and postoperative rates for diplopia and enophthalmos varied among
the materials. In conclusion, our results revealed continued inadequate evidence
to exclusively support the use of any one biomaterial/implant for orbital floor
reconstruction. Results have served to create a decision-making algorithm for
clinical application. Our authors propose certain parameters for future studies
seeking to demonstrate a comparison between 2 or more materials for orbital floor
reconstruction.
PMID- 23154366
TI - More to this study than meets the eye.
PMID- 23154367
TI - The Kawamoto epilogue: a prologue for craniofacial surgery.
PMID- 23154368
TI - Vector control in internal midface distraction using temporary anchorage devices.
AB - Le Fort III and monobloc distraction osteogenesis serve as the primary surgical
treatment for children with severe midface hypoplasia. The orbital retrusion and
class III malocclusion of patients with midface hypoplasia is best addressed with
bodily advancement of the midface segment parallel to the cephalometric Frankfort
horizontal plane. Use of internal distraction devices allows for advancement of
the midface without extensive external hardware but comes at the cost of less
vectorial control, resulting in a distraction vector that can cause a clockwise
rotation of the entire midface or frontofacial component creating hollow
appearing orbits. To counteract this clockwise rotation, we have developed a
technique using orthodontic microimplants to anchor interarch class III
relationship elastics. We report our experiences with this technique on a
cadaveric model and as a case series of 17 patients who underwent midface
distraction. A Le Fort III distraction procedure was carried out on a cadaver,
and the orbital height was measured at 0-, 10-, and 20-mm distraction advancement
with and without elastics in a class III relationship. Improvement of both
subjective hollow appearance of the orbits and objective measurement of the
orbital height with class III relationship elastics demonstrated the efficacy of
class III relationship elastics in counteracting the clockwise rotation of the
midface segment. A review of 17 patients with midface or frontofacial hypoplasia
treated with Le Fort III or monobloc distraction with simultaneous microimplant
anchored class III relationship elastics revealed correction of malocclusion and
improved midface projection without significant increase in vertical height of
the orbits.
PMID- 23154369
TI - What K would do.
PMID- 23154370
TI - Separation of craniopagus conjoined twins with a staged approach.
AB - The separation of craniopagus conjoined twins is a very rare and complex
challenge. As with many rare challenges, it presents initially as a deceptively
simple problem requiring only the most basic clinical techniques. As in many
reconstructive problems, this paradigm mandates that the neurosurgical team
performs the separation with the plastic surgeons providing closure at the end of
the separation. Historically, these approaches have included, as with the
separation of many other types of conjoined twins, the use of tissue expansion
before separation followed by separation surgery. In the best hands, at the most
capable medical centers, the mortality reported in the literature for the past 50
years is greater than 50%. Craniofacial surgery frequently demands a coordinated
effort between plastic surgery and neurosurgery and many other specializations;
separating craniopagus twins takes this coordination to a stratospheric level. It
is, however, this coordination that is of paramount importance. Success clearly
requires an understanding of the complex interrelationship between the
"separation" and the "reconstruction" and that decisions made for 1 aspect of the
surgery will have a profound impact on another aspect of the surgery. The impact
can be disastrous or, if planned well, can be advantageous.We were contacted to
evaluate craniopagus conjoined male infant twins for separation. Radiographic
studies suggested that the brains were separate, and their medical team suggested
that they were "fit for separation." We reviewed the literature and reviewed our
colleagues' experiences with similar cases around the world. It became clear that
whether separation had been unsuccessful or successful, a variety of issues
accompanied surgery as follows: (1) massive intraoperative hemorrhage, (2)
cerebral edema, (3) venous infarcts, (4) swelling of flaps, and (5) dehiscence of
repairs with cerebrospinal fluid (CSF) leak, meningitis, or brain exposure.
Although the initial plan was to separate the twins in the same fashion as in
previous cases (ie, single-stage separation surgery preceded by tissue expansion
of the scalp), it was clear that this approach increases cerebral venous pressure
during the separation component of surgery and therefore set up a cascade of
events favoring failure rather than success. Wishing to favor success, we elected
to design an open-ended multistaged separation to improve venous collateral
circulation. We believe that this would improve venous drainage, prevent
increased venous pressure, diminish cerebral edema, and favor the integrity of
the dura and flap repair that would in turn lessen the risk of CSF leak. The
stages would also allow the twins to recover from each stage before progressing
to the next stage while continuing to receive nutritional support and physical
therapy. Four major stages for 9 1/2 months led to their successful separation.
There has been no CSF leak or meningitis. To our knowledge, this technique has
since been applied to 2 other sets of craniopagus with similar outcomes.A review
of the pertinent literature, our rationale, and methodology are discussed in this
article.
PMID- 23154371
TI - Transient oblong anisocoria and orbital surgery.
AB - We present a rare case of transient oblong (segmental) anisocoria occurring at
the time of limited orbital surgery. Observation of this previously undescribed
phenomenon prompted us to review the relevant anatomy and physiology of the iris
and the pharmacokinetics of lidocaine as it pertains to surgery in the region of
the eyelids and the orbit.
PMID- 23154372
TI - Commentary on "Transient oblong anisocoria and orbital surgery".
PMID- 23154373
TI - Bregmatic wormian bone and metopic synostosis.
AB - We present a case of a 14-week-old girl with metopic synostosis and an incidental
finding of a large, pentagonal bregmatic wormian bone. No prior photographic
evidence of this combination of rare findings exists. An extensive review of the
incidence, etiology, and significance of these unusual supernumerary cranial
bones is provided in this study.
PMID- 23154374
TI - Photoelastic analysis of stresses transmitted by universal cast to long abutment
on implant-supported single restorations under static occlusal loads.
AB - OBJECTIVES: The aim of this study was to compare the stresses resulting from
cemented or screw-retained dental prostheses using universal cast to long
abutment by the photoelastic method. MATERIAL AND METHODS: A photoelastic resin
model was fabricated to simulate a segment of the mandibular arch with resin
replicas of a first premolar and a second molar, and two 3.75 * 11-mm implants
replacing the second premolar and the first molar. Vertical static loads were
individually applied on the occlusal surface of the premolar and the molar (5
kgf) and simultaneously on both crowns (10 kgf). RESULTS: Results found variable
stress patterns around each implant and concentrated stresses in the individually
loaded crowns. Force transfer characteristics of each situation and
quantification of the isochromatic fringes were evaluated. CONCLUSIONS: Within
the limitations of this study and based on the results obtained for implant
supported prosthesis with internal hexagon connection/universal cast to long
abutment, it could be concluded that single adjacent screw-retained prosthetic
restorations lead to higher stresses around the implants when compared with
cement-retained restorations.
PMID- 23154375
TI - Humanitarian cleft care in Southeast Asia: military-civilian partnerships and the
role of the US Navy ship Mercy.
AB - The primary mission of the US Navy (USN) is to maintain superior naval forces
capable of winning wars, deterring aggression, and maintaining freedom of the
seas. However, a major core capability of the present-day USN includes the
ability to effectively and rapidly provide humanitarian assistance and disaster
response whenever the need arises. Occurring annually since 2006, Pacific
Partnership is an ongoing USN operation that aims to strengthen regional
alliances and improve delivery of humanitarian assistance and disaster relief. A
major focus of Pacific Partnership 2010 was the delivery of medical care to
underserved communities in the region. A significant portion of the medical
mission was specifically directed toward the treatment of patients with cleft lip
and palate. As the main operational platform, the USN Ship Mercy provided an
unparalleled environment in which to provide state-of-the-art multidisciplinary
treatment to patients with cleft lip and palate. With the cooperation of host
nations and locally active nongovernmental organizations, a sustainable model for
providing treatment for cleft lip and palate can be developed.
PMID- 23154376
TI - Soft tissue correction of craniofacial microsomia and progressive hemifacial
atrophy.
AB - BACKGROUND: Moderate to severe soft tissue deficits can exist with craniofacial
microsomia or progressive hemifacial atrophy. The authors reviewed the surgical
correction of these defects, including serial autologous fat grafting and
parascapular free tissue transfer. METHODS: Recently treated patients at the
Institute of Reconstructive Plastic Surgery at NYU Medical Center were
identified. Patients with microvascular free flap underwent reconstruction with
parascapular flaps. These flaps have been modified from previously reported
inframammary extended circumflex scapular flaps. Demographic information,
operative interventions, complications, and outcomes were reviewed and analyzed.
The clinical outcomes of these patients were compared with previously reported
patients who underwent serial autologous fat grafting. RESULTS: Five patients
were recently treated with 7 parascapular flaps. The mean age of the patients at
the time of parascapular flap reconstruction was 13.1 years. These were compared
to those previously reported who have undergone serial autologous fat grafting.
The mean number of procedures was less for the free tissue transfer cohort. There
were no microvascular complications because all free flaps survived. One patient
had wound dehiscence of the donor site managed with local wound care and healing
by secondary intention. CONCLUSIONS: For patients undergoing multiple-stage
reconstruction of craniofacial microsomia, serial fat grafting is a useful tool
for soft tissue reconstruction. Alternatively, in those patients with isolated
soft tissue hypoplasia, such as progressive hemifacial atrophy, microvascular
free tissue transfer is a safe and efficient option.
PMID- 23154377
TI - Accelerating surgical training and reducing the burden of surgical disease in
Haiti before and after the earthquake.
AB - In general, university-based global health initiatives have tended to focus on
expanding access to primary care. In the past, surgical programs may have been
characterized by sporadic participation with little educational focus. However,
there have been some notable exceptions with plastic surgery volunteer missions.
We offer another model of regularly scheduled surgical trips to rural Haiti in
plastic and general surgery. The goal of these trips is to reduce the burden of
surgical disease and ultimately repair every cleft lip/palate in Haiti. Another
principal objective is to accelerate the training of American residents through
increased case load and personal interaction with attending surgeons in a
concentrated period. Diversity of the case load and the overall number of
surgeries performed by residents in a typical surgical trip outpaces the
experiences available during a typical week in an American hospital setting. More
importantly, we continue to provide ongoing training to Haitian nurses and
surgeons in surgical techniques and postoperative care. Our postoperative
complication rate has been relatively low. Our follow-up rates have been lower
than 70% despite intensive attempts to maintain continued communication with our
patients. Through our experiences in surgical care in rural Haiti, we were able
to quickly ramp up our trauma and orthopedic surgical care immediately after the
earthquake. Project Medishare and the University of Miami continue to operate a
trauma and acute care hospital in Port au Prince. The hospital provides ongoing
orthopedic, trauma, and neurosurgical expertise from the rotating teams of
American surgeons and training of Haitian surgeons in modern surgical techniques.
We believe that surgical residencies in the United States can improve their
training programs and reduce global surgical burden of disease through consistent
trips and working closely with country partners.
PMID- 23154378
TI - Optimizing the timing and technique of Treacher Collins orbital malar
reconstruction.
AB - The optimal timing and treatment of Treacher Collins syndrome with regard to
zygomatico-orbital osseous reconstruction has not been fully established. Osseous
reconstruction performed at an early age may result in bone graft resorption;
however, delays in surgical improvement may result in adverse psychosocial
effects on the patient. To study the optimal age for reconstruction clinically,
we examined 3 age groups based on timing of malar and eyelid reconstruction using
a three-dimensional computed tomographic scan and three-dimensional photometric
volume assessment. In addition, we collected outcome assessments from
parents/patients using satisfaction surveys. Of 73 patients with Treacher Collins
at the University of California Los Angeles Craniofacial Clinic, 45 had malar
reconstruction, complete records, and were available for study. The patients were
separated into 3 groups: (1) very young = 0 to 5 years, (2) mid-childhood = 6 to
12 years, and (3) adolescent/adult 13 years and older. As hypothesized, the 0 to
5 age group experienced the greatest percentage of complete bony resorption (77%)
compared with the 6 to 12 age group (only 4%) and the 13 and older age group
(0%). Interestingly, the 0 to 5 age group experienced the highest parent/patient
satisfaction, possibly owing to better psychosocial experience. When dealing with
treatment plans for patients with Treacher Collins, patients, parents, and
physicians must balance the benefits of early surgical intervention, such as
improved psychologic well-being, with the disadvantages of having to undergo a
greater number of procedures, such as fat grafting after malar bone graft
resorption.
PMID- 23154379
TI - Orthognathic surgery for obstructive sleep apnea: applying the principles to new
horizons in craniofacial surgery.
AB - This article is dedicated to the senior author Dr. Henry K. Kawamoto, Jr, who
pioneered the use of orthognathic surgery to treat severe obstructive sleep apnea
in 1981. Since that time, his techniques for maxillomandibular advancement have
been revised and expanded for improved surgical success. Obstructive sleep apnea
is a growing public health concern because it can cause hypertension, cardiac
arrhythmias, heart attack, stroke, and, in rare circumstances, sudden death if
untreated. When less invasive options fail such as weight loss or dental devices
for mandibular repositioning, maxillomandibular advancement is a valuable
treatment option for severe obstructive sleep apnea.
PMID- 23154382
TI - Experiences of early users of direct-to-consumer genomics in Switzerland: an
exploratory study.
AB - AIMS: This study explores attitudes, motivations and self-reported impact in
connection with direct-to-consumer (DTC) genomic testing amongst a group of life
scientists in Switzerland. METHODS: Data were collected through: (1) a self
completion online questionnaire, and (2) semi-structured qualitative interviews.
Forty participants completed the questionnaire and 10 were interviewed. RESULTS:
Curiosity was mentioned as the primary reason for undergoing testing, while less
significance was attributed to receiving actionable health information. The
opportunity to contribute to research ranked high as a motive for testing.
Overall, participants assessed their experience with the test as positive and
were willing to recommend it to others. Some reported that the testing had an
impact on how they view their health, but only a third of participants planned on
showing the results to health practitioners. Participants consistently referred
to 'fun' when describing several aspects of the testing experience. The 'fun
factor' manifested itself in different phases of the process, including the
motivation for taking the test, receiving the information and putting the test
results to use (including sharing and discussing it with others). This finding
suggests the need to further explore the concept of personal utility in DTC
genomics. CONCLUSIONS: Although this group is not representative of the broader
population due to both their scientific expertise and their willingness to try
out a controversial new technology, their experiences provide valuable insights
into the role of personal curiosity and altruism (fostering medical research) as
motivations for testing and the utility attributed to both.
PMID- 23154380
TI - It does not look odd to me: perceptual impairments and eye movements in amnesic
patients with medial temporal lobe damage.
AB - Studies of people with memory impairments have shown that a specific set of brain
structures in the medial temporal lobe (MTL) is vital for memory function.
However, whether these structures have a role outside of memory remains
contentious. Recent studies of amnesic patients with damage to two structures
within the MTL, the hippocampus and the perirhinal cortex, indicated that these
patients also performed poorly on perceptual tasks. More specifically, they
performed worse than controls when discriminating between objects, faces and
scenes with overlapping features. In order to investigate whether these
perceptual deficits are reflected in their viewing strategies, we tested a group
of amnesic patients with MTL damage that included the hippocampus and perirhinal
cortex on a series of oddity discrimination tasks in which they had to select an
odd item from a visual array. Participants' eye movements were monitored
throughout the experiment. Results revealed that patients were impaired on tasks
that required them to discriminate between items that shared many features, and
tasks that required processing items from different viewpoints. An analysis of
their eye movements revealed that they exhibited a similar viewing pattern as
controls: they fixated more on the target item on trials answered correctly, but
not on trials answered incorrectly. In addition, their impaired performance was
not explained by an abnormal viewing-strategy that assessed their use of working
memory. These results suggest that the perceptual deficits in the MTL patients
are not a consequence of abnormal viewing patterns of the objects and scenes, but
instead, could involve an inability to bind information gathered from several
fixations into a cohesive percept. These data also support the view that MTL
structures are important not only for long-term memory, but are also involved in
perceptual tasks.
PMID- 23154383
TI - Cocktail blood biomarkers: prediction of clinical outcomes in patients with acute
ischemic stroke.
AB - BACKGROUND: Timely prediction of stroke outcomes is important for proper
personalized treatment. In the present study, we aimed to develop cocktail blood
biomarkers to increase prediction efficiency using a combination of hemostasis,
inflammatory and repair-related biomarkers. METHODS: 105 patients suffering from
acute ischemic stroke were divided into good outcome group and poor outcome group
by modified Rankin Scale (mRS). Cytokines including CD40L, IFN-gamma, IL-1alpha,
IL-1beta, IL-6, IL-8, IL-17 and TNF-alpha, as well as hemostasis markers
fibrinogen, fibrin degradation products (FDP), D-dimer, tissue plasminogen
activator, and plasminogen activation inhibitor-1 in plasma were examined by
ELISA. Repair-related biomarker microRNA-210 (miR-210) was measured by real-time
PCR. The prediction efficiency was explored by receiver operator characteristic
analysis. RESULTS: We demonstrated that FDP, IL-6 and miR-210 levels were closely
associated with mRS in stroke patients. The prediction sensitivity of FDP, IL-6
and miR-210 for stroke outcome was 72.0, 86.7 and 82.5%, respectively. Using a
combination of biomarkers including FDP, IL-6 and miR-210, the prognostic
sensitivity of ischemic stroke increased to 95.2%. CONCLUSION: The combination of
FDP, IL-6 and miR-210 has a high sensitivity for predicting stroke recovery, it
serves as a potential cocktail blood biomarker. It provides a novel approach for
stroke prognosis.
PMID- 23154384
TI - Effect of embryo density on in vitro development and gene expression in bovine in
vitro-fertilized embryos cultured in a microwell system.
AB - To identify embryos individually during in vitro development, we previously
developed the well-of-the-well (WOW) dish, which contains 25 microwells. Here we
investigated the effect of embryo density (the number of embryos per volume of
medium) on in vitro development and gene expression of bovine in vitro-fertilized
embryos cultured in WOW dishes. Using both conventional droplet and WOW culture
formats, 5, 15, and 25 bovine embryos were cultured in 125 MUl medium for 168 h.
The blastocysts at Day 7 were analyzed for number of cells and expression of ten
genes (CDX2, IFN-tau, PLAC8, NANOG, OCT4, SOX2, AKR1B1, ATP5A1, GLUT1 and IGF2R).
In droplet culture, the rates of formation of >4-cell cleavage embryos and
blastocysts were significantly lower in embryos cultured at 5 embryos per droplet
than in those cultured at 15 or 25 embryos per droplet, but not in WOW culture.
In both droplet and WOW culture, developmental kinetics and blastocyst cell
numbers did not differ among any groups. IFN-tau expression in embryos cultured
at 25 embryos per droplet was significantly higher than in those cultured at 15
embryos per droplet and in artificial insemination (AI)-derived blastocysts.
Moreover, IGF2R expression was significantly lower in the 25-embryo group than in
the 5-embryo group and in AI-derived blastocysts. In WOW culture, these
expressions were not affected by embryo density and were similar to those in AI
derived blastocysts. These results suggest that, as compared with conventional
droplet culture, in vitro development and expression of IFN-tau and IGF2R in the
microwell system may be insensitive to embryo density.
PMID- 23154385
TI - Ascorbic acid improves the developmental competence of porcine oocytes after
parthenogenetic activation and somatic cell nuclear transplantation.
AB - In this study, a dose-response assessment was performed to understand the
relation between supplementation of media with L-ascorbic acid or vitamin C and
porcine oocyte maturation and the in vitro development of parthenotes (PA) and
handmade cloned (HMC) embryos. Various concentrations (0, 25, 50 and 100 MUg/ml)
of vitamin C supplemented in in vitro maturation (IVM) and culture (IVC) media
were tested. None of these vitamin C additions affected nuclear maturation of
oocytes, yet supplementation at 50 MUg/ml led to significantly increased
intracellular glutathione (GSH) levels and reduced reactive oxygen species (ROS).
When cultured in IVM- and/or IVC-supplemented media, the group supplemented with
50 MUg/ml of vitamin C showed improved cleavage rates, blastocyst rates and total
cell numbers per blastocyst (P<0.05) compared with other groups (control, 25
MUg/ml and 100 MUg/ml). In contrast, supplementation with 50 MUg/ml vitamin C
decreased (P<0.05) the apoptosis index as compared with the groups supplemented
with 100 MUg/ml. In addition, even with a lower blastocyst rate to start with
(37.6 vs. 50.3%, P<0.05), supplementation of HMC embryos with vitamin C
ameliorated their blastocyst quality to the extent of PA embryos as indicated by
their total cell numbers (61.2 vs. 59.1). Taken together, an optimized
concentration of vitamin C supplementation in the medium not only improves
blastocyst rates and total cell numbers but also reduces apoptotic indices,
whereas overdosages compromise various aspects of the development of parthenotes
and cloned porcine embryos.
PMID- 23154386
TI - Capillary electrophoresis with three-color fluorescence detection for the
analysis of glycosphingolipid metabolism.
AB - A capillary electrophoresis system with an ultrasensitive three-color laser
induced fluorescence detector was constructed for the simultaneous measurement of
glycosphingolipids conjugated with a family of BODIPY fluorophores. The compounds
were separated by capillary electrophoresis and detected by laser-induced
fluorescence excited within a sheath-flow cuvette. Diode-pumped solid-state
lasers operating at 473 nm and 532 nm, and a diode laser operating at 633 nm were
used to excite glycosphingolipids tagged with BODIPY-FL, BODIPY-TMR, and BODIPY
650/665 fluorophores. Detection limits were 34 +/- 1 molecules, 67 +/- 7
molecules, and 36 +/- 13 molecules of BODIPY-FL, BODIPY-TMR, and BODIPY-650/665
labeled glycosphingolipids. Separation efficiencies were typically one million
theoretical plates. To test the ability of the system to analyze cellular
contents in an in vitro biological model, differentiated PC12 cells were co
incubated with BODIPY-FL, BODIPY-TMR, and BODIPY-650/665 labeled lactosylceramide
substrates. Cells were homogenized. The metabolic products originating from the
glycosphingolipid substrates were simultaneously analyzed using the system.
PMID- 23154388
TI - Recruitment of Grb2 and SHIP1 by the ITT-like motif of TIGIT suppresses granule
polarization and cytotoxicity of NK cells.
AB - Activating and inhibitory receptors control natural killer (NK) cell activity. T
cell immunoglobulin and ITIM (immunoreceptor tyrosine-based inhibition motif)
domain (TIGIT) was recently identified as a new inhibitory receptor on T and NK
cells that suppressed their effector functions. TIGIT harbors the immunoreceptor
tail tyrosine (ITT)-like and ITIM motifs in its cytoplasmic tail. However, how
its ITT-like motif functions in TIGIT-mediated negative signaling is still
unclear. Here, we show that TIGIT/PVR (poliovirus receptor) engagement disrupts
granule polarization leading to loss of killing activity of NK cells. The ITT
like motif of TIGIT has a major role in its negative signaling. After TIGIT/PVR
ligation, the ITT-like motif is phosphorylated at Tyr225 and binds to cytosolic
adapter Grb2, which can recruit SHIP1 to prematurely terminate
phosphatidylinositol 3-kinase (PI3K) and MAPK signaling, leading to
downregulation of NK cell function. In support of this, Tyr225 or Asn227 mutation
leads to restoration of TIGIT/PVR-mediated cytotoxicity, and SHIP1 silencing can
dramatically abolish TIGIT/PVR-mediated killing inhibition.
PMID- 23154387
TI - The Ca2+/Mn2+ ion-pump PMR1 links elevation of cytosolic Ca(2+) levels to alpha
synuclein toxicity in Parkinson's disease models.
AB - Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic
neurons, which arises from a yet elusive concurrence between genetic and
environmental factors. The protein alpha-synuclein (alphaSyn), the principle
toxic effector in PD, has been shown to interfere with neuronal Ca(2+) fluxes,
arguing for an involvement of deregulated Ca(2+) homeostasis in this neuronal
demise. Here, we identify the Golgi-resident Ca(2+)/Mn(2+) ATPase PMR1 (plasma
membrane-related Ca(2+)-ATPase 1) as a phylogenetically conserved mediator of
alphaSyn-driven changes in Ca(2+) homeostasis and cytotoxicity. Expression of
alphaSyn in yeast resulted in elevated cytosolic Ca(2+) levels and increased cell
death, both of which could be inhibited by deletion of PMR1. Accordingly, absence
of PMR1 prevented alphaSyn-induced loss of dopaminergic neurons in nematodes and
flies. In addition, alphaSyn failed to compromise locomotion and survival of
flies when PMR1 was absent. In conclusion, the alphaSyn-driven rise of cytosolic
Ca(2+) levels is pivotal for its cytotoxicity and requires PMR1.
PMID- 23154389
TI - Regulation of endodermal differentiation of human embryonic stem cells through
integrin-ECM interactions.
AB - Many cellular responses during development are regulated by interactions between
integrin receptors and extracellular matrix proteins (ECMPs). Although the
majority of recent studies in human embryonic stem cell (hESC) differentiation
have focused on the role of growth factors, such as FGF, TGFbeta, and WNT,
relatively little is known about the role of ECMP-integrin signaling in this
process. Moreover, current strategies to direct hESC differentiation into various
lineages are inefficient and have yet to produce functionally mature cells in
vitro. This suggests that additional factors, such as ECMPs, are required for the
efficient differentiation of hESCs. Using a high-throughput multifactorial
cellular array technology, we investigated the effect of hundreds of ECMP
combinations and concentrations on differentiation of several hPSC lines to
definitive endoderm (DE), an early embryonic cell population fated to give rise
to internal organs such as the lung, liver, pancreas, stomach, and intestine.
From this screen we identified fibronectin (FN) and vitronectin (VTN) as ECMP
components that promoted DE differentiation. Analysis of integrin expression
revealed that differentiation toward DE led to an increase in FN-binding integrin
alpha5 (ITGA5) and VTN-binding integrin alphaV (ITGAV). Conditional short hairpin
RNA-mediated knockdown of ITGA5 and ITGAV disrupted hESC differentiation toward
DE. Finally, fluorescence-based cell sorting for ITGA5 and ITGAV significantly
enriched cells with gene expression signatures associated with DE, demonstrating
that these cell surface proteins permit isolation and enrichment of DE from
hESCs. These data provide evidence that FN and VTN promote endoderm
differentiation of hESCs through interaction with ITGA5 and ITGAV, and that ECMP
integrin interactions are required for hESC differentiation into functionally
mature cells.
PMID- 23154390
TI - Surface chemistry-mediated penetration and gold nanorod thermotherapy in
multicellular tumor spheroids.
AB - We investigated the penetration and thermotherapy efficiency of different surface
coated gold nanorods (Au NRs) in multicellular tumor spheroids. The current data
show that negatively charged Au NRs, other than positively charged Au NRs, can
penetrate deep into the tumor spheroids and achieve a significant thermal
therapeutic benefit.
PMID- 23154391
TI - A double-blinded randomized controlled trial of laparoendoscopic single-site
access versus conventional 3-port appendectomy.
AB - OBJECTIVE: The aim of the current study was to perform a multicentered
prospective double-blinded randomized controlled trial comparing laparoendoscopic
single-site access (LESS) versus conventional three-port laparoscopic
appendectomy (TPLA). BACKGROUND: The clinical benefits and disadvantages of LESS
appendectomy are uncertain. METHODS: Between October 2009 and March 2011,
consecutive patients admitted with clinical or radiological evidence of
appendicitis were randomly assigned to receive either LESS or TPLA. The main
outcome measurement was overall pain score. Secondary outcome measurements
included operative time, conversion rates, morbidity rates, activity pain scores,
activity scores, patient satisfaction, and cosmesis scores. RESULTS: During the
study period, 200 patients were recruited to the study. There were no significant
differences in the morbidity rates, operative time, conversion rates, and
postoperative recovery. There were also no differences in the overall pain score
and pain score at rest. However, patients in the LESS group experienced
significantly more pain upon coughing or standing and required more intravenous
analgesics (P = 0.001, 0.038, and 0.035, respectively). Wound cosmesis and
satisfaction scores on the contrary were better in the LESS group (P = 0.002 and
P = 0.052). No differences in the quality-of-life assessments were present at 2
weeks after operation. CONCLUSIONS: LESS and conventional appendectomy resulted
in similar perioperative outcomes. However, LESS appendectomy resulted in worst
pain scores upon exertion and required a higher dosage of intravenous analgesics
when compared with TPLA. On the contrary, wound cosmesis and satisfaction scores
were better in the LESS group. Hence, adoption of the technique for appendectomy
will depend on patient preferences and the presence of local expertise.
PMID- 23154392
TI - Long-term outcomes of the australasian randomized clinical trial comparing
laparoscopic and conventional open surgical treatments for colon cancer: the
Australasian Laparoscopic Colon Cancer Study trial.
AB - OBJECTIVE: : We report a multicentered randomized controlled trial across
Australia and New Zealand comparing laparoscopic-assisted colon resection (LCR)
with open colon resection (OCR) for colon cancer. BACKGROUND: : Colon cancer is a
significant worldwide health issue. This trial investigated whether the short
term benefits associated with LCR for colon cancer could be achieved safely,
without survival disadvantages, in our region. METHODS: : A total of 601 patients
with potentially curable colon cancer were randomized to receive LCR or OCR.
Primary endpoints were 5-year overall survival, recurrence-free survival, and
freedom from recurrence rates, compared using an intention-to-treat analysis.
RESULTS: : On April 5, 2010, 587 eligible patients were followed for a median of
5.2 years (range, 1 week-11.4 years) with 5-year confirmed follow-up data for
survival and recurrence on 567 (96.6%). Significant differences between the 2
trial groups were as follows: LCR patients were older at randomization, and their
pathology specimens showed smaller distal resection margins; OCR patients had
some worse pathology parameters, but there were no differences in disease stages.
There were no significant differences between the LCR and OCR groups in 5-year
follow-up of overall survival (77.7% vs 76.0%, P = 0.64), recurrence-free
survival (72.7% vs 71.2%, P = 0.70), or freedom from recurrence (86.2% vs 85.6%,
P = 0.85). CONCLUSIONS: : In spite of some differences in short-term surrogate
oncological markers, LCR was not inferior to OCR in direct measures of survival
and disease recurrence. These findings emphasize the importance of long-term data
in formulating evidence-based practice guidelines.
PMID- 23154393
TI - Axillary dissection versus no axillary dissection in older patients with T1N0
breast cancer: 15-year results of a randomized controlled trial.
AB - OBJECTIVE: To assess the role of axillary dissection in older breast cancer
patients with a clinically clear axilla. BACKGROUND: Axillary dissection, once
standard treatment for breast cancer, is associated with considerable morbidity.
It has been substituted by sentinel node biopsy with dissection only if the
sentinel node is positive. We aimed to determine whether axillary surgery can be
omitted in older women, thereby sparing them morbidity, without compromising long
term disease control. METHODS: We carried out a randomized clinical trial on 238
older (65-80 years) breast cancer patients, with clinically N0 disease of
radiographic diameter 2 cm or less. Patients were randomized to quadrantectomy
with or without axillary dissection. All received radiotherapy to the residual
breast but not the axilla; all were prescribed tamoxifen for 5 years. Main
outcome measures were overall survival and breast cancer mortality. We also
assessed overt axillary disease in those who did not receive axillary dissection.
RESULTS: After 15 years of follow-up, distant metastasis rate, overall survival,
and breast cancer mortality in the axillary dissection and no axillary dissection
arms were indistinguishable. The 15-year cumulative incidence of overt axillary
disease in the no axillary dissection arm was only 6%. CONCLUSIONS: Older
patients with early breast cancer and a clinically clear axilla treated by
conservative surgery, postoperative radiotherapy, and adjuvant tamoxifen do not
benefit from axillary dissection. This study was registered at clinicaltrials.gov
(ID NCT00002720).
PMID- 23154394
TI - Nonoperative management of rectal cancer with complete clinical response after
neoadjuvant therapy.
AB - INTRODUCTION: Nonoperative management (NOM) of rectal cancer after a complete
clinical response (cCR) to neoadjuvant therapy is controversial. In this article,
we retrospectively reviewed the outcomes of patients managed with selective NOM
after a cCR to neoadjuvant treatment and compared these with patients who
underwent standard rectal resection with a pathological complete response (pCR).
METHODS: Patients completing neoadjuvant chemoradiotherapy (CRT) for stage I to
III rectal cancer between January 2006 and August 2010 were retrospectively
reviewed. Median follow-up was calculated in months after completion of CRT.
RESULTS: Thirty-two patients (median follow-up 28 months) were treated by NOM
after a cCR. Among 265 treated by CRT and rectal resection, 57 patients (22%) had
a pCR and formed the control group (median follow-up 43 months). Factors
associated with selective use of NOM included lower pretreatment stage, older
age, and distal tumor location (P < 0.05). In the NOM group, 6 recurred locally
(median 11 months, range 7-14), 3 of whom also had concurrent distant recurrence.
All 6 local failures were controlled by salvage rectal resection with no further
local recurrence of disease (median follow-up 17 months). In the rectal
resection/pCR group, there were no local failures. The 2-year distant disease
free survival (88% vs 98%, P = 0.27) and overall survival (96% vs 100%, P = 0.56)
were similar for NOM and rectal resection/pCR groups. CONCLUSIONS: Rectal
resection was successfully avoided in 81% of patients selected for NOM. When
combined with salvage surgery, NOM appears to achieve similar local and distant
disease control compared with patients with a pCR treated by rectal resection.
Longer follow-up and prospective trials are warranted to evaluate this promising
treatment option.
PMID- 23154395
TI - Changes of quality of life in gastric cancer patients after curative resection: a
longitudinal cohort study in Korea.
AB - OBJECTIVE: Little is known about how quality of life (QOL) changes over time
after gastrectomy. We prospectively examined changes of QOL in Korean patients
with gastric cancer after curative resection. BACKGROUND: As early detection and
improved treatment have led to higher survival rates and an increasing number of
long-term survivors, the importance of QOL has increased. METHODS: Patients newly
diagnosed with gastric cancer, who were expected to undergo curative resection,
were studied. QOL was assessed, using the European Organization for Research and
Treatment of Cancer QLQ-C30 and its gastric module QLQ-STO22, before and after 3
and 12 months of gastrectomy. RESULTS: In total, 465 patients were included in
the study, and 377 and 88 patients underwent subtotal gastrectomy and total
gastrectomy, respectively. For most of the functional or symptom scales, the mean
score deteriorated at 3 months and generally improved during follow-up period.
Patients with total gastrectomy had more functional and symptomatic problems
related to QOL than those with subtotal gastrectomy during the follow-up. For
both groups, there were temporal, unrecovered, improved, and unchanged problems
in QOL. Fatigue; digestive symptoms such as diarrhea, dysphagia, and eating
restrictions; body image disturbance; and cognitive functioning were the
representative unrecovered problems, which persisted at 12 months after surgery.
CONCLUSIONS: Our findings show that there are various functional and symptomatic
problems, which health care providers need to manage during the postsurgical
period. We need to continuously address fatigue, diarrhea, dysphagia, eating
restrictions, body image disturbance, and cognitive functioning. In addition, it
would be necessary to inform patients about possible QOL outcomes while they are
receiving information about surgery and signing informed consent for surgery.
PMID- 23154396
TI - Appendicectomy is associated with increased pregnancy rate: a cohort study.
AB - OBJECTIVE: This study was carried out to determine whether pregnancy rate is
reduced after appendicitis or appendicectomy. BACKGROUND: The association between
appendicectomy, appendicitis, and subsequent fertility is controversial. METHODS:
A cohort study was carried out in the Medicines Monitoring database. The cohort
of women who underwent appendicectomy and appropriate comparators were followed
up until first pregnancy after appendicectomy date. Pathology of the appendix was
verified manually. The association between appendicectomy, appendicitis, and
pregnancy was determined by Cox regression models. RESULTS: The age and social
deprivation score-matched analyses included 2935 patients who had appendicectomy
with 5870 comparators. There were 1277 (43.5%) pregnancies in the appendicectomy
cohort and 2319 (39.5%) in the comparator cohort during a mean follow-up of 12.4
(standard deviation: 7.3) years. The adjusted hazard ratios (HRs) for pregnancy
rates were 1.20 (95% confidence interval [CI]: 1.10-1.31). In an unmatched cohort
analysis (3009 in the appendicectomy cohort and 122,912 in the comparator
cohort), the adjusted HRs for pregnancy rates were 1.65 (95% CI: 1.55-1.75).
Within the histologically proven appendicitis subset, the adjusted HR was 1.21
(95% CI: 1.08-1.37) in comparison with the matched comparator cohort. In
comparison with the group of participants who had appendicectomy for a normal
appendix, the HRs were 0.98 (95% CI: 0.83-1.15) for mucosal and catarrhal
appendicitis, 0.72 (95% CI: 0.64-0.82) for suppurative appendicitis, and 0.64
(95% CI: 0.50-0.80) for gangrenous appendicitis. CONCLUSIONS: Appendicectomy and
early appendicitis were associated with increased pregnancy rates. Young women
with early appendicitis had better pregnancy rates than those with advanced
appendicitis. Early referral for laparoscopy and appendicectomy is advocated.
PMID- 23154397
TI - Association between cholecystectomy and intestinal cancer: a national record
linkage study.
AB - OBJECTIVE: To investigate the risk of intestinal cancer in a cohort of people who
had undergone cholecystectomy for gallstones, and in a cohort of people who had
been hospitalized for gallbladder disease but had not undergone cholecystectomy.
BACKGROUND: Some investigators have suggested that cholecystectomy increases the
risk of intestinal cancer. Despite extensive study, the evidence remains
inconclusive. If there is doubt about safety, the question arises of whether
patients considering the operation should be told of a possible risk. It is also
increasingly clear that there are noncausal associations between gallstones and
intestinal cancer. METHOD: Analysis of record-linked hospital admission and
mortality statistics for England from 1998 to 2008; calculation of ratio of rates
of cancers in the cholecystectomy cohort and the gallbladder disease cohort
compared with a control cohort. RESULTS: : In the first year after
cholecystectomy, the rate ratios for cancer of the small intestine, colon, and
rectum were significantly high at, respectively, 4.6 (95% confidence interval 3.9
5.5), 2.0 (1.9-2.1), and 1.7 (1.6-1.9). Rates of these cancers were also
significantly high in people with gallstones without cholecystectomy. By 8 to 10
years after cholecystectomy, rate ratios had declined to nonsignificant levels.
CONCLUSIONS: These cancers are associated with gallstones. The highest elevation
of risk of cancer after cholecystectomy was at the shortest time interval after
operation. Thereafter, the level of risk in the cholecystectomy and control
cohorts gradually converged. The association in this study, between
cholecystectomy and intestinal cancer, is very unlikely to be causal. Intestinal
cancers are, on occasion, initially misdiagnosed as gallbladder disease.
PMID- 23154399
TI - Discussion of the applicability of positive lymph node ratio as a proper N
staging for predication the prognosis of gastric cancer after curative surgery
plus extended lymphadenectomy.
PMID- 23154401
TI - Laminin-211 in skeletal muscle function.
AB - A chain is no stronger than its weakest link is an old idiom that holds true for
muscle biology. As the name implies, skeletal muscle's main function is to move
the bones. However, for a muscle to transmit force and withstand the stress that
contractions give rise to, it relies on a chain of proteins attaching the
cytoskeleton of the muscle fiber to the surrounding extracellular matrix. The
importance of this attachment is illustrated by a large number of muscular
dystrophies caused by interruption of the cytoskeletal-extracellular matrix
interaction. One of the major components of the extracellular matrix is laminin,
a heterotrimeric glycoprotein and a major constituent of the basement membrane.
It has become increasingly apparent that laminins are involved in a multitude of
biological functions, including cell adhesion, differentiation, proliferation,
migration and survival. This review will focus on the importance of laminin-211
for normal skeletal muscle function.
PMID- 23154402
TI - Ste20-like kinase SLK, at the crossroads: a matter of life and death.
AB - Reorganization of the cytoskeleton is necessary for apoptosis, proliferation,
migration, development and tissue repair. However, it is well established that
mutations or overexpression of key regulators contribute to the phenotype and
progression of several pathologies such as cancer. For instance, c-src mutations
and the overexpression of FAK have been implicated in the invasive and metastatic
process, suggesting that components of the motility system may represent a new
class of therapeutic targets. Over the last several years, we and others have
established distinct roles for the Ste20-like kinase SLK, encompassing apoptosis,
growth, motility and development. Here, we review the SLK field from its initial
cloning to the most recent findings from our laboratory. We summarize the various
roles of SLK and the biochemical mechanisms that regulate its activity. These
various findings reveal very complex functions and pattern of regulation for SLK
in development and cancer, making it a potential therapeutic target.
PMID- 23154403
TI - Laminins and retinal vascular development.
AB - The mechanisms controlling vascular development, both normal and pathological,
are not yet fully understood. Many diseases, including cancer and diabetic
retinopathy, involve abnormal blood vessel formation. Therefore, increasing
knowledge of these mechanisms may help develop novel therapeutic targets. The
identification of novel proteins or cells involved in this process would be
particularly useful. The retina is an ideal model for studying vascular
development because it is easy to access, particularly in rodents where this
process occurs post-natally. Recent studies have suggested potential roles for
laminin chains in vascular development of the retina. This review will provide an
overview of these studies, demonstrating the importance of further research into
the involvement of laminins in retinal blood vessel formation.
PMID- 23154405
TI - Electrical and structural properties of antimony-doped p-type ZnO nanorods with
self-corrugated surfaces.
AB - We report on p-type conductivity in antimony (Sb)-doped ZnO (ZnO:Sb) nanorods
which have self-corrugated surfaces. The p-ZnO:Sb/n-ZnO nanorod diode shows good
rectification characteristics, confirming that a p-n homojunction is formed in
the ZnO nanorod diode. The low-temperature photoluminescence (PL) spectra of the
ZnO:Sb nanorods reveal that the p-type conductivity in p-ZnO:Sb is related to the
Sb(Zn)-2V(Zn) complex acceptors. Transmission electron microscopy (TEM) analysis
of the ZnO:Sb nanorods also shows that the p-type conductivity is attributed to
the Sb(Zn)-2V(Zn) complex acceptors which can be easily formed near the self
corrugated surface regions of ZnO:Sb nanorods. These results suggest that the
Sb(Zn)-2V(Zn) complex acceptors are mainly responsible for the p-type
conductivity in ZnO:Sb nanorods which have corrugated surfaces.
PMID- 23154404
TI - Protein composition and biomechanical properties of in vivo-derived basement
membranes.
AB - Basement membranes (BMs) evolved together with the first metazoan species
approximately 500 million years ago. Main functions of BMs are stabilizing
epithelial cell layers and connecting different types of tissues to functional,
multicellular organisms. Mutations of BM proteins from worms to humans are either
embryonic lethal or result in severe diseases, including muscular dystrophy,
blindness, deafness, kidney defects, cardio-vascular abnormalities or retinal and
cortical malformations. In vivo-derived BMs are difficult to come by; they are
very thin and sticky and, therefore, difficult to handle and probe. In addition,
BMs are difficult to solubilize complicating their biochemical analysis. For
these reasons, most of our knowledge of BM biology is based on studies of the BM
like extracellular matrix (ECM) of mouse yolk sac tumors or from studies of the
lens capsule, an unusually thick BM. Recently, isolation procedures for a variety
of BMs have been described, and new techniques have been developed to directly
analyze the protein compositions, the biomechanical properties and the biological
functions of BMs. New findings show that native BMs consist of approximately 20
proteins. BMs are four times thicker than previously recorded, and proteoglycans
are mainly responsible to determine the thickness of BMs by binding large
quantities of water to the matrix. The mechanical stiffness of BMs is similar to
that of articular cartilage. In mice with mutation of BM proteins, the stiffness
of BMs is often reduced. As a consequence, these BMs rupture due to mechanical
instability explaining many of the pathological phenotypes. Finally, the
morphology and protein composition of human BMs changes with age, thus BMs are
dynamic in their structure, composition and biomechanical properties.
PMID- 23154406
TI - Angiopoietin-like protein 2 sensitively responds to weight reduction induced by
lifestyle intervention on overweight Japanese men.
AB - OBJECTIVE: Overexpression of Angiopoietin-like protein 2 (Angptl2) in obese
adipose tissues promotes adipose tissue inflammation and its-related metabolic
abnormalities. In a comparative study with adiponectin, we investigated whether
alterations in serum Angptl2 concentrations reflect the effect of lifestyle
intervention on weight loss and improved metabolic parameters in overweight
subjects. METHODS: A total of 154 Japanese men (age, 40.9+/-5.1 years; body mass
index, 26.9+/-3.6 kg m(-2); abdominal circumference, 94.1+/-8.9 cm) underwent a 3
month lifestyle intervention and underwent follow-up for 3 months thereafter.
RESULTS: Decreased serum Angptl2 levels, but not increased serum adiponectin
levels, were immediately apparent at the end of 3-month lifestyle intervention.
Angptl2 levels continued to decrease for 3 months in parallel with body weight
loss and improvement in metabolic indicators. In subjects showing ?6% weight
reduction, markedly reduced Angptl2 levels were detected at the end of 3-month
intervention, whereas increased adiponectin levels were detected 3 months after
the end of intervention. Multivariate analysis revealed changes in serum Angptl2
levels associated with changes in triglycerides (TGs), aspartate aminotransferase
and alanine aminotransferase. In contrast, changes in serum adiponectin levels
were associated with altered high-density lipoprotein cholesterol (HDL-C) and
fasting plasma glucose levels. CONCLUSION: A 3-month lifestyle intervention
promoted weight reduction and improved glucose and lipid metabolism, an effect
maintained 3 months later. Notably, our findings indicate that decreased Angptl2
levels are a good indicator of reduced visceral fat and metabolic improvement at
early stages of lifestyle intervention. Thus, Angptl2 reflects adiposity and
might be a key protein to regulate inflammation and TG metabolism, whereas
adiponectin levels could reflect improved glucose and HDL-C metabolism.
PMID- 23154407
TI - Vitamin D status and parathyroid hormone levels in patients with obstructive
sleep apnea.
AB - BACKGROUND: Vitamin D insufficiency and high levels of parathyroid hormone (PTH)
appear to be emerging risk factors for metabolic syndrome (MS), diabetes and
cardiovascular disease, conditions that occur frequently in patients with
obstructive sleep apnea syndrome (OSAS). OBJECTIVES: This study examined whether
serum concentrations of 25-hydroxyvitamin D [25(OH)D] and PTH were associated
with the presence of MS, diabetes and hypertension among an OSAS population.
METHODS: A total of 826 patients (635 men and 191 women) with newly diagnosed
OSAS were studied. The occurrence of the MS was analyzed according to the
National Cholesterol Education Program Adult Treatment Panel III clinical
criteria. Serum levels of 25(OH)D, PTH, glucose, triglycerides, cholesterol, HDL
cholesterol, creatinine and uric acid were determined. RESULTS: In 55.3% of the
men and in 63.2% of the women, the serum 25(OH)D level was less than 30 ng/ml
(insufficient status). After adjusting for age, sex and seasonality, there was a
significant trend of decreasing odds for diabetes [odds ratio (OR) 0.55, 95%
confidence interval (CI) 0.33-0.94, ptrend = 0.038] and MS (OR 0.34, 95% CI 0.21
0.56, ptrend < 0.001) with increasing vitamin D levels. Higher PTH levels were
associated with a higher prevalence of obesity (OR 2.05, 95% CI 1.06-3.09, ptrend
< 0.001) and hypertension (OR 1.83, 95% CI 1.01-3.05, ptrend = 0.049).
CONCLUSIONS: These data suggest an inverse association of 25(OH)D with diabetes
and MS and a positive association of PTH with obesity and hypertension among
patients with OSAS. Based on our observational study, the causative nature of the
associations cannot be established. These findings require further examination in
prospective studies including clinical trials.
PMID- 23154408
TI - Spinal fracture in a dog with diffuse idiopathic skeletal hyperostosis.
AB - A six-year-old, spayed female Weimaraner dog was first presented with the
complaint of hindlimb paresis and then hindlimb paralysis two years later after
colliding with a tree. Radiographs and computed tomography revealed spinal
fractures at lumbar vertebrae (L)2-3 and at L4-5. In addition, the spinal column
was affected by new bone formation along the vertebral bodies, bridging the disc
spaces, as seen in diffuse idiopathic skeletal hyperostosis (DISH). Open
reduction and internal fixation was achieved with standard vertebral body
plating. This is the first report of DISH-associated spinal fractures after minor
trauma in a dog. Surgery resulted in return of the full function after the first,
and in improvement of neurologic function after the second incident.
PMID- 23154409
TI - Tif1gamma is essential for the terminal differentiation of mammary alveolar
epithelial cells and for lactation through SMAD4 inhibition.
AB - Transforming growth factor beta (TGFbeta) is widely recognised as an important
factor that regulates many steps of normal mammary gland (MG) development,
including branching morphogenesis, functional differentiation and involution.
Tif1gamma has previously been reported to temporally and spatially control
TGFbeta signalling during early vertebrate development by exerting negative
effects over SMAD4 availability. To evaluate the contribution of Tif1 gamma to MG
development, we developed a Cre/LoxP system to specifically invalidate the Tif1g
gene in mammary epithelial cells in vivo. Tif1g-null mammary gland development
appeared to be normal and no defects were observed during the lifespan of virgin
mice. However, a lactation defect was observed in mammary glands of Tif1g-null
mice. We demonstrate that Tif1 gamma is essential for the terminal
differentiation of alveolar epithelial cells at the end of pregnancy and to
ensure lactation. Tif1 gamma appears to play a crucial role in the crosstalk
between TGFbeta and prolactin pathways by negatively regulating both PRL receptor
expression and STAT5 phosphorylation, thereby impairing the subsequent
transactivation of PRL target genes. Using HC11 cells as a model, we demonstrate
that the effects of Tif1g knockdown on lactation depend on both SMAD4 and
TGFbeta. Interestingly, we found that the Tif1gamma expression pattern in mammary
epithelial cells is almost symmetrically opposite to that described for TGFbeta.
We propose that Tif1gamma contributes to the repression of TGFbeta activity
during late pregnancy and prevents lactation by inhibiting SMAD4.
PMID- 23154410
TI - Distinct requirements for wnt9a and irf6 in extension and integration mechanisms
during zebrafish palate morphogenesis.
AB - Development of the palate in vertebrates involves cranial neural crest migration,
convergence of facial prominences and extension of the cartilaginous framework.
Dysregulation of palatogenesis results in orofacial clefts, which represent the
most common structural birth defects. Detailed analysis of zebrafish
palatogenesis revealed distinct mechanisms of palatal morphogenesis: extension,
proliferation and integration. We show that wnt9a is required for palatal
extension, wherein the chondrocytes form a proliferative front, undergo
morphological change and intercalate to form the ethmoid plate. Meanwhile, irf6
is required specifically for integration of facial prominences along a V-shaped
seam. This work presents a mechanistic analysis of palate morphogenesis in a
clinically relevant context.
PMID- 23154411
TI - The Drosophila WIF1 homolog Shifted maintains glypican-independent Hedgehog
signaling and interacts with the Hedgehog co-receptors Ihog and Boi.
AB - Hedgehog (Hh) family proteins are secreted signaling ligands whose short- and
long-range activities transform cellular fates in multiple contexts in organisms
ranging from metazoans to humans. In the developing Drosophila wing,
extracellular Hh binds to cell-bound glypican heparan sulfate proteoglycans
(HSPGs) and the secreted protein Shifted (Shf), a member of Wnt inhibitory factor
1 (WIF1) family. The glypicans and Shf are required for long-range Hh movement
and signaling; it has been proposed that Shf promotes long-range Hh signaling by
reinforcing binding between Hh and the glypicans, and that much or all of
glypican function in Hh signaling requires Shf. However, we will show here that
Shf maintains short-range Hh signaling in the wing via a mechanism that does not
require the presence of or binding to the Drosophila glypicans Dally and Dally
like protein. Conversely, we demonstrate interactions between Hh and the
glypicans that are maintained, and even strengthened, in the absence of Shf. We
present evidence that Shf binds to the CDO/BOC family Hh co-receptors
Interference hedgehog (Ihog) and Brother of Ihog, suggesting that Shf regulates
short-range Hh signaling through interactions with the receptor complex. In
support of a functional interaction between Ihog and members of the Shf/WIF1
family, we show that Ihog can increase the Wnt-inhibitory activity of vertebrate
WIF1; this result raises the possibility of interactions between WIF1 and
vertebrate CDO/BOC family members.
PMID- 23154412
TI - A Hh-driven gene network controls specification, pattern and size of the
Drosophila simple eyes.
AB - During development, extracellular signaling molecules interact with intracellular
gene networks to control the specification, pattern and size of organs. One such
signaling molecule is Hedgehog (Hh). Hh is known to act as a morphogen,
instructing different fates depending on the distance to its source. However, how
Hh, when signaling across a cell field, impacts organ-specific transcriptional
networks is still poorly understood. Here, we investigate this issue during the
development of the Drosophila ocellar complex. The development of this sensory
structure, which is composed of three simple eyes (or ocelli) located at the
vertices of a triangular patch of cuticle on the dorsal head, depends on Hh
signaling and on the definition of three domains: two areas of eya and so
expression--the prospective anterior and posterior ocelli--and the intervening
interocellar domain. Our results highlight the role of the homeodomain
transcription factor engrailed (en) both as a target and as a transcriptional
repressor of hh signaling in the prospective interocellar region. Furthermore, we
identify a requirement for the Notch pathway in the establishment of en
maintenance in a Hh-independent manner. Therefore, hh signals transiently during
the specification of the interocellar domain, with en being required here for hh
signaling attenuation. Computational analysis further suggests that this network
design confers robustness to signaling noise and constrains phenotypic variation.
In summary, using genetics and modeling we have expanded the ocellar gene network
to explain how the interaction between the Hh gradient and this gene network
results in the generation of stable mutually exclusive gene expression domains.
In addition, we discuss some general implications our model may have in some Hh
driven gene networks.
PMID- 23154413
TI - Genetic elevation of sphingosine 1-phosphate suppresses dystrophic muscle
phenotypes in Drosophila.
AB - Duchenne muscular dystrophy is a lethal genetic disease characterized by the loss
of muscle integrity and function over time. Using Drosophila, we show that
dystrophic muscle phenotypes can be significantly suppressed by a reduction of
wunen, a homolog of lipid phosphate phosphatase 3, which in higher animals can
dephosphorylate a range of phospholipids. Our suppression analyses include
assessing the localization of Projectin protein, a titin homolog, in sarcomeres
as well as muscle morphology and functional movement assays. We hypothesize that
wunen-based suppression is through the elevation of the bioactive lipid
Sphingosine 1-phosphate (S1P), which promotes cell proliferation and
differentiation in many tissues, including muscle. We confirm the role of S1P in
suppression by genetically altering S1P levels via reduction of S1P lyase (Sply)
and by upregulating the serine palmitoyl-CoA transferase catalytic subunit gene
lace, the first gene in the de novo sphingolipid biosynthetic pathway and find
that these manipulations also reduce muscle degeneration. Furthermore, we show
that reduction of spinster (which encodes a major facilitator family transporter,
homologs of which in higher animals have been shown to transport S1P) can also
suppress dystrophic muscle degeneration. Finally, administration to adult flies
of pharmacological agents reported to elevate S1P signaling significantly
suppresses dystrophic muscle phenotypes. Our data suggest that localized
intracellular S1P elevation promotes the suppression of muscle wasting in flies.
PMID- 23154415
TI - Otx2 is an intrinsic determinant of the embryonic stem cell state and is required
for transition to a stable epiblast stem cell condition.
AB - Mouse embryonic stem cells (ESCs) represent the naive ground state of the
preimplantation epiblast and epiblast stem cells (EpiSCs) represent the primed
state of the postimplantation epiblast. Studies have revealed that the ESC state
is maintained by a dynamic mechanism characterized by cell-to-cell spontaneous
and reversible differences in sensitivity to self-renewal and susceptibility to
differentiation. This metastable condition ensures indefinite self-renewal and,
at the same time, predisposes ESCs for differentiation to EpiSCs. Despite
considerable advances, the molecular mechanism controlling the ESC state and
pluripotency transition from ESCs to EpiSCs have not been fully elucidated. Here
we show that Otx2, a transcription factor essential for brain development, plays
a crucial role in ESCs and EpiSCs. Otx2 is required to maintain the ESC
metastable state by antagonizing ground state pluripotency and promoting
commitment to differentiation. Furthermore, Otx2 is required for ESC transition
into EpiSCs and, subsequently, to stabilize the EpiSC state by suppressing, in
pluripotent cells, the mesendoderm-to-neural fate switch in cooperation with BMP4
and Fgf2. However, according to its central role in neural development and
differentiation, Otx2 is crucially required for the specification of ESC-derived
neural precursors fated to generate telencephalic and mesencephalic neurons. We
propose that Otx2 is a novel intrinsic determinant controlling the functional
integrity of ESCs and EpiSCs.
PMID- 23154414
TI - MicroRNAs downregulate Bag of marbles to ensure proper terminal differentiation
in the Drosophila male germline.
AB - In many adult stem cell lineages, the continuous production of functional
differentiated cells depends on the maintenance of progenitor cells in an
undifferentiated and proliferative state, as well as the subsequent commitment to
proper terminal differentiation. In the Drosophila male germline stem cell (GSC)
lineage, a key differentiation factor, Bag of marbles (Bam), is required for the
transition from proliferative spermatogonia to differentiating spermatocytes. We
show that bam mRNA, but not Bam, is present in spermatocytes, suggesting that bam
is regulated post-transcriptionally. Consistent with this, repression of Bam
accumulation is achieved by microRNAs via the bam 3'UTR. When the bam 3'UTR was
substituted with the 3'UTR of a constitutively expressed alpha-Tubulin, Bam
became stabilized in spermatocytes. Moreover, such a persistent expression of Bam
in spermatocytes was recapitulated by specifically mutating the putative miR
275/miR-306 recognition site at the bam 3'UTR. In addition, overexpression of miR
275 or miR-306 in spermatogonial cells resulted in a delay of the proliferation
to-differentiation transition and resembled the bam loss-of-function phenotype,
suggesting that these microRNAs are sufficient to downregulate Bam. Finally, the
failure of Bam downregulation in spermatocytes affected spermatid terminal
differentiation and resulted in increased male sterility. Our results demonstrate
that microRNAs control the stem cell differentiation pathway through regulating
Bam, the downregulation of which is crucial for proper spermatid terminal
differentiation.
PMID- 23154416
TI - Protein tyrosine phosphatase 1B restrains mammary alveologenesis and secretory
differentiation.
AB - Tyrosine phosphorylation plays a fundamental role in mammary gland development.
However, the role of specific tyrosine phosphatases in controlling mammary cell
fate remains ill defined. We have identified protein tyrosine phosphatase 1B
(PTP1B) as an essential regulator of alveologenesis and lactogenesis. PTP1B
depletion increased the number of luminal mammary progenitors in nulliparous
mice, leading to enhanced alveoli formation upon pregnancy. Mechanistically,
Ptp1b deletion enhanced the expression of progesterone receptor and
phosphorylation of Stat5, two key regulators of alveologenesis. Furthermore,
glands from Ptp1b knockout mice exhibited increased expression of milk proteins
during pregnancy due to enhanced Stat5 activation. These findings reveal that
PTP1B constrains the number of mammary progenitors and thus prevents
inappropriate onset of alveologenesis in early pregnancy. Moreover, PTP1B
restrains the expression of milk proteins during pregnancy and thus prevents
premature lactogenesis. Our work has implications for breast tumorigenesis
because Ptp1b deletion has been shown to prevent or delay the onset of mammary
tumors.
PMID- 23154417
TI - The catalytic subunit of Arabidopsis DNA polymerase alpha ensures stable
maintenance of histone modification.
AB - Mitotic inheritance of identical cellular memory is crucial for development in
multicellular organisms. The cell type-specific epigenetic state should be
correctly duplicated upon DNA replication to maintain cellular memory during
tissue and organ development. Although a role of DNA replication machinery in
maintenance of epigenetic memory has been proposed, technical limitations have
prevented characterization of the process in detail. Here, we show that
INCURVATA2 (ICU2), the catalytic subunit of DNA polymerase alpha in Arabidopsis,
ensures the stable maintenance of repressive histone modifications. The missense
mutant allele icu2-1 caused a defect in the mitotic maintenance of vernalization
memory. Although neither the recruitment of CURLY LEAF (CLF), a SET-domain
component of Polycomb Repressive Complex 2 (PRC2), nor the resultant deposition
of the histone mark H3K27me3 required for vernalization-induced FLOWERING LOCUS C
(FLC) repression were affected, icu2-1 mutants exhibited unstable maintenance of
the H3K27me3 level at the FLC region, which resulted in mosaic FLC de-repression
after vernalization. ICU2 maintains the repressive chromatin state at additional
PRC2 targets as well as at heterochromatic retroelements. In icu2-1 mutants, the
subsequent binding of LIKE-HETEROCHROMATIN PROTEIN 1 (LHP1), a functional homolog
of PRC1, at PRC2 targets was also reduced. We demonstrated that ICU2 facilitates
histone assembly in dividing cells, suggesting a possible mechanism for ICU2
mediated epigenetic maintenance.
PMID- 23154419
TI - Evaluation of the chondroprotective effects of glucosamine and fish collagen
peptide on a rabbit ACLT model using serum biomarkers.
AB - The aim of this study was to investigate the correlations of severity of
osteoarthritis (OA) and serum biomarkers including keratan sulfate (KS),
hyaluronic acid (HA) and chondroitin sulfate (CS) 846 epitope. We also
investigated the effect of glucosamine and fish collagen peptide (FCP) on OA. OA
was induced in 12 rabbits (12 weeks of age) by anterior cruciate ligament
transection (ACLT). After the surgery, the rabbits were orally administered FCP
(F group), glucosamine (G group) or FCP and glucosamine (FG group) for 4 weeks.
The control group was provided water ad libitum (C group). Blood was collected
before surgery (pre-ACLT) and before euthanasia (post-ACLT) for serum marker
measurement. Biomarker levels were measured by using commercial kits. We
evaluated OA severity both macroscopically and histologically. Macroscopic
evaluation showed mildly eroded condylar surfaces in the C group. Histological
findings were significantly different from the FG and other groups. There were no
significant differences between each group at post-ACLT in terms of serum KS, HA
and CS 846. Histological assessment and serum biomarker measurements performed at
post-ACLT showed a significant correlation between HA concentration and OA
severity. Variations in the CS 846 concentration at pre-ACLT and post-ACLT were
significantly correlated with OA severity. Administration of glucosamine and FCP
had chondroprotective effects in the ACLT model. Serum biomarker concentrations
were significantly correlated with cartilage injury. Serum biomarker measurement
would be useful for monitoring articular cartilage damage in the clinical
setting.
PMID- 23154418
TI - MEF2A regulates the Gtl2-Dio3 microRNA mega-cluster to modulate WNT signaling in
skeletal muscle regeneration.
AB - Understanding the molecular mechanisms of skeletal muscle regeneration is crucial
to exploiting this pathway for use in tissue repair. Our data demonstrate that
the MEF2A transcription factor plays an essential role in skeletal muscle
regeneration in adult mice. Injured Mef2a knockout mice display widespread
necrosis and impaired myofiber formation. MEF2A controls this process through its
direct regulation of the largest known mammalian microRNA (miRNA) cluster, the
Gtl2-Dio3 locus. A subset of the Gtl2-Dio3 miRNAs represses secreted Frizzled
related proteins (sFRPs), inhibitors of WNT signaling. Consistent with these
data, Gtl2-Dio3-encoded miRNAs are downregulated in regenerating Mef2a knockout
muscle, resulting in upregulated sFRP expression and attenuated WNT activity.
Furthermore, myogenic differentiation in Mef2a-deficient myoblasts is rescued by
overexpression of miR-410 and miR-433, two miRNAs in the Gtl2-Dio3 locus that
repress sFRP2, or by treatment with recombinant WNT3A and WNT5A. Thus, miRNA
mediated modulation of WNT signaling by MEF2A is a requisite step for proper
muscle regeneration, and represents an attractive pathway for enhancing
regeneration of diseased muscle.
PMID- 23154420
TI - Early onset of reproductive function in female rats treated with a high-fat diet.
AB - Puberty onset in mammals is tightly coupled to the animal's nutritional and
metabolic state. In the present study, we evaluated the effects of a high-fat
diet on leptin and adiponectin levels, leptin mRNA expression and puberty onset
in female rats. On day 21, female rats were divided into 2 groups, normal food
(NF) and high-fat food (HF). The HF group showed a significantly earlier
(P<0.001) date of vaginal opening and lower body weight (P<0.001) than the NF
group. The rats fed the HF food had a significantly heavier uterus (P<0.05) than
those fed the NF food, whereas the serum leptin and adiponectin levels and leptin
mRNA expression were not significantly different between the NF and HF groups. We
speculate that the fat-induced nutritional imbalance in young females may lead to
neuroendocrine dysfunction during adolescence.
PMID- 23154421
TI - ADAMTS: novel proteases expressed by activated mast cells.
AB - Here we show that mast cells (MCs) express the metalloproteases of the A
disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family, and
that ADAMTS expression is influenced by MC activation. Co-culture of MCs with
live Gram-positive bacteria caused a profound induction of ADAMTS-9 and -6, as
well as down-regulated expression of ADAMTS-5. Similar patterns were also seen
after MC activation with calcium ionophore and by immunoglobulin E receptor
crosslinking. Moreover, ADAMTS-5, -6 and -9 were all induced by activation of
terminally differentiated murine peritoneal MCs and in a human MC line. ADAMTS-9
up-regulation in response to immunoglobulin E receptor crosslinking was strongly
dependent on Go6976-sensitive protein kinase C and partly dependent on nuclear
factor of activated T cells and nuclear factor kappa-light-chain-enhancer of
activated B cells, respectively. The expression of ADAMTS-5, -6 and -9 was
closely linked to MC maturation, as shown by their strong induction during the
differentiation of bone marrow precursor cells into mature MCs. ADAMTS family
members have been shown to possess aggrecanase activity. Accordingly, MCs were
shown to express aggrecanase activity. Finally, ADAMTS-5 protein was detected in
MCs by immunocytochemistry. Taken together, the present study reveals ADAMTS
expression by MCs and that MC activation regulates the expression of these
proteases, thus implicating the ADAMTS family of proteases in MC function.
PMID- 23154423
TI - Evaluation of [-2] proPSA and Prostate Health Index (phi) for the detection of
prostate cancer: a systematic review and meta-analysis.
AB - The usefulness of %[-2] proPSA and Prostate Health Index (phi) in the detection
of prostate cancer are currently unknown. It has been suggested that these tests
can distinguish prostate cancer from benign prostatic diseases better than PSA or
%fPSA. We performed a systematic review and meta-analysis of the available
scientific evidence to evaluate the clinical usefulness of %[-2] proPSA and phi.
Relevant published papers were identified by searching computerized bibliographic
systems. Data on sensitivity and specificity were extracted from 12 studies: 10
studies about %[-2] proPSA (3928 patients in total, including 1762 with confirmed
prostate cancer) and eight studies about phi (2919 patients in total, including
1515 with confirmed prostate cancer). The sensitivity for the detection of
prostate cancer was 90% for %[-2] proPSA and phi, while the pooled specificity
was 32.5% (95% CI 30.6-34.5) and 31.6% (95% CI 29.2-34.0) for %[-2] proPSA and
phi, respectively. The measurement of %[-2] proPSA improves the accuracy of
prostate cancer detection in comparison with PSA or %fPSA, particularly in the
group of patients with PSA between 2 MUg/L and 10 MUg/L. Similar results were
obtained measuring phi. Using these tests, it is possible to reduce the number of
unnecessary biopsies, maintaining a high cancer detection rate. Published results
also showed that %[-2] proPSA and phi are related to the aggressiveness of the
tumor.
PMID- 23154424
TI - Association and prognostic value of serum inflammation markers in patients with
leukoplakia and oral cavity cancer.
AB - BACKGROUND: Oral cavity cancer ranks as the fourth leading cancer in men in
Taiwan. The development of a serum biomarker panel for early detection and
disease monitoring is, therefore, warranted. METHODS: Nine inflammation
associated markers were investigated in 46 patients with leukoplakia, 151
patients with untreated oral cavity squamous cell carcinoma (OSCC), and 111 age-
and gender-matched healthy controls using enzyme-linked immunosorbent assay.
During a subsequent 28-month surveillance of OSCC patients, serum samples were
prospectively collected at predetermined intervals following the completion of
therapy. RESULTS: Logistic regression analysis showed matrix metalloproteases
(MMP)-2, MMP-9, C-reactive protein (CRP), transforming growth factor-beta1 (TGF
beta1), and E-selectin having the best discrimination power between groups and
significant elevation trends of those five markers were noted from control to
OSCC. By combining those five markers, a 0.888 and 0.938 area under curve by ROC
curve analysis with 67.4% and 80% overall sensitivity and fixed 90% specificity
for leukoplakia and OSCC groups were demonstrated. In the follow-up period, 25
OSCC patients developed recurring or secondary tumors. All examined markers had
decreased in relapse-free patients following treatment. However, in patients with
relapse, interleukin-6, CRP, and serum amyloid A remained at elevated levels.
Statistical analysis showed that patients with CRP ?2 mg/L and E-selectin ?85
ng/mL at baseline had highest probability of relapse (odds ratio=3.029, p<0.05).
CONCLUSIONS: The results indicate that inflammation plays a crucial role in the
pathogenesis process of OSCC. By examining the inflammation markers, physicians
could potentially identify patients at risk of cancer transformation or relapse.
PMID- 23154425
TI - Homocysteine and alpha-1 antitrypsin concentration in patients with subclinical
hypercortisolemia.
AB - PURPOSE: Glucocorticoids have particularly strong impact on the thromboembolic
complications. A factor which increases the risk of thrombosis is
hyperhomocysteinemia, observed in patients with hypercortisolemia.
Proinflammatory factors also affect the haemostatic balance. There has been an
extensive research which estimates hemostatic system in patients with Cushing's
syndrome. Undoubtedly, much fewer publications are available on thromboembolic
complications in patients with Subclinical Cushing's Syndrome (SCS). The purpose
of this study was to estimate of homocysteine (HCY) and alpha-1 antitrypsin
(alpha1ATp) concentrations in patients with SCS. MATERIALS AND METHODS: We
studied 35 patients (56.0 +/- 15.0 years) with SCS and 33 healthy volunteers
(53.3 +/- 17.7 years). In all subjects the analysis of HCY and alpha1ATp
concentration in serum was determined with an immunonephelometric method. P
values below 0.05 were considered statistically significant. RESULTS: A
comparison of HCY and alpha1ATp mean concentrations in patients with SCS and
healthy representatives indicated statistically higher values of both analysed
parameters in the sera of patients than in the healthy controls (p values were
0.018 and 0.008, respectively). In the patients with SCS a negative correlation
between alpha1ATp and cortisol concentration in overnight dexamethasone test was
found (p=0.017, R=-0.40). We did not reveal any statistically significant
correlation between the concentrations of HCY and alpha1ATp, and coagulation
parameters such as INR, APTT, fibrinogen concentration in patients with SCS.
CONCLUSIONS: On the basis of the obtained results, a slight increase in the
concentration of homocysteine and alpha1ATp is observed in patients with SCS,
which may influence vascular complications.
PMID- 23154422
TI - Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy.
AB - Muscle loss during aging and disuse is a highly prevalent and disabling
condition, but knowledge about cellular pathways mediating muscle atrophy is
still limited. Given the postmitotic nature of skeletal myocytes, the maintenance
of cellular homeostasis relies on the efficiency of cellular quality control
mechanisms. In this scenario, alterations in mitochondrial function are
considered a major factor underlying sarcopenia and muscle atrophy. Damaged
mitochondria are not only less bioenergetically efficient, but also generate
increased amounts of reactive oxygen species, interfere with cellular quality
control mechanisms, and display a greater propensity to trigger apoptosis. Thus,
mitochondria stand at the crossroad of signaling pathways that regulate skeletal
myocyte function and viability. Studies on these pathways have sometimes provided
unexpected and counterintuitive results, which suggests that they are organized
into a complex, heterarchical network that is currently insufficiently
understood. Untangling the complexity of such a network will likely provide
clinicians with novel and highly effective therapeutics to counter the muscle
loss associated with aging and disuse. In this review, we summarize the current
knowledge on the mechanisms whereby mitochondrial dysfunction intervenes in the
pathogenesis of sarcopenia and disuse atrophy, and highlight the prospect of
targeting specific processes to treat these conditions.
PMID- 23154426
TI - Cytotoxicity evaluation of three light-cured dentin adhesive materials on human
gingival fibroblasts, ex vivo.
AB - PURPOSE: To evaluate the cytotoxic effects of three current light-cured dentin
adhesives, in both uncured and post-cured conditions, on human gingival
fibroblasts. MATERIAL AND METHODS: The materials tested were Heliobond, Adper
Single Bond 2 and Xeno V, which are characterized by various compositions and
application procedures. Each agent, in volumes of 5 and 10 MUL, was tested after
polymerization, and those unpolymerized were diluted in DMEM to 10-3 and 10-5.
The cytotoxicity of the adhesives was assessed on the basis of a test of cell
viability in a culture of human gingival fibroblasts, with the use of tetrazolic
salt (MTT assay). RESULTS: The results showed that, among the adhesive/bonding
systems tested, Xeno V was the least cytotoxic. There were statistically
significant differences in cell survival between polymerized Xeno V, Adper Single
Bond 2 and Heliobond in the amount of 5 MUL as well as between the Xeno V and
Adper Single Bond 2 in 10-5 dilutions. The tested adhesives were more toxic in
the polymerized form than in the dilutions. Samples of 10 MUL resulted in a lower
survival percentage of fibroblasts compared to 5 MUL. CONCLUSION: All the tested
adhesives demonstrated cytopathic effects towards human gingival fibroblasts, but
varied in their cytotoxicity. This has clinical implications. Dentists should
follow the rules of adhesive application, precisely dose them and not allow
direct contact with the gums as, even after polymerization, adhesive agents
exhibit potential cytotoxic activity.
PMID- 23154427
TI - Magnetic nanoparticles as new diagnostic tools in medicine.
AB - Magnetic iron oxide nanoparticles have raised much interest during the recent
years due to their novel properties (superparamagnetism, high saturation field,
blocking temperature, etc.) and potential applications in organic synthesis,
biotechnology and finally in medicine. The medicinal applications include:
controlled drug delivery systems (DDS), magnetic resonance imaging (MRI),
magnetic fluid hyperthermia (MFH), macromolecules and pathogens separation,
cancer therapy and so on. In this paper we would like to present the newest
literature reports concerning usage of MNPs in medicinal diagnostics such as: -
magnetic separations of DNA (immobilization, isolation, diagnosis of genetic
disorders and detection of exogenous substances in the organisms) - magnetic
immobilization of proteins (applications in biotechnology, medicine, and
catalysis) - magnetic separations of pathogens (i.e. isolation of bacteria,
detection of various pathogens) - magnetic resonance imaging (imaging contrast
agents, lymphangiography).
PMID- 23154428
TI - Evidence that FGFR1 loss-of-function mutations may cause variable skeletal
malformations in patients with Kallmann syndrome.
AB - PURPOSE: Loss-of-function mutations in FGFR1 have been identified in
approximately 10% of the Kallmann syndrome (KS) patients. Previous reports have
focused mainly on olfactory, reproductive, and some other features such as cleft
lip/palate and dental agenesis. Given the ubiquitous expression of FGFR1 during
development, other abnormal phenotypes might, however, have been overlooked in
these patients. Here, we demonstrate skeletal phenotypic characterization of
patients presented with KS and FGFR1 mutations. MATERIAL AND METHODS: Using the
Sanger DNA sequencing technique a cohort of 29 KS patients was screened. RESULTS:
Here, we report on 5 KS patients who carry FGFR1 mutations (Gly270Asp, Gly97Ser,
Met161Thr, Ser685Phe and Ala167Ser/Ala167Ser). Three patients presented with
skeletal abnormalities, i.e. spine (hemivertebra and butterfly vertebra) and limb
(oligodactyly of the feet, fusion of the 4th and 5th metacarpal bones)
malformations in two patients and one patient, respectively. The hand phenotype
found in the patient cannot be thought of as a counter-type of the hand phenotype
resulting from FGFR1 gain-of-function mutations. The skeletal anomalies
identified in the 3 KS patients are close to those observed in Fgfr1 conditional
knockout mice. CONCLUSIONS: This study demonstrates that FGFR1 loss-of-function
mutations can be associated with skeletal abnormalities also in humans. Further
investigations in KS patients who carry FGFR1 mutations are needed to evaluate
the prevalence of skeletal defects in this genetic form of KS. Conversely, the
presence of bone malformations in a KS patient should direct the geneticist
towards a search for mutations in FGFR1.
PMID- 23154429
TI - Intellectual functioning of childhood leukemia survivors--relation to Tau protein
-a marker of white matter injury.
AB - PURPOSE: Chemo- and radiotherapy used in acute lymphoblastic leukemia (ALL) can
influence on brain functioning in the future. In a prospective study we analysed
the cognitive functions of ALL survivors in relation to Tau protein as a marker
of white matter injury. MATERIAL AND METHODS: Thirty-one survivors of childhood
ALL (6.3 years after diagnosis); without the signs of CNS involvement, treated
with chemotherapy alone, rested in first remission; underwent Intelligence tests-
Wechsler Intelligence Scales (WISC-R, WAIS-R). Their results were analyzed in
relation to the levels of Tau in cerebrospinal fluid (CSF) obtained during the
treatment. RESULTS: The analysis showed that all survivors attained the average
scores in intelligence tests. A negative correlation was found between
methotrexate (MTX) doses and Freedom from Distractibility (FFD). Females had
higher values of Performance Intelligence Quotient (PIQ) than males. A negative
correlation was noted of Tau protein levels obtained from the last CSF with:
Total and Verbal Intelligence Quotient, PIQ, Perceptual Organisation Index and
FFD but not with Verbal Comprehension Index. CONCLUSION: Our results suggest the
possibility of white matter injury during the treatment for ALL with chemotherapy
alone. Elevated Tau protein level in CSF at the end of treatment might indicate
future difficulties in neurocognitive functioning.
PMID- 23154430
TI - Behavioral and psychological symptoms of dementia: factor analysis and
relationship with cognitive impairment.
AB - BACKGROUND/AIMS: Behavioral and psychological symptoms of dementia (BPSD) affect
almost all people with dementia at some stage during the progression of disease.
The current study aimed at replicating previous findings on BPSD clustering in
behavioral sub-syndromes. METHODS: One hundred and sixty-six consecutive
outpatients with dementia attending a dementia outpatient clinic were enrolled
and evaluated with the Neuropsychiatric Inventory and the Mini Mental State
Examination. RESULTS: BPSD were reported in 157 patients included in the final
sample: 140 patients (89.17%) had Alzheimer's disease (AD), while 17 patients had
frontotemporal dementia or vascular dementia. The most frequent BPSD were
depression in the whole sample and irritability in the AD subgroup. The severity
of cognitive impairment was predicted by two BPSD in the whole sample (apathy and
motor disturbance) and only by nighttime behavior in the AD subgroup. Factor
analyses identified 4 factors, accounting for about 60% of variance in the whole
group and in the AD subgroup of patients. CONCLUSIONS: The current study
confirmed findings of previous studies on BPSD clustering, regarding the number
of BPSD clusters and the total variance explained. This study has some
limitations, including the small number of non-ADs and its monocentric character.
PMID- 23154432
TI - TLR7 contributes to the rapid progression but not to the overall fatal outcome of
secondary pneumococcal disease following influenza A virus infection.
AB - Increased risk for bacterial superinfections substantially contributes to the
mortality caused by influenza A virus (IAV) epidemics. While the mechanistic
basis for this lethal synergism is still insufficiently understood, immune
modulation through the viral infection has been shown to be involved. Since the
pattern-recognition receptor (PRR) toll-like receptor 7 (TLR7) is a major sensor
for the viral genome, we studied how IAV recognition by TLR7 influences the
development of secondary pneumococcal infection. In a mouse model of IAV, TLR7
deficient hosts induced a potent antiviral response and showed unchanged
survival. In secondary pneumococcal infection during acute influenza, TLR7ko mice
showed a fatal outcome similar to wild-type (WT) hosts, despite significantly
delayed disease progression. Also, when bacterial superinfection occurred after
virus clearance, WT and TLR7-deficient hosts showed similar mortality, even
though we found the phagocytic activity of alveolar macrophages isolated from IAV
pre-infected hosts to be enhanced in TLR7ko over WT mice. Thus, we show that a
virus-sensing PRR modulates the progression of secondary pneumococcal infection
following IAV. However, the fatal overall outcome in WT as well as TLR7ko hosts
suggests that processes distinct from TLR7-triggering override the contribution
of this single PRR.
PMID- 23154431
TI - Blockade of inhibitors of apoptosis (IAPs) in combination with tumor-targeted
delivery of tumor necrosis factor-alpha leads to synergistic antitumor activity.
AB - In the current study, we examined whether the combination of tumor vasculature
targeted gene therapy with adeno-associated virus bacteriophage-tumor necrosis
factor-alpha (AAVP-TNF-alpha) and/or the orally administered LCL161, an
antagonist of inhibitors of apoptosis proteins (IAPs), enhanced antitumor
efficacy without systemic toxicity. M21 human melanoma xenografts were grown
subcutaneously in nude mice. Mice were treated according to one of four treatment
regimens: AAVP-TNF-alpha alone (AAVP-TNF-alpha plus sodium acetate-acetic acid
(NaAc) buffer) via tail vein injection; LCL161 alone (phosphate-buffered saline
(PBS) plus LCL161) via oral gavage; AAVP-TNF-alpha plus LCL161; and PBS plus NaAc
Buffer as a control group. Tumor volume, survival and toxicity were analyzed.
AAVP trafficking and TNF-alpha production in vivo were detected on days 7 and 21
by real-time PCR, enzyme-linked immunosorbent assay and immunofluorescence. The
levels of apoptosis and activation of caspases were assessed on days 7 and 21 by
TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling) and
immunofluorescence assays. Our results showed that the combination of AAVP-TNF
alpha and LCL161 significantly inhibited tumor growth and prolonged survival in
mice with melanoma xenografts. The combination of AAVP-TNF-alpha and LCL161 was
also significantly more effective than either agent alone, showing a synergistic
effect without systemic toxicity.
PMID- 23154433
TI - Metallic nanoparticles enhanced the spontaneous emission of semiconductor
nanocrystals embedded in nanoimprinted photonic crystals.
AB - We report on a method to enhance the light-emission efficiency of printable thin
films of a polymer doped with luminescent (CdSe)ZnS nanocrystals via metallic
nanoparticles and nanoimprinted photonic crystals. We experimentally show a
strong fluorescence enhancement of nanocrystals by coupling exciton-plasmon with
the localized surface plasmon of metallic nanoparticles. The emitted light is
efficiently diffracted by photonic crystals structures directly imprinted in the
nanocomposite polymer. By combining the field susceptibility technique with
optical Bloch equations, we examine the interaction of the quantum and plasmonic
entities at small distances.
PMID- 23154434
TI - Changes in circulating pro-angiogenic cytokines, other than VEGF, before
progression to sunitinib therapy in advanced renal cell carcinoma patients.
AB - OBJECTIVES: This study included a cohort of advanced renal cell carcinoma
patients treated with sunitinib. Since resistance to sunitinib may be mediated
through angiogenic cytokines other than VEGF, we measured the circulating levels
of three pro-angiogenic cytokines: basic fibroblast growth factor (bFGF),
hepatocyte growth factor (HGF), and interleukin (IL)-6. METHODS: Cytokines were
measured at baseline and on the first day of each treatment cycle until
progression in 85 advanced kidney cancer patients treated with sunitinib using a
quantitative sandwich enzyme immunoassay (ELISA) technique. RESULTS: Even though
no statistically significant differences in the titers of the three cytokines
were observed between baseline and the time of progression in the whole patient
cohort, in 45.3, 46.6, and 37.3% of the patients a more than 50% increase between
baseline and the time of progression was shown in circulating IL-6, bFGF, and
HGF, respectively. Furthermore, this increase was more than 100% in 37.3, 44, and
30.6% of the patients, respectively. We also demonstrated that, in these
patients, cytokines tended to increase and to remain high immediately before
progression. CONCLUSIONS: In a large percentage of kidney cancer patients,
progression is preceded by a significant increase in pro-angiogenic cytokines
other than VEGF.
PMID- 23154435
TI - A model-based survey of physical health in community-dwelling older adults.
AB - BACKGROUND: Having a better comprehension of older adults' physical health can
help healthcare professionals better design program activities to maintain and
promote the health of this population. PURPOSE: This study investigated the
physical health of community-dwelling older adults and compared physical health
differences among different age subgroups, gender, and exercise habits. METHODS:
Using stratified random sampling, 384 Taiwanese community-dwelling older adults
were recruited in this survey research. Researchers used the Health Model of
Older Adults to measure activities of daily living (6 indicators) and physical
status (14 indicators). Analysis of variance and independent t test analyzed the
data. RESULTS: Most participant physical health indicators were within normal
ranges. Exceptions included central obesity (men: 42.90%, women: 80.30%),
abnormal blood pressure (systolic: 47.10%, diastolic: 7%), and deteriorated lung
capacity (men: 59.30%, women: 70.70%). Young-old subgroup participants (65-74
years old) and exercisers performed better in their activities of daily living
and had better physical status than old-old subgroup participants (> 85 years
old) and nonexercisers (all p < .05). Men had better physical status than women
(all p < .05). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Maintaining an active
lifestyle and exercising regularly are essential to delaying or preventing the
deterioration of natural aging. Physical tolerance, functional ability,
educational level, and gender differences should be considered when designing a
health promotion program for this population. It is essential for national health
policy to enhance older adult health and promote active and healthy aging.
PMID- 23154436
TI - Predictors of sleep quality in community-dwelling older adults in Northern
Taiwan.
AB - BACKGROUND: Poor sleep quality may have a significant and negative impact on
physical and mental health. Poor sleep quality also increases the risk of all
cause mortality. Few studies have explored the sleep quality of community
dwelling older adults in Taiwan. PURPOSE: This study examined the prevalence of
sleep disturbance and potential factors of influence in community-dwelling older
people in Taiwan. METHODS: We used a cross-sectional design to recruit a total of
160 individuals 60 years of age or older from an urban area in northern Taiwan.
All subjects completed a structured questionnaire that included demographic data,
physical health status, a social activity/habit survey, as well as the Chinese
versions of Barthel's index, Pittsburgh Sleep Quality Index, short form of the
Geriatric Depression Scale, the SF-36 Health-Related Quality of Life Survey, and
the Physical Activity Scale for the Elderly. RESULTS: Participants reported a
rate of sleep disturbance of 41.9%. Sleep disturbance was associated with
nocturia and dizziness, hypertension, increased use of medications such as
antihypertensives and gastric medicines, poor self-reported functional status,
depression, and sedentary lifestyle. Logistic regression showed nocturia,
sedentary lifestyle, and mental component summary score as significant predictors
of sleep disturbance. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Sleep disturbance
should be examined within the context of an individual's physical, mental, and
social status. Symptom management education and an active lifestyle are necessary
to promote sleep quality in older people.
PMID- 23154437
TI - Development of frailty indicators for the community-dwelling older adults.
AB - BACKGROUND: Faster than anticipated increases in population, aging is making the
issue of frailty among the elderly increasingly important. Despite general
agreement that a frailty assessment is important for planning care for the older
adults, a lack of consensus remains regarding the best methodology to use for
frailty assessments. PURPOSE: The aim of this study was first to cross-examine
results between perception of frailty and physical assessment outcomes then try
to establish frailty indicators for elderly people in Taiwan. METHODS: This study
used both qualitative and quantitative methods. From August to September 2010,
researchers recruited a convenience sample of 10 community older adults from six
different elderly centers in northern Taiwan. Qualitative in-depth interviews
were conducted in Mandarin or Taiwanese and audiotaped. After the in-depth
interview, researchers conducted a series of physical assessments on the
participants. RESULTS: Ten elderly women were interviewed and assessed. The three
themes identified by this study related to frailty perception included overall
physical function performance, psychological health, and physiological health.
These reflected the concept of successful aging. Participant frailty was compared
with subjective perceptions to identify and/or check for consistency between
qualitative and quantitative results. Although quantitative results revealed that
participants were in fairly good health, there were many complaints about frailty
during the qualitative interview. Better sensitive measures reflecting frailty
changes are thus needed. CONCLUSIONS: These indicators can be considered as an
integration of all maintained functions. We hope that results will provide better
insights into understanding the process of frailty among the older adults.
PMID- 23154438
TI - Nonimaging clinical assessment of impaired swallowing in community-dwelling older
adults in Taiwan.
AB - BACKGROUND: Impaired swallowing is common in elderly patients as well as those
with neurological disorders and degenerative diseases. Convenient and accurate
assessments should be available to community-dwelling older adults to diagnose
and provide early management and care of swallowing difficulties, an important
factor of influence on elderly life quality. PURPOSE: This study used convenient
nonimaging methods to assess swallowing functions in community-dwelling older
adults and estimated the prevalence of swallowing difficulties. METHODS: The
study adopted a survey method and recruited 216 community-dwelling older adults
over 65 years old in northern Taiwan. Researchers used tools including a
swallowing test, questionnaire, water test, peripheral arterial pulse oximeter,
and laryngeal S-EMG to assess participant swallowing functions and the prevalence
of impaired swallowing. RESULTS: We found a 9.5% prevalence of impaired
swallowing based on swallow questionnaire and water test results. Age correlated
negatively with swallowing speed. A one-way ANOVA showed a significant difference
in swallowing speed among the four age groups (F = 6.478, p < .00). A post hoc
Scheffe comparison showed significant differences in swallowing time between the
60- to 69- and 70- to 79-year-old groups and 60- to 69- and 80- to 89-year-old
groups. Multiple regression of impaired swallowing on various independent
variables showed a significant standardized coefficient of 0.163 for age (t =
2.328, p = .021). Logistic regression showed a significant Wals test value for
age (p = .007). The Kappa value was 0.307 for agreement analysis between impaired
swallowing and SaO(2) value reduction of more than 2%. CONCLUSIONS/IMPLICATIONS
FOR PRACTICE: Swallowing function deteriorates with age. Results of this study
provide an assessment of the prevalence of impaired swallowing in community
dwelling older adults in Taiwan. Results can help guide clinical nurses to
enhance their objective assessment of impaired swallowing to improve patient
quality of life.
PMID- 23154439
TI - The effects of a spiritual learning program on improving spiritual health and
clinical practice stress among nursing students.
AB - BACKGROUND: Numerous studies have indicated an association between spirituality
and health outcomes. However, little information is available about interventions
that have been shown to enhance spiritual health and decrease stress. PURPOSE:
This study examined the effects of a spiritual learning program (SLP) on nursing
student-perceived spiritual health and clinical practice stress. METHOD: A
convenience sample of nursing students currently enrolled at a nursing school in
northern Taiwan were recruited to participate in this quasiexperimental study as
participants to experimental and control groups via simple random sampling.
Results from a spiritual health scale and a perceived clinical practice stress
scale, together with the score for clinical nursing practice, were compared
between the groups. Baseline data were collected from all participants. The
experimental group participated in 8 weeks of 50-minute per week SLP, which
included lectures, discussion, reflection, and spiritual practices. A second data
set was collected from all participants after the intervention. A third data set
was collected after all participants had performed 4 weeks of nursing clinical
practice. RESULTS: Participants were all women. Average age was 19.4 years (SD =
1.3 years). Generalized estimating equation analysis showed SLP to have a
significant short-term effect on improving the total score for spiritual health
(p < .01). Significantly greater improvement in clinical practice stress scores
was also seen in the experimental group as compared with the control group (all p
< .05). The experimental group obtained a higher score of the final clinical
practice than the control group (t = 3.771, p < .001). CONCLUSION: The SLP may
encourage participants to see stressors as meaningful events that are connected
to individual life purposes. The program developed in this study may be used to
improve spiritual health and reduce stress in nursing students' clinical
practice. This SLP may be referenced when designing similar spirituality-related
courses and applied to nursing student counseling.
PMID- 23154440
TI - Qualitative assessment of a blended learning intervention in an undergraduate
nursing course.
AB - BACKGROUND: Nurses are experiencing new ethical issues because of global
developments and changes in the healthcare environment. Blended learning is one
of the various methods used to deliver meaningful learning experiences. Well
designed, properly administered nursing ethics education is essential for nursing
students to visualize the role of professional nurses. However, a literature
review shows that only a few existing studies have touched on the subject of
nursing student experiences with blended learning in a nursing ethics course.
PURPOSE: This study examines how undergraduate nursing students respond to a
blended learning approach in a nursing ethics course and how blended learning
affects the learning process. METHODS: We used a qualitative research design with
in-depth interviews. Participants included 28 female undergraduate nursing
students who had completed the nursing ethics course. Each interview lasted 50
100 minutes. The researcher conducted all interviews in 2009. RESULTS: The
researcher identified six major themes and 13 subthemes from the data. The six
themes included (a) enhancing thinking ability, (b) improving problem-solving
skills, (c) reflecting in and on practice, (d) perceiving added workload, (e)
encouraging active learning, and (f) identifying the value of nursing.
Participants felt that the blended learning experience was a generally positive
experience. CONCLUSION: Most participants appreciated the opportunity to take a
more active role in the learning process, think about issues profoundly and
critically, and exercise metacognitive powers in the thinking and decision-making
process. Study findings may suggest productive ideas for fine-tuning blended
learning models.
PMID- 23154441
TI - Exploring the association between nurse workload and nurse-sensitive patient
safety outcome indicators.
AB - BACKGROUND: Nurses affect patient safety. Although studies have associated
patient safety with nurse staffing levels, Taiwan's Department of Health does not
yet support changing nurse workforce standards for medical institutions. PURPOSE:
This study was designed to gain insight into the workload of nurses employed at
medical institutions and to determine the relationship between nurse workload and
nurse-sensitive patient safety outcome indicators. METHODS: This study adopted a
cross-sectional quantitative method and collected data using a self-designed
logbook. The study population comprised nurses from acute medical institutions,
including medical centers and regional and district hospitals. One thousand five
hundred logbooks were distributed to participants selected by random sampling
from 21 city/county nursing associations across Taiwan. One thousand three
hundred seventy-three questionnaires were retrieved; the 1,358 valid responses
yielded a valid response rate of 90.5%. Nurses used the logbook to record
individual working conditions for 2 weeks. Descriptive statistics included mean
values, standard deviations, and percentages; inferential statistics included the
Spearman rho correlation and odds ratios. RESULTS: Nurse overtime working hours
were positively associated with the following nurse-sensitive patient safety
outcome indicators: patient falls, decubitus/pressure ulcers, near errors in
medication, medication errors, unplanned extubation, hospital-acquired pneumonia,
and hospital-acquired urinary tract infections; risks of patient falls,
decubitus/pressure ulcers, unplanned extubation, hospital-acquired pneumonia, and
hospital-acquired urinary tract infections significantly increased when the
patient-nurse ratio exceeded 7:1. CONCLUSION: Nurse workforce and nurse-sensitive
patient outcome indicators are positively correlated. The results of this study
will help professional nursing groups define suitable nursing workforce standards
for medical institutions.
PMID- 23154442
TI - Psychological distress in women who have experienced intrauterine insemination.
AB - BACKGROUND: Despite evidence that psychological distress manifests itself in
underreported and atypical ways, few studies have assessed these symptoms in
women who have experienced intrauterine insemination (IUI). PURPOSE: The aim of
this study was to examine the prevalence of psychological distress and explore
the relationships among psychological distress, various demographic
characteristics, and somatic symptoms in women who had received IUI treatment in
Taiwan. METHODS: A cross-sectional study design was used in this study. The 117
participants were recruited from a teaching hospital in northern Taiwan. The
brief symptom rating scale (BSRS-5) was used as the measurement instrument, and
scores of more than 5 on the BSRS-5 were used to mark the boundary between milder
and more severe psychological distress. Demographic characteristics and somatic
symptoms of IUI that contributed most significantly to psychological distress
were identified from the data. RESULTS: Thirty-eight (32.5%) participants
experienced psychological distress. Psychological distress was most common in
participants (a) with husbands who were an only son, (b) who had taken medication
during the previous week, (c) with an education level below college or
university, and (d) who reported feeling faint. CONCLUSIONS/IMPLICATIONS FOR
PRACTICE: The factors studied are important to understand psychological distress
in women who have undergone IUI treatment.
PMID- 23154443
TI - Effect of PGX, a novel functional fibre supplement, on subjective ratings of
appetite in overweight and obese women consuming a 3-day structured, low-calorie
diet.
AB - INTRODUCTION: Dietary factors that help control perceived hunger might improve
adherence to calorie-reduced diets. OBJECTIVES: The objective of the study was to
investigate the effect of supplementing a three-day, low-calorie diet with
PolyGlycopleX (PGX), a highly viscous fibre, on subjective ratings of appetite
compared with a placebo. METHODS: In a double-blind crossover design with a 3
week washout, 45 women (aged 38+/-9 years, body mass index 29.9+/-2.8 kg m(-2))
were randomised to consume a 1000-kcal per day diet for 3 days, supplemented with
5 g of PGX or placebo at each of breakfast, lunch and dinner. Subjective appetite
was assessed using 100 mm visual analogue scales that were completed daily
before, between and after consumption of meals. RESULTS: Thirty-five women
completed the study. Consumption of PGX compared with placebo led to
significantly lower mean area under the curve for hunger on day 3 (440.4 versus
375.4; P=0.048), prospective consumption on day 3 (471.0 versus 401.8; P=0.017)
and the overall 3-day average (468.6 versus 420.2; P=0.026). More specifically,
on day 3 PGX significantly reduced total appetite, hunger, desire to eat and
prospective consumption for 2.5 and 4.5 h after lunch and before dinner times,
with hunger also being reduced 2.5 h after dinner (P<0.05). CONCLUSION: The
results show that adding 5 g of PGX to meals during consumption of a low-calorie
diet reduces subjective ratings of prospective consumption and increases the
feelings of satiety, especially during afternoon and evening. This highly viscous
polysaccharide may be a useful adjunct to weight-loss interventions involving
significant caloric reductions.
PMID- 23154446
TI - Thickness identification of two-dimensional materials by optical imaging.
AB - Two-dimensional materials, e.g. graphene and molybdenum disulfide (MoS(2)), have
attracted great interest in recent years. Identification of the thickness of two
dimensional materials will improve our understanding of their thickness-dependent
properties, and also help with scientific research and applications. In this
paper, we propose to use optical imaging as a simple, quantitative and universal
way to identify the thickness of two-dimensional materials, i.e. mechanically
exfoliated graphene, nitrogen-doped chemical vapor deposition grown graphene,
graphene oxide and mechanically exfoliated MoS(2). The contrast value can easily
be obtained by reading the red (R), green (G) and blue (B) values at each pixel
of the optical images of the sample and substrate, and this value increases
linearly with sample thickness, in agreement with our calculation based on the
Fresnel equation. This method is fast, easily performed and no expensive
equipment is needed, which will be an important factor for large-scale sample
production. The identification of the thickness of two-dimensional materials will
greatly help in fundamental research and future applications.
PMID- 23154445
TI - Phosphoproteomic analysis identifies insulin enhancement of discoidin domain
receptor 2 phosphorylation.
PMID- 23154447
TI - The effect of locked screw angulation on the biomechanical properties of the
S.P.S. Free-Block plate.
AB - OBJECTIVES: Among the locked internal fixators is one denominated S.P.S.
(Synthesis Pengo System) Free-Block, which was designed with a locking ring that
allows the screw to be locked and positioned obliquely. Due to the paucity of
biomechanical studies on this system, the present work aimed to evaluate the
influence of locked screw angulation on the resistance of the S.P.S. Free-Block
plate. METHODS: Forty synthetic bone cylinders with 10 mm fracture gap were used.
Forty seven-hole 3.5 mm stainless steel plates (two AO-like dynamic compression
holes and five locked holes) were assembled according to the orientation of the
locked screws: monocortical screws were positioned at 90o to the long axis of the
cylinder (Group 1), and monocortical screws were positioned at 70o to its
cylinder long axis (Group 2). In both groups, AO-like dynamic compression hole
screws were positioned bicortically and neutrally. For each group, six specimens
were tested until failure, three in bending and three in compression, to
determine the loads for fatigue testing. Subsequently, for each group, 14
specimens were tested for failure - seven by bending and seven in compression.
RESULTS: No significant failure differences were observed between Groups 1 and 2
under static-loading or fatigue test. CLINICAL SIGNIFICANCE: In a fracture gap
model the orientation of the locked monocortical screws did not show any
influence on the mechanical performance of the S.P.S. Free-Block to tests of
axial compression and four-point bending.
PMID- 23154448
TI - Poly(acrylic acid) modified lanthanide-doped GdVO4 hollow spheres for up
conversion cell imaging, MRI and pH-dependent drug release.
AB - In this study, multifunctional poly(acrylic acid) modified lanthanide-doped
GdVO(4) nanocomposites [PAA@GdVO(4): Ln(3+) (Ln = Yb/Er, Yb/Ho, Yb/Tm)] were
constructed by filling PAA hydrogel into GdVO(4) hollow spheres via photoinduced
polymerization. The up-conversion (UC) emission colors (green, red and blue) can
be tuned by changing the codopant compositions in the matrices. The composites
have potential applications as bio-probes for cell imaging. Meanwhile, the hybrid
spheres can act as T(1) contrast agents for magnetic resonance imaging (MRI)
owing to the existence of Gd(3+) ions on the surface of composites. Due to the
nature of PAA, DOX-loaded PAA@GdVO(4):Yb(3+)/Er(3+) system exhibits pH-dependent
drug releasing kinetics. A lower pH offers a faster drug release rate. Such
character makes the loaded DOX easily released at cancer cells. The cell uptake
process of drug-loaded composites was observed by using confocal laser scanning
microscopy (CLSM). The results indicate the potential application of the
multifunctional composites as theragnostics (effective bimodal imaging probes and
pH-responsive drug carriers).
PMID- 23154449
TI - Elevated levels of endothelial cell-derived microparticles following short-term
withdrawal of continuous positive airway pressure in patients with obstructive
sleep apnea: data from a randomized controlled trial.
AB - BACKGROUND: Obstructive sleep apnea has been associated with impaired endothelial
function; however, the mechanisms underlying this association are not completely
understood. Cell-derived microparticles may provide a link between obstructive
sleep apnea and endothelial dysfunction. OBJECTIVES: This randomized controlled
trial aimed to examine the effect of a 2-week withdrawal of continuous positive
airway pressure (CPAP) therapy on levels of circulating microparticles. METHODS:
Forty-one obstructive sleep apnea patients established on CPAP treatment were
randomized to either CPAP withdrawal (subtherapeutic CPAP) or continuing
therapeutic CPAP, for 2 weeks. Polysomnography was performed and circulating
levels of microparticles were analyzed by flow cytometry at baseline and 2 weeks.
RESULTS: CPAP withdrawal led to a recurrence of obstructive sleep apnea. Levels
of CD62E+ endothelium-derived microparticles increased significantly in the CPAP
withdrawal group compared to the continuing therapeutic CPAP group (median
difference in change +32.4 per ul; 95% CI +7.3 to +64.1 per ul, p = 0.010). CPAP
withdrawal was not associated with a statistically significant increase in
granulocyte, leukocyte, and platelet-derived microparticles when compared with
therapeutic CPAP. CONCLUSIONS: Short-term withdrawal of CPAP therapy leads to a
significant increase in endothelium-derived microparticles, suggesting that
microparticle formation may be causally linked to obstructive sleep apnea and may
promote endothelial activation.
PMID- 23154450
TI - Polypoid adenomas secondary to inflammatory colorectal polyps in 2 miniature
dachshunds.
AB - Two miniature dachshunds, a 7-year-old neutered male and an 8-year-old male,
presented with chronic hematochezia and tenesmus. A solitary pedunculated or
multiple diffuse colorectal polyps were identified by colonoscopy and resected by
polypectomy. Inflammatory colorectal polyps (ICRPs) were diagnosed according to
histopathological findings. Both cases were treated with immunosuppressive
therapy, and the clinical signs were resolved, although the colorectal polyps
remained to some extent. Several months after the initial diagnosis, both cases
presented with recurrence of hematochezia and enlargement of the polyps. A second
colonoscopic polypectomy was performed, and adenoma was diagnosed
histopathologically in both cases. ICRPs are a nonneoplastic disease, but their
long-term prognosis is unknown. Careful follow-up seems to be important, and
repetitive biopsy is recommended when growth of polyps is identified in miniature
dachshunds with ICRPs.
PMID- 23154451
TI - A case report of spontaneous polyarthritis in cynomolgus monkeys.
AB - Veterinary x-ray photography and examinations of synovial fluid, blood and urine
were conducted on a Cynomolgus Monkey from China (5 years old) which exhibited
macroscopically visible systemic joint swelling after the quarantine period. The
presence of inflammatory cells in the synovial fluid obtained by arthrocentesis,
high counts of neutrophils, monocytes and large unstained cells and the elevated
serum CRP level suggested that the lesions in this animal were due to
polyarthritis.
PMID- 23154452
TI - Hemato-biochemical responses to packing in donkeys administered ascorbic acid
during the harmattan season.
AB - Experiments were performed to investigate the effect of ascorbic acid (AA) in
reducing hemato-biochemical changes in pack donkeys during the cold-dry
(harmattan) season. Six experimental donkeys administered orally AA (200 mg/kg)
and six control donkeys not administered ascorbic acid were subjected to packing.
Blood samples were collected from all donkeys for hematological and biochemical
analyses. In the control donkeys, packed cell volume (PCV), erythrocyte count and
hemoglobin concentration (Hb) decreased significantly (P<0.05) at the end of
packing. In the experimental donkeys, there was no significant difference between
the pre- and post-packing values of PCV, erythrocyte count and Hb. In the control
donkeys, the neutrophil and neutrophil:lymphocyte ratio increased significantly
(P<0.05) post packing, but in the experimental donkeys, the pre- and post-packing
values were not significantly different. The eosinophil count increased
significantly (P<0.05) in experimental and control donkeys post packing. In
conclusion, packing exerted significant adverse effects on the hematological
parameters ameliorated by AA administration. AA may modulate neutrophilia and
induce a considerable alteration of erythroid markers in donkeys subjected to
packing during the harmattan season.
PMID- 23154453
TI - The critical point at which post-weaning individual housing conditions affect the
emission of 22-kHz calls in male rats.
AB - It is known that long-term post-weaning individual housing significantly reduces
emissions of 22-kHz calls in male rats. In this study, we assessed post-weaning
successive changes in 22-kHz calls emitted by male rats under two different types
of post-weaning housing conditions (individually and socially). In addition, we
evaluated the critical point at which a significant reduction in 22-kHz calls
could be observed in male rats housed individually after weaning. Significantly
fewer 22-kHz calls were emitted by individually housed rats compared to socially
housed rats at 16 weeks of age, indicating that 13 weeks after weaning may be a
critical point for the reduction of 22-kHz calls caused by post-weaning
individual housing.
PMID- 23154454
TI - Residual malignant and normal plasma cells shortly after high dose melphalan and
stem cell transplantation. Highlight of a putative therapeutic window in Multiple
Myeloma?
AB - Multiple Myeloma (MM) is an incurable malignant plasma cell disorder. We have
evaluated the counts of Multiple Myeloma Cells (MMCs) and normal plasma cells (N
PCs), seven days after high-dose melphalan (HDM) and autologous stem
transplantation (ASCT). Two third of patients had detectable minimal residual
disease (MRD+) (71.7 MMCs/uL) after induction treatment with dexamethasone and
proteasome inhibitor. MMC counts were reduced by 92% (P <= .05) but not
eradicated 7 days after HDM+ASCT. Post-HDM+ASCT MMCs were viable and bathed in a
burst of MMC growth factors, linked with post-HDM aplasia. In one third of
patients (MRD- patients), MMCs were not detectable after induction treatment and
remained undetectable after HDM+ASCT. Major difference between MRD- and MRD+
patients is that N-PC counts were increased 3 fold (P<.05) by HDM+ASCT in MRD-
patients, but were unaffected in MRD+ patients. Possible explanation could be
that clearance of MMCs in MRD- patients makes more niches available for N-PCs.
Thus, MMCs are not fully eradicated shortly after HDM, are bathed in high
concentrations of MMC growth factors in an almost desert BM, are viable in short
term culture, which suggests providing additional therapies shortly after HDM to
kill resistant MMCs before full repair of lesions.
PMID- 23154455
TI - Increased pulsatility index is associated with intracranial arterial
calcification.
AB - BACKGROUND/AIMS: An increase in the pulsatility index (PI) has been suggested to
reflect distal vascular resistance. The purpose of the present study was to
investigate the association between intracranial arterial calcification and
intracranial PIs. METHODS: Consecutive patients with acute ischemic stroke or
transient ischemic attack were included. The PIs of both middle cerebral arteries
(MCAs) were measured by transcranial Doppler ultrasonography. Intracranial
carotid artery calcification (ICAC) was assessed on computed tomography
angiography, and then compared with the mean PI of both MCAs. Patients with
internal carotid artery steno-occlusion were excluded from this study. RESULTS: A
total of 156 patients were finally enrolled. The prevalence of diabetes increased
as the PI value increased (p for trends; p = 0.025). PI was correlated with ICAC
score (r = 0.413, p < 0.001) and age (r = 0.507, p < 0.001). Multiple linear
regression analysis indicated that aging and ICAC were independent determinants
of the PI of MCA after adjusting for sex, systolic blood pressure, smoking, and
the presence of diabetes. CONCLUSIONS: This study shows that an increase in PI
was correlated with the severity of ICAC, which suggests calcification-related
vascular resistance might have a role in the elevation of PI.
PMID- 23154456
TI - A novel distribution of visual field test points to improve the correlation
between structure-function measurements.
AB - PURPOSE: To create a new visual field (VF) test grid centered at the optic disc
(disc-centered field [DCF]) and to infer the combination of VF test points
(structure-function field [SFF]), taken from the DCF and the conventional fovea
centered 24-2 grid (24-2) of standard automated perimetry, which yields the
strongest sectorial correlation between structure-function measurements of
retinal nerve fiber layer (RNFL) thickness and VF sensitivity. METHODS: In 50
eyes with ocular hypertension or open angle glaucoma, the DCF and 24-2 VF were
measured with a humphrey field analyzer II (Full Threshold strategy) and RNFL
thickness was measured with Stratus optical coherence tomography. test points
from the DCF and 24-2 VF Were combined and divided into 12 sectors according to
the spatial distribution of the RNFL. A novel VF for structure-function studies
was established using the following criteria: each sector must contain at least
one or two test points (depending on the sector's location), and the combination
of test points which yields the strongest structure-function correlation is
selected. RESULTS: The SFF consisted of 40 test points. The structure-function
correlation for the SFF was compared with the standard 24-2 VF; a multiple
comparison test for dependent groups was carried out using a percentile bootstrap
method, which indicated that the sector correlation coefficients in the SFF were
significantly higher than those in the 24-2 VF. CONCLUSIONS: The SFF, with fewer
test locations, has a stronger structure-function correlation than the 24-2 VF.
This improved correlation may help clinicians to better interpret functional
measurements in relation to structural measurements.
PMID- 23154457
TI - Wnt signaling promotes Muller cell proliferation and survival after injury.
AB - PURPOSE: Muller glia respond to retinal injury by a reactive gliosis, but only
rarely do mammalian glial cells re-enter the cell cycle and generate new neurons.
In the nonmammalian retina, however, Muller glia act as stem/progenitor cells.
Here, we tested the function of Wnt signaling in the postinjury retina, focusing
on its ability to influence mammalian Muller cell dedifferentiation,
proliferation, and neurogenesis. METHODS: A 532 nm frequency doubled neodymium
doped yttrium aluminum garnet (ND:YAG) laser was used to create light burns on
the retina of Axin2(LacZ/+) Wnt reporter mice. At various time points after
injury, retinas were analyzed for evidence of Wnt signaling as well as glial cell
response, proliferation, and apoptosis. Laser injuries also were created in
Axin2(LacZ/LacZ) mice, and the effect of potentiated Wnt signaling on retinal
repair was assessed. RESULTS: A subpopulation of mammalian Muller cells are Wnt
responsive and, when Wnt signaling is increased, these cells showed enhanced
proliferation in response to injury. In an environment of heightened Wnt
signaling, caused by the loss of the Wnt negative regulator Axin2, Muller cells
proliferated after injury and adopted the expression patterns of retinal
progenitor cells (RPCs). The Wnt-responsive Muller cells also exhibited long-term
survival and, in some cases, expressed the rod photoreceptor marker, rhodopsin.
CONCLUSIONS: The Wnt pathway is activated by retinal injury, and prolonging the
endogenous Wnt signal causes a subset of Muller cells to proliferate and
dedifferentiate into RPCs. These data raised the possibility that transient
amplification of Wnt signaling after retinal damage may unlock the latent
regenerative capacity long speculated to reside in mammalian neural tissues.
PMID- 23154458
TI - Capsaicin-induced corneal sensory denervation and healing impairment are reversed
by NGF treatment.
AB - PURPOSE: We aimed to evaluate the nerve growth factor (NGF) pathway and its
influence on corneal healing mechanisms in normal conditions and in an animal
model of corneal denervation induced by capsaicin. METHODS: Peripheral sensory
damage was induced in rat pups by subcutaneous injection of capsaicin and the
effects evaluated by hot-plate test, corneal nerve count, and tear secretion.
Corneal damage was induced in capsaicin-treated and -untreated rats by epithelial
scraping. Healing rate; NGF pathway (NGF, tyrosine kinase A [TrkA], p75); and the
stem cell marker p63 were evaluated by RT-PCR, ELISA, Western blot, and
immunohistochemistry. The effects of exogenous NGF administration as eye drop
formulation were also tested. RESULTS: Capsaicin treatment induced a significant
reduction of peripheral sensitivity, corneal innervation, tear secretion, and
corneal healing rate. The ocular effects of capsaicin treatment were associated
with an NGF pathway alteration. NGF eye drop treatment aided corneal healing
mechanisms through a significant increase in the NGF receptors TrkA and p75, and
in the stem cell marker p63. CONCLUSIONS: In this study, we show that an
alteration in the NGF pathway is responsible for a delay in corneal healing in an
animal model of sensory denervation. Moreover, we show that NGF eye drop
administration modulates corneal innervation, epithelial cell healing, and
corneal stem cells. These findings may trigger further research on the role of
the NGF pathway in limbal stem cell deficiency.
PMID- 23154459
TI - Comparative regional pupillography as a noninvasive biosensor screening method
for diabetic retinopathy.
AB - PURPOSE: We describe infrared regional pupillometry as an objective comparative
assessment of midperipheral to central retinal sensitivity and to correlate with
midperipheral retinal ischemia in diabetic subjects. METHODS: We tested 12 normal
and 17 diabetic subjects using bilateral infrared pupillometry. The diabetic
cohort included seven subjects without, five with mild, three with moderate, and
two with severe non-proliferative diabetic retinopathy (NPDR). Central and
annular stimuli of varying intensity were presented to one eye, and pupillary
amplitude and constriction velocity were measured from both eyes. Light stimulus
of increasing intensity was presented as 20 consecutive trials (stimulus duration
of 300 ms with 3000 ms intervals). The ratio of central to peripheral responses
(Q values) was calculated for each stimulus configuration. Average responses with
respect to the stimulus strength were regressed with Gompertz sigmoid function.
RESULTS: Control and moderate/severe NPDR cases comparison showed statistically
significant differences in amplitude (Q(A)) and constriction velocity (Q(CV))
(Wilcoxon rank sum test P = 0.002, respectively). Age difference for these groups
was not statistically significant (Wilcoxon rank sum test P = 0.15). The
comparison of control and diabetic subjects without NPDR/mild NPDR was
statistically significant for Q(A) and Q(CV) (Wilcoxon rank sum test P = 0.0002
and P = 0.001, respectively). Q(A) and Q(CV) differences were statistically
significant between moderate/severe NPDR cases and subjects without or mild NPDR
cases (Wilcoxon rank sum test P = 0.013). CONCLUSIONS: Q(A) and Q(CV) values
correlated highly with the severity of diabetic retinopathy, but not with the
duration of diabetes.
PMID- 23154460
TI - Forskolin modifies retinal vascular development in Mrp4-knockout mice.
AB - PURPOSE: Multidrug resistance protein 4 (MRP4) effluxes a wide variety of
endogenous compounds, including cyclic adenosine monophosphate (cAMP), and is
exclusively expressed in vascular endothelial cells (ECs) of the retina. This
study aimed to investigate the role of MRP4 in retinal vascular development.
METHODS: The retinal vascular phenotype of Mrp4(-/-) mice was examined by whole
mount immunohistochemistry at P3, P6, and P14. The retinas from P6 pups that
received an intraperitoneal injection of either solvent control or forskolin, an
inducer of intracellular cAMP formation, at P4 and P5 were analyzed in terms of
their vascular formation (vascular length, vascular branching, vascular density,
and the number of tip cells), cell proliferation and apoptosis, and vessel
stability. RESULTS: The Mrp4(-/-) mice exhibited no overt abnormalities in the
development of the retinal vasculature, but retinal vascular development in the
Mrp4(-/-) mice was suppressed in response to forskolin administration. There was
a significant decrease in the vascular length, vascular branching, and vascular
density, and inhibited tip cell formation at the vascular front. The forskolin
treated Mrp4(-/-) mice showed an increased number of Ki67-positive and cleaved
caspase 3-positive ECs, a significant decrease in the amount of pericyte
coverage, and a reduced number of empty sleeves. In pups exposed to hyperoxia
(75% oxygen) from P7 to P12, the Mrp4(-/-) mice showed a significant increase in
the unvascularized retinal area. CONCLUSIONS: Mrp4(-/-) mice exhibited suppressed
retinal vascular development in response to forskolin treatment. Thus, Mrp4 might
have protective roles in retinal vascular development by regulating the
intracellular cAMP level.
PMID- 23154461
TI - Progressive degeneration of the retinal nerve fiber layer in patients with
multiple sclerosis.
AB - PURPOSE: To quantify changes in the retinal nerve fiber layer (RNFL) of patients
with multiple sclerosis (MS) over 3 years and to evaluate whether treatment
protects against RNFL degeneration. METHODS: Ninety-four MS patients and 50
healthy subjects were followed-up over 3 years. All subjects underwent a complete
ophthalmic examination, which included assessment of visual acuity (Snellen
chart), color vision (Ishihara pseudoisochromatic plates), visual field
examination, optical coherence tomography (OCT), and visual evoked potentials
(VEPs). All patients were reevaluated at 12, 24, and 36 months to quantify
changes in the RNFL. RESULTS: Changes were detected in RNFL thickness at the 36
month follow-up. Significant decreases (P < 0.05, t-test) were observed in the
mean, superior, inferior, and temporal RNFL thicknesses, and macular volume
provided by OCT, and in the P100 latency of VEP of the MS group, but only in the
mean and inferior RNFL thicknesses of the healthy control group. Greater changes
in the superior and inferior RNFL thicknesses during follow-up were detected in
the MS group. Differences between treatments were not detected, but untreated
patients had higher degeneration in the mean and superior RNFL thicknesses during
the follow-up (P = 0.040 and P = 0.19, respectively). CONCLUSIONS: Progressive
axonal loss can be detected in the optic nerve fiber layer of MS patients.
Analysis of the RNFL by OCT can be useful for evaluating MS progression and
efficacy of treatment as a neuroprotective factor against axonal degeneration.
PMID- 23154462
TI - Optimizing the information yield of 3-D OCT in glaucoma.
AB - PURPOSE: To determine, first, which regions of 3-D optical coherence tomography
(OCT) volumes can be segmented completely in the majority of subjects and,
second, the relationship between analyzed area and thickness measurement test
retest variability. METHODS: Three-dimensional OCT volumes (6 * 6 mm) centered
around the fovea and optic nerve head (ONH) of 925 Rotterdam Study participants
were analyzed; 44 participants were scanned twice. Volumes were segmented into 10
layers, and we determined the area where all layers could be identified in at
least 95% (macula) or 90% (ONH) of subjects. Macular volumes were divided in 2 *
2, 4 * 4, 6 * 6, 8 * 8, or 68 blocks. We placed two circles around the ONH; the
ONH had to fit into the smaller circle, and the larger circle had to fit into the
segmentable part of the volume. The area between the circles was divided in 3 to
12 segments. We determined the test-retest variability (coefficient of
repeatability) of the retinal nerve fiber layer (RNFL) and ganglion cell layer
(RGCL) thickness measurements as a function of size of blocks/segments. RESULTS:
Eighty-two percent of the macular volume could be segmented in at least 95% of
subjects; for the ONH, this was 65% in at least 90%. The radii of the circles
were 1.03 and 1.84 mm. Depending on the analyzed area, median test-retest
variability ranged from 8% to 15% for macular RNFL, 11% to 22% for macular RGCL,
5% to 11% for the two together, and 18% to 22% for ONH RNFL. CONCLUSIONS: Test
retest variability hampers a detailed analysis of 3-D OCT data. Combined macular
RNFL and RGCL thickness averaged over larger areas had the best test-retest
variability.
PMID- 23154463
TI - Coenzyme Q10 instilled as eye drops on the cornea reaches the retina and protects
retinal layers from apoptosis in a mouse model of kainate-induced retinal damage.
AB - PURPOSE: To evaluate if coenzyme Q10 (CoQ10) can protect retinal ganglion cells
(RGCs) from apoptosis and, when instilled as eye drops on the cornea, if it can
reach the retina and exert its antiapoptotic activity in this area in a mouse
model of kainate (KA)-induced retinal damage. METHODS: Rat primary or cultured
RGCs were subjected to glutamate (50 MUM) or chemical hypoxia (Antimycin A, 200
MUM) or serum withdrawal (FBS, 0.5%) in the presence or absence of CoQ10 (10
MUM). Cell viability was evaluated by light microscopy and fluorescence-activated
cell sorting analyses. Apoptosis was evaluated by caspase 3/7 activity and
mitochondrion depolarization tetramethylrhodamine ethyl ester analysis. CoQ10
transfer to the retina following its instillation as eye drops on the cornea was
quantified by HPLC. Retinal protection by CoQ10 (10 MUM) eye drops instilled on
the cornea was then evaluated in a mouse model of KA-induced excitotoxic retinal
cell apoptosis by cleaved caspase 3 immunohistofluorescence, caspase 3/7 activity
assays, and quantification of inhibition of RGC loss. RESULTS: CoQ10
significantly increased viable cells by preventing RGC apoptosis. Furthermore,
when topically applied as eye drops to the cornea, it reached the retina, thus
substantially increasing local CoQ10 concentration and protecting retinal layers
from apoptosis. CONCLUSIONS: The ability of CoQ10 eye drops to protect retinal
cells from apoptosis in the mouse model of KA-induced retinal damage suggests
that topical CoQ10 may be evaluated in designing therapies for treating apoptosis
driven retinopathies.
PMID- 23154464
TI - Transgenic or not? No simple answer! New biotechnology-based plant breeding
techniques and the regulatory landscape.
PMID- 23154465
TI - Repair or regenerate--how can we tip the balance?
AB - The fourth EMBO conference on 'The Molecular and Cellular Basis of Regeneration
and Repair', held in September 2012, brought together researchers from both the
regeneration and wound-healing fields. The meeting spanned a wide range of
research topics from basic science to clinical application, and a veritable
melting pot of model organisms and approaches resulted in an excellent fourth
conference in this series.
PMID- 23154466
TI - Nicotinamide mononucleotide adenylyltransferase maintains active zone structure
by stabilizing Bruchpilot.
AB - Active zones are specialized presynaptic structures critical for
neurotransmission. We show that a neuronal maintenance factor, nicotinamide
mononucleotide adenylyltransferase (NMNAT), is required for maintaining active
zone structural integrity in Drosophila by interacting with the active zone
protein, Bruchpilot (BRP), and shielding it from activity-induced ubiquitin
proteasome-mediated degradation. NMNAT localizes to the peri-active zone and
interacts biochemically with BRP in an activity-dependent manner. Loss of NMNAT
results in ubiquitination, mislocalization and aggregation of BRP, and subsequent
active zone degeneration. We propose that, as a neuronal maintenance factor,
NMNAT specifically maintains active zone structure by direct protein-protein
interaction.
PMID- 23154467
TI - Silencing of proviruses in embryonic cells: efficiency, stability and chromatin
modifications.
AB - Embryonic stem cells repress retroviral infection through transcriptional
silencing of proviral DNAs. We characterized two distinct mechanisms of silencing
in embryonic mouse cells infected by Moloney murine leukaemia virus (MLV): a
highly efficient one targeting the proline transfer RNA primer-binding site
(PBSpro), and a less efficient one operating independently of the PBS. Rare virus
expressing populations were isolated, and the timing and efficiency of
establishment of silencing were determined. Superinfection of the selected virus
expressing cells with a second virus carrying a distinguishable reporter revealed
that the PBSpro-directed silencing was still largely intact, whereas the PBS
independent silencing was partially reduced. The timing and stability of
silencing, and the associated chromatin modifications on newly established and
endogenous proviruses were determined. The results indicate that epigenetic
mechanisms with different specificity and efficiency are used to silence the
exogenous retroviral sequences in embryonic cells.
PMID- 23154468
TI - Production of phosphatidylinositol 5-phosphate via PIKfyve and MTMR3 regulates
cell migration.
AB - Although phosphatidylinositol 5-phosphate (PtdIns5P) is present in many cell
types and its biogenesis is increased by diverse stimuli, its precise cellular
function remains elusive. Here we show that PtdIns5P levels increase when cells
are stimulated to move and we find PtdIns5P to promote cell migration in tissue
culture and in a Drosophila in vivo model. First, class III phosphatidylinositol
3-kinase, which produces PtdIns3P, was shown to be involved in migration of
fibroblasts. In a cell migration screen for proteins containing PtdIns3P-binding
motifs, we identified the phosphoinositide 5-kinase PIKfyve and the
phosphoinositide 3-phosphatase MTMR3, which together constitute a
phosphoinositide loop that produces PtdIns5P via PtdIns(3,5)P(2). The ability of
PtdIns5P to stimulate cell migration was demonstrated directly with exogenous
PtdIns5P and a PtdIns5P-producing bacterial enzyme. Thus, the identified
phosphoinositide loop defines a new role for PtdIns5P in cell migration.
PMID- 23154469
TI - Ocular surface temperature gradient is increased in eyes with bacterial corneal
ulcers.
AB - AIMS: To investigate the ocular surface temperature gradient in eyes with
bacterial corneal ulcers. METHODS: Prospective examination of 12 eyes with
bacterial corneal ulcers (group 1) and 12 control eyes (group 2). Infrared
thermal imaging (Tomey TG 1000) was used to study the temperature of the ocular
surface. The mean, minimum and maximum temperature of the ocular surface and
temperature course over a time period of 10 s of sustained eye opening were
evaluated. Furthermore, a correlation between the overall corneal temperature and
the temperature at the base of the corneal ulcers was determined. RESULTS: A
significant difference between both groups was present. Mean corneal temperature
was 35.6 degrees C +/- 0.9 in group 1 and 34.8 degrees C +/- 0.8 in group 2 (p =
0.033). The temperature course over 10 s of sustained eye opening was -0.6
degrees C +/- 0.4 in group 1 and -0.3 degrees C +/- 0.2 in group 2 (p = 0.045).
There was a close correlation between the mean temperature at the base of the
corneal ulcer and the overall corneal temperature (r = 0.92, p < 0.001).
CONCLUSION: Infrared thermal imaging can be used to objectively determine the
increased ocular surface temperature in patients with bacterial corneal ulcers.
The use of dynamic thermography may offer new options to monitor ocular surface
alterations.
PMID- 23154471
TI - Increased adenosine A1 receptor levels in hemianopia patients after cerebral
injury: an application of PET using 11C-8-dicyclopropylmethyl-1-methyl-3
propylxanthine.
AB - PURPOSE: The aim of this study was to apply positron emission tomography (PET)
with C-8-dicyclopropylmethyl-1-methyl-3-propylxanthine (MPDX), a radioligand for
adenosine A1 receptor (A1R), to patients with hemianopia caused by brain injury
to study neurorepair mechanisms in the brain. PATIENTS AND METHODS: Four patients
with homonymous hemianopia and 15 healthy subjects were examined using PET to
measure cerebral glucose metabolism, C-flumazenil (FMZ) binding to the central
benzodiazepine receptor, and MPDX binding to A1R. Left and right regions of
interest (ROIs) were selected, and semiquantitative data on the 3 kinds of PET
examinations were obtained. The ROIs were referenced using the data for
homologous regions in the contralateral hemisphere [ipsilateral/contralateral
(I/C) ratio]. RESULTS: The I/C ratios for cerebral glucose metabolism and FMZ
binding were low in the primary visual cortex (PVC) and visual association cortex
in all the patients, whereas MPDX binding increased in the PVC in patients 1 and
2. Patients 1 and 2 experienced improvement in their visual field after 1 year.
However, the other 2 patients showed no changes. We observed an increase in MPDX
binding to A1R in the injured portion of the PVC in the patients who recovered.
CONCLUSIONS: Evaluation of A1R by MPDX-PET may be useful for predicting prognosis
and understanding the compensatory and reorganization processes in hemianopia
caused by organic brain damage.
PMID- 23154470
TI - (18)F-FDG PET in the evaluation of acuity of deep vein thrombosis.
AB - PURPOSE: F-FDG PET has been used for vascular disease, but its role in deep vein
thrombosis (DVT) remains prospectively unexplored. PATIENTS AND METHODS: Whole
body F-FDG PET/CT scans were performed in patients 1 to 10 weeks after onset of
symptomatic DVT (n = 12) and in control subjects without DVT (n = 24). The
metabolic activity (SUVmax) of thrombosed and contralateral nonthrombosed vein
segments was determined. The sensitivity and specificity of F-FDG PET/CT for the
diagnosis of DVT were determined by receiver operating characteristic curve
analyses. In 2 patients with DVT, changes in the metabolic activity of thrombosed
vein segments in serial F-FDG PET scans. RESULTS: The metabolic activity in
thrombosed veins [SUVmax, 2.41 (0.75)] was visually appreciable and significantly
higher than in nonthrombosed veins in either the contralateral extremity of
patients with DVT [SUVmax, 1.09 (0.25), P = 0.007] or control subjects [1.21
(0.22), P < 0.001]. The area under the receiver operating characteristic curve
for SUVmax was 0.9773 (P < 0.001), indicating excellent accuracy. An SUVmax
threshold of greater than 1.645 was 87.5% sensitive and 100% specific for DVT.
Metabolic activity in thrombosed veins correlated significantly with time from
DVT symptom onset (decrease in SUVmax of 0.02/d, P < 0.05). Best-fit-line
analyses suggested that approximately 84 to 91 days after acute DVT, the maximum
metabolic activity of thrombosed veins would return to normal levels.
CONCLUSIONS: F-FDG PET/CT is accurate for detecting acute symptomatic, proximal
DVT. Metabolic activity in thrombosed veins decreases with time, suggesting that
F-FDG PET may be helpful in assessing the age of the clot.
PMID- 23154472
TI - (18)F-FDG PET-detected synchronous primary neoplasms in the staging of esophageal
cancer: incidence, cost, and impact on management.
AB - PURPOSE: F-Fluorodeoxyglucose positron emission tomography (F-FDG PET) imaging is
increasingly the standard of care in the staging of esophageal cancer.
Synchronous neoplasms may be identified, and this study evaluated the prevalence
of such tumors and their impact on management. METHODS: Five hundred ninety-one
(73.6%) of 803 consecutive patients with biopsy-proven esophageal cancer
underwent staging F-FDG PET or PET/CT scans. F-FDG-avid lesions were considered
synchronous primary neoplasms if occurring at locations atypical for metastases
from the known primary, a marked discordance in the F-FDG avidity from that of
the primary tumor, and if there was no prior detection on conventional imaging.
Additional investigations as appropriate were undertaken, and histopathological
verification was obtained where possible to validate the suspected synchronous
neoplasm. RESULTS: A synchronous neoplasm was suspected in 55 (9.3%) of 591
patients, predominantly at sites in the colon (26) and head and neck (21).
Additional investigations in 43 cases revealed malignant neoplasms in 8 (18.6%),
premalignant in 9 (20.9%), and benign lesions in 26 (60.5%) cases. The management
plan was altered in 8 patients, 1.4% overall. The total cost of added tests was
$27,482.57 (&OV0556;21,024) with the decision to treat the esophageal cancer
deferred by a mean of 10.7 days. CONCLUSION: F-FDG uptake concerning for
synchronous neoplasms is evident in approximately 1 in 10 cases, and of these a
minority will represent a malignant neoplasm that significantly impacts on
treatment. The overall added costs per patient are relatively modest and the
treatment delay within acceptable limits of clinical practice.
PMID- 23154473
TI - Human radiation dose estimation of (11)C-CFT using whole-body PET.
AB - PURPOSE: C-Labeled 2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane (C-CFT) is
a commonly used positron emission tomography (PET) tracer for dopamine
transporters imaging. The present study estimated human radiation absorbed doses
of C-CFT based on whole-body PET imaging in healthy subjects. METHODS: Whole-body
PET was performed on 6 subjects after injection of 472.06 +/- 116.47 MBq of C
CFT. 7 Frames were acquired for about 70 min in 7 segments of the body. Regions
of interest were drawn on PET images of source organs. Residence time was
calculated as the area under the time-activity curve. Radiation dosimetry was
calculated from organ residence time using the medical internal radiation
dosimetry (MIDR) method. RESULTS: The organs with the highest radiation-absorbed
doses were the urinary bladder, followed the spleen, pancreas, kidneys, and
stomach. The dose-limiting critical organ was the urinary bladder. The effective
dose was 8.89E-03 mSv/MBq (22.9 mrem/mCi). Biexponential fitting of mean bladder
activity demonstrated that 18% of activity was excreted via the urine.
CONCLUSIONS: The potential radiation risks of C-CFT associated with in this study
are well within accepted limits. C-CFT demonstrates a favorable radiation dose
profile in humans and allows multiple PET examinations on the same subject per
year.
PMID- 23154474
TI - Comparison of (99m)Tc-MIBI SPECT/18F-FDG PET imaging and cardiac magnetic
resonance imaging in patients with idiopathic dilated cardiomyopathy: assessment
of cardiac function and myocardial injury.
AB - OBJECTIVE: The aim of this study is to evaluate the agreement between myocardial
F-FDG PET imaging and cardiac magnetic resonance imaging (cMRI) in assessing
cardiac function and relationship of cMRI late gadolinium enhancement (cMRI-LGE)
and myocardial perfusion/metabolism pattern in patients with idiopathic dilated
cardiomyopathy (IDCM). METHODS: Forty-two consecutive patients diagnosed with
IDCM were enrolled. All patients underwent Tc-MIBI SPECT, gated F-FDG PET
imaging, and cMRI within 3-7 days. Cardiac function parameters were calculated
using PET and cMRI. The segments analysis was performed using a 17-segment model.
Patterns of perfusion/metabolism were classified as normal, mismatch, mild-to
moderate match, and severe match, and cMRI-LGE was classified into 3 categories
(non-LGE, mid-wall LGE, and transmural LGE). RESULTS: The correlation between
gated PET and cMRI was excellent for end-diastolic volume (EDV; r = 0.948, P <
0.001), end-systolic volume (ESV; r = 0.939, P < 0.001), and left ventricular
ejection fraction (LVEF; r = 0.685, P < 0.001). EDV and ESV were underestimated,
whereas LVEF was slightly overestimated by gated PET in comparison to cMRI.
Perfusion/metabolism patterns varied in 3 different categories of non-LGE, mid
wall LGE, and transmural LGE (chi = 14.276, P < 0.001). Also, 71.0% (44/62)
segments with mid-wall LGE had normal perfusion/metabolism patterns, and 75.9%
(63/83) perfusion/metabolism mismatch segments were shown as non-LGE. The
incidence of LGE was significantly higher in segments with severe match than the
other 3 segment groups (chi = 112.53, P < 0.001). CONCLUSION: There is an
excellent agreement between gated PET and cMRI in assessment of cardiac function.
LGE-cMRI is much more sensitive in detecting moderate fibrosis, while PET could
detect more impaired but viable myocardium. Combining the 2 imaging modalities is
useful for providing more comprehensive evaluations of myocardial injury in
patients with IDCM.
PMID- 23154475
TI - Potential role of FDG PET/CT imaging for assessing venous thromboembolic
disorders.
PMID- 23154476
TI - Tips for giving a memorable presentation, part VI: the effective use of questions
by a speaker, and answering questions from listeners.
AB - Previous articles in this series have focused on tips for educators and leaders
in giving a presentation, followed by articles on composing the talk and
PowerPoint slides. This article focuses on how a speaker can effectively use
questions to engage the audience and answer questions from the listeners,
including members of the media. Additional comments will be given on how to give
a clear presentation so that many questions will not be necessary.
PMID- 23154477
TI - Serendipitous observation of hepatic metastases on (18)F-fluoride PET in a
patient with infiltrating ductal carcinoma of breast: correlation with contrast
enhanced CT.
AB - Serendipitous observation of multifocal bilobar hepatic metastases on F-fluoride
(NaF) PET arising in the setting of infiltrating ductal carcinoma of breast is
described in the present report. A 46-year-old female patient with infiltrating
ductal carcinoma had an F-fluoride PET which demonstrated uptake in multiple
skeletal metastasis and several upper abdominal lesions corresponding to liver
metastases on contrast enhanced CT. F-NaF uptake in soft tissue metastases are
likely to be more frequently encountered with the increasing use of F-NaF PET/CT
in oncology.
PMID- 23154478
TI - Presurgical lateralization of seizure focus in temporal lobe epilepsy with
noninvasive imaging.
AB - We retrospectively compared the seizure focus-localizing capability of interictal
PET/CT to that of interictal magnetic resonance diffusion-weighted imaging and
ictal SPECT in 21 patient candidate for neurosurgery with temporal lobe epilepsy
(TLE) by assessing overall lateralizing ability of these modalities and
concordance of findings on these studies with results of electroencephalography
(EEG). PET/CT demonstrated the greatest lateralizing ability of any of the
imaging modalities and had the highest concordance rate for lateralization with
EEG, highlighting its increasing diagnostic utility in the preoperative imaging
workup of patients with medically intractable TLE.
PMID- 23154479
TI - Cardiac (18)F-FDG PET/CT with heparin detects infective vegetation in a patient
with mechanical valve replacement.
AB - We report the usefulness of F-FDG PET/CT for the detection and therapy evaluation
of the infective vegetation. A 64-year-old man with history of aortic valve
replacement presented with 2 months of fever without identifiable cause.
Echocardiogram showed no inflammation vegetation or abnormality of mechanical
valve function. FDG PET/CT with 50 IU/kg IV heparin revealed focal uptakes near
the mechanical aortic valve. After antibiotics therapy, fever was ameliorated,
and FDG PET/CT findings showed markedly decreased uptake of the lesions. FDG
PET/CT is a powerful tool to detect endocarditis even in patients with no
anatomical abnormalities.
PMID- 23154480
TI - Combined (11)C-methionine and 18F-FDG PET imaging in a case of cerebral
sparganosis.
AB - A 35-year-old man presented with right lower extremity numbness and weakness. CT
demonstrated an irregular left parietal hypoattenuation with a punctuate
calcification. MRI revealed a T1 low signal and T2 high signal lesion with
extensive surrounding edema. Gadolinium-enhanced MRI showed an irregular
enhancing lesion. F-FDG and C-methionine PET both demonstrated high uptake in the
left parietal lesion. Lesion SUV was 7.5 for F-FDG and 3.0 for C-methionine.
Surgical pathology demonstrated cerebral sparganosis.
PMID- 23154481
TI - "Hot" vertebra on (18)F-FDG PET scan: a case of vertebral hemangioma.
AB - An F-FDG-PET with CT scan was performed to stage a tongue cancer, revealing the
hypermetabolic region in the thoracic vertebra. This corresponded to a benign
lesion seen on MRIs and CT.Although these findings suggested a vertebral
hemangioma, "hot" vertebra in FDG-PET was atypical. The final diagnosis was
confirmed capillary hemangioma by the scopic biopsy and this lesion was no change
at 1 year later.Careful interpretation of metabolic (FDG-PET) and anatomic (CT
and MRI) images should be performed to accurately characterize the foci of
increased FDG uptake.
PMID- 23154484
TI - Soft cutting of single-wall carbon nanotubes by low temperature ultrasonication
in a mixture of sulfuric and nitric acids.
AB - To decrease single-wall carbon nanotube (SWCNT) lengths to a value of 100-200 nm,
aggressive cutting methods, accompanied by a high loss of starting material, are
frequently used. We propose a cutting approach based on low temperature intensive
ultrasonication in a mixture of sulfuric and nitric acids. The method is
nondestructive with a yield close to 100%. It was applied to cut nanotubes
produced in three different ways: gas-phase catalysis, chemical vapor deposition,
and electric-arc-discharge methods. Raman and Fourier transform infrared
spectroscopy were used to demonstrate that the cut carbon nanotubes have a low
extent of sidewall degradation and their electronic properties are close to those
of the untreated tubes. It was proposed to use the spectral position of the far
infrared absorption peak as a simple criterion for the estimation of SWCNT length
distribution in the samples.
PMID- 23154483
TI - Levels of serum ceruloplasmin associate with pediatric nonalcoholic fatty liver
disease.
AB - OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) in adolescents and children
is rapidly becoming one of the most common causes of chronic liver disease
worldwide. NAFLD varies from simple fatty liver to nonalcoholic steatohepatitis
(NASH) with possible fibrosis. Several studies suggest that oxidative stress
plays a central role in several metabolic abnormalities and cellular damage that
characterize NAFLD. We investigated whether transition metals and their related
proteins were related to NAFLD symptoms and their underlying processes. METHODS:
We measured copper, iron, ceruloplasmin (Cp) concentration and activity,
transferrin (Tf), ferroxidase activity, and ferritin, and we calculated Tf
saturation and Cp to Tf ratio (Cp/Tf) as an index of the activity of the
antioxidant Cp-Tf system in 100 children with biopsy-proven NAFLD. Pediatric
patients were grouped by nonalcoholic fatty liver disease score (NAS) >= 5 (30
subjects) and NAS < 5 (70). RESULTS: Cp distinguished children with NAS >= 5 from
those with NAS < 5 with an accuracy of 82%. Specifically, a receiver operator
characteristics curve showed that a cutoff of 28.6 mg/dL separated NAS >= 5 from
NAS < 5 with a specificity of 92% and a sensitivity of 76%. The Cp/Tf ratio, as
well as copper concentration and Cp activity, decreased in the NAS >= 5 group,
pointing out an imbalance in metal regulation. Either copper or Cp concentrations
were lower in subjects having ballooning. CONCLUSIONS: Serum antioxidant capacity
owing to Cp failure is strongly associated with NAFLD-related damage. Further
studies are, however, required to clarify the role of Cp in NAFLD pathogenesis
and to evaluate its potential application as diagnostic marker.
PMID- 23154485
TI - Does the real ReN2 have the MoS2 structure?
AB - Rhenium nitride (ReN(2)) with the hexagonal MoS(2) structure was recently
synthesized by metathesis reaction under high pressure. Here the calculated
elastic and thermodynamic stabilities and chemical bonding show that the MoS(2)
phase is unstable based on first-principles calculations. Meanwhile, the MoS(2)
type ReN(2) compound may be stabilized by nitrogen-vacancies from X-ray
diffraction and supercell calculations. Structure searches identify a monoclinic
C2/m phase for ReN(2), which is energetically more stable than previous
predictions and MoS(2) structure over a wide range of pressures. Above 130 GPa, a
tetragonal P4/mbm phase becomes favorable from enthalpy calculations. Both phases
have superior mechanical properties, and their syntheses would have important
applications fundamentally and technologically.
PMID- 23154486
TI - Synovial osteochondromatosis and sclerosing osteosarcoma in a cat.
AB - The clinical, radiographic and histological features of synovial
osteochondromatosis in multiple joints and an unrelated sclerosing osteosarcoma
of the left tibia in a cat are reported. Radiographic evaluation showed signs of
several nodular radiopacities in both stifles and both shoulders. Pathologic
transverse fractures of the left tibia and fibula were also present. A midfemoral
amputation of the left hindlimb was performed and treatment consisted of lifelong
administration of nonsteroidal anti-inflammatory drugs. Histological evaluation
confirmed synovial osteochondromatosis of the left stifle and sclerosing
osteosarcoma of the left tibia. This is the first report of a feline patient with
bilateral synovial osteochondromatosis that describes the clinical, radiographic
and histological aspects of this disease.
PMID- 23154487
TI - Total syntheses of pamamycin 607 and methyl nonactate: stereoselective
cyclisation of homoallylic alcohols that had been prepared with remote
stereocontrol using allylstannanes.
AB - The tin(IV) chloride mediated cyclisation of (Z)-homoallylic alcohols using
phenylselenenyl chloride or phthalimide in the presence of a Lewis acid followed
by reductive removal of the phenylselenenyl group was found to give 2,5-cis
disubstituted tetrahydrofurans with excellent stereocontrol. Using this
procedure, (2S,4S,8R,6Z)-9-benzyloxy-2-tert-butyldiphenylsilyloxy-8-methylnon-6
en-4-ol (11), prepared stereoselectively via the tin(iv) chloride promoted
reaction between the (R)-5-benzyloxy-4-methylpent-2-enyl(tributyl)stannane (3)
and (S)-3-tert-butyldiphenylsilyloxybutanal (10), gave (2S,3R,6S,8S)-1-benzyloxy
8-tert-butyldiphenylsilyloxy-3,6-epoxy-2-methylnonane (13) after deselenation.
This tetrahydrofuran was selectively deprotected, oxidized and esterified to give
methyl nonactate (2). Having established this synthesis of 2,5-cis-disubstituted
tetrahydrofurans, it was applied to complete a synthesis of pamamycin 607 (1).
(2S,3R,6S,8R)-1-Benzyloxy-8-[N-methyl-N-(toluene-4-sulfonyl)amino]-3,6-epoxy-2
methylundecane (35) was prepared stereoselectively from (R)-3-[N-(toluene-4
sulfonyl)-N-methylamino]hexanal (32) by reaction with the stannane 3 followed by
cyclisation of the resulting alkenol 33 and deselenation. Following debenzylation
and oxidation, an aldol reaction of the aldehyde 37 using the lithium enolate of
2,6-dimethylphenyl propanoate (61) gave mainly the 2,3-anti-3,4-syn-adduct 48.
After protection of the secondary alcohol as its tert-butyldimethylsilyl ether
49, reduction using DIBAL-H and oxidation, the resulting aldehyde,
(2S,3S,4R,5R,8S,10R)-3-tert-butyldimethylsilyloxy-2,4-dimethyl-5,8-epoxy-10-[N
methyl-N-(toluene-4-sulfonyl)amino]tridecanal (62), was taken through to the bis
tetrahydrofuran 65 by repeating the sequence of the reactions with the stannane
3, cyclisation and deselenation. The N-(toluene-4-sulfonyl) group was then
replaced by an N-(tert-butoxycarbonyl) group and O-debenzylation and oxidation
gave the carboxylic acid 70 that corresponds to the C(1)-C(18) fragment of
pamamycin 607 (1). Similar chemistry was used to prepare the C(1')-C(11')
fragment 89 of the pamamycin, except that in this case the configuration of the
secondary alcohol introduced by the allylstannane reaction had to be inverted
using a Mitsunobu reaction before the cyclisation. Esterification of the
carboxylic acid of the C(1)-C(18)-fragment 70 using the alcohol 89 of the C(1')
C(11') fragment followed by selective deprotection, macrocyclisation, N
deprotection and N-methylation gave pamamycin 607 (1) that was identical to a
sample of the natural product.
PMID- 23154489
TI - Topical dorzolamide therapy for taxane-related macular oedema.
PMID- 23154488
TI - The effect of imatinib mesylate on the proliferation, invasive ability, and
radiosensitivity of retinoblastoma cell lines.
AB - PURPOSE: Our aim was to evaluate the potential effect of imatinib mesylate (IM),
a small molecule that specifically inhibits the tyrosine quinase receptors, on
the proliferation and invasive abilities of two human retinoblastoma (Rb) cell
lines. Furthermore, the ability of IM to radiosensitize Rb cells was evaluated.
The potential targets of IM (C-kit, PDGRF-alpha and -beta, and c-Abl) were also
investigated in these cell lines. METHODS: Two human Rb cell lines (WERI-RB-1 and
Y79) were cultured under normal growth conditions. An MTT-based proliferation
assay and a Matrigel invasion assay were performed with and without exposure to
10 MUM of IM. The cells were also irradiated with graded dosages of 0, 2, 4, 6,
8, and 10 Gy with and without IM and their proliferations rates were analyzed.
Western blot and immunocytochemical analysis of cytospins were performed to
evaluate the expression of C-kit, PDGRF-alpha and -beta, and c-Abl. RESULTS: When
IM was added to both cell lines a statistically significant (P<0.05) reduction in
proliferation and invasive ability were observed. Exposure to IM also
significantly increased the radiosensitivity of both Rb cell lines. The c-Abl
expression was strongly positive, PDGRF-alpha and -beta expression were also
positive but the C-kit expression was negative in both cell lines. CONCLUSIONS:
These results indicate that Gleevec may be useful as an adjuvant treatment in Rb
patients, specially those considered for radiation therapy.
PMID- 23154490
TI - Cellular and subbasal nerve alterations in early stage Fuchs' endothelial corneal
dystrophy: an in vivo confocal microscopy study.
AB - PURPOSE: To analyze the morphology and density of corneal epithelial cells,
keratocytes, and subbasal nerves, in patients with early stage Fuchs' endothelial
corneal dystrophy (FECD) by in vivo confocal microscopy (IVCM). METHODS: IVCM
(Confoscan 4, Nidek, Inc.) of the central cornea was performed in 30 corneas of
30 patients with early stage FECD and 13 corneas of 13 normal controls. Images
were analyzed for morphology and density of the superficial and basal epithelial
cells, keratocyte density, endothelial cell density (ECD), as well as subbasal
corneal nerve parameters. Central corneal thickness (CCT) was measured in all
patients and normals by ultrasound pachymetry. RESULTS: The ECD was significantly
lower (-45.5%, P<0.001) in FECD patients as compared with controls. Total number
of nerves and main nerve trunks were significantly reduced (-46.3%, P<0.001;
39.7%, P<0.001) in patients with FECD. Posterior keratocyte density was
significantly higher in FECD patients (P<0.001). Significant inverse correlations
were found between CCT and total number of nerves (r=-0.69, P<0.001), CCT and
main nerve trunks (-0.47, P=0.016), as well as CCT and total nerve length (r=
0.62, P=0.006). Significant correlation was found between ECD and total number of
nerves (r=0.44, P=0.012) as well as between ECD and main nerve trunks (r=0.65,
P<0.001). CONCLUSIONS: IVCM demonstrates alterations in corneal innervation in
patients with early stage FECD, suggesting a potential role of corneal nerves in
the pathogenesis of FECD. Additional studies are required to investigate whether
subbasal nerve alterations are caused by nonspecific corneal edema, from FECD
induced decrease in ECD, or potentially leading to loss of endothelial cells.
PMID- 23154491
TI - Proliferative diabetic retinopathy in long-term diabetic patients with and
without clinical osteoarthritis.
AB - OBJECTIVE: To determine whether some long-term diabetic patients with coexisting
clinical osteoarthritis (OA) are less likely to develop diabetic retinopathy (DR)
than other diabetic patients and whether there is a relation between the timing
of the clinical OA onset and DR. DESIGN, SETTING, AND PARTICIPANTS: Retrospective
case-control study of 85 osteoarthritic patients with 20 years or more diabetes
(A/DM) control group and of 85 non-osteoarthritic diabetic patients (NoA/DM)
matched for age, race, duration, and type of diabetes. Digital fundus photographs
were graded for retinopathy in masked manner. RESULTS: Glycosylated hemoglobin,
hypertension, and smoking showed no significant difference. Twelve out of 85
patients (12.9%) in A/DM group developed proliferative diabetic retinopathy (PDR)
whereas 79/85 (92.9%) NoA/DM patients developed PDR (P<0.001). The onset of OA
symptoms was known in 80/85 of the A/D patients, including 47 patients with onset
before or at the same year as DM and 33 patients with relative onset after the
year of DM. All the 10 patients with PDR (10/33) developed OA subsequent to their
initiation for diabetic treatment while 0/47 A/DM patients with the onset of
osteoarthritic symptoms present before or the same year as their onset of
diabetes developed PDR (P<0.001). CONCLUSION: Our study suggests that in long
term DM, PDR was significantly associated with the absence of concomitant
clinical OA. This observation was highly significant if the onset of the
arthritis was the same year or before the onset of the diabetes.
PMID- 23154493
TI - Response to Tatham and Brookes.
PMID- 23154492
TI - The pathology of ocular cancer.
AB - Primary cancers of the eye are rare. These include uveal melanoma, a tumor that
preferentially affects the choroid of light-eyed, fair-skinned Europeans, and the
pediatric retinal neoplasm retinoblastoma, which is slightly more common
worldwide. Uveal melanoma kills about half of affected patients. Most succumb to
hepatic metastases, which are unresponsive to current therapy. Factors indicative
of poor prognosis include tumor size, ciliary body involvement, epithelioid
cells, extraocular extension, lymphocytic and melanophagic infiltration, mitotic
activity, vascular mimicry patterns, and most importantly, the detection of
monosomy 3 and class 2 gene expression profile in tumor cells using special
tests. Most retinoblastomas are caused by sporadic somatic mutations in the RB1
gene, but about one-third arise in infants with germline mutations. The latter
tend to develop earlier, are often bilateral and are transmissible to offspring
as an autosomal dominant trait. Retinoblastoma displays varying degrees of
differentiation including Homer Wright and Flexner-Wintersteiner rosettes and
photoreceptor differentiation (fleurettes). Rosettes are more common in eyes
enucleated from very young infants. Tumors composed entirely of fleurettes
(retinoma/retinocytoma) are thought to be retinoblastoma precursors, and like
retinoblastoma, harbor mutations in both copies of the RB1 gene. Retinoblastoma
is a major cancer treatment success story in developed countries where most
deaths are caused by secondary tumors in germline mutation carriers. High-risk
histopathological features that are an indication for adjuvant chemotherapy
include massive uveal invasion and retrolaminar optic nerve invasion. Eye-sparing
therapies including brachyradiotherapy and systemic and intra-arterial
chemotherapy have reduced the number of eyes with retinoblastoma requiring
enucleation in recent years.
PMID- 23154494
TI - Reply to Claoue et al.
PMID- 23154495
TI - The effects of Helicobacter pylori infection on intraocular pressure in anterior
uveitis.
AB - PURPOSE: We investigated the influence of H. pylori infection on intraocular
pressure (IOP) in anterior uveitis patients to clarify whether H. pylori
infection is related to high IOP in anterior uveitis. METHODS: In this
prospective study, 165 Korean anterior uveitis patients were examined. All
patients underwent serological analysis to identify the cause of uveitis,
including the presence of H. pylori infection by enzyme-linked immunosorbent
assay. Serological values were compared between patients with and without high
IOP. RESULTS: Seropositivity for H. pylori was 69.70% of patients with high IOP
and 38.38% of patients with normal IOP (P<0.01). CONCLUSION: This study suggests
that H. pylori infection is associated with high IOP in anterior uveitis.
PMID- 23154496
TI - Diagnostic cellular yield is superior with full pars plana vitrectomy compared
with core vitreous biopsy.
AB - PURPOSE: Vitreous biopsy for the cytological assessment of suspected intraocular
lymphoma and vitritis of uncertain aetiology is a standard investigation. The
types of specimens generated and the diagnostic rate are variable within and
between centres. There are many reasons for this but one observation that has not
been considered previously is the differential distribution of cells in the
vitreous gel. To test this possibility, five consecutive patients with suspected
vitreous involvement by lymphoma or vitritis of uncertain aetiology underwent a
core vitreous biopsy immediately before a planned full pars plana vitrectomy
(PPV) and the cellularity of the two sampling techniques compared. METHODS: A
prospective study of five consecutive patients requiring vitreous sampling to
secure a firm diagnosis. For each of five patients, the core vitreous biopsy
specimen was received in a universal tube and the PPV specimen was received in a
vitreous cassette. Fluid (0.25 ml) was removed from both specimens, centrifuged
and haematoxylin and eosin (H&E) stained slides prepared per sampling method. The
slides were examined with a light microscope, the most cellular field selected
and the number of cells per mm(2) counted and compared between sampling
techniques. RESULTS: PPV specimen's, revealed a cellularity range that was 7.4 to
78 * (average 31 *) greater than a core vitreous biopsy. In the two cases of a
final diagnosis of intraocular lymphoma, the vitreous core biopsy was non
diagnostic. Furthermore, the PPV specimen generated additional cellular material
for numerous ancillary investigations to permit a secure diagnosis. CONCLUSIONS:
The results of this differential vitreous sampling study has strengthened our
anecdotal slit lamp clinical observations that inflammatory cells and lymphoma
cells are concentrated more in the cortical vitreous. Therefore, vitreous cells
have less chance to be sampled if a single core vitreous biopsy is performed.
Indeed, the two cases of confirmed lymphoma generated a non-diagnostic core
vitreous biopsy. In our centre, this study has lead to PPV being performed as a
gold standard on all patients with suspected intraocular lymphoma or vitritis of
uncertain aetiology.
PMID- 23154497
TI - A case of arrested primary congenital glaucoma.
PMID- 23154499
TI - Clinical characteristics of peripheral exudative hemorrhagic chorioretinopathy
and its response to bevacizumab therapy.
PMID- 23154498
TI - Diagnostic incisional biopsies in clinically indeterminate choroidal tumours.
AB - Most intraocular tumours are reliably diagnosed by a careful clinical examination
combined with one or more non-invasive diagnostic techniques. However, in a small
percentage of tumours, typically small and clinically amelanotic, the features
are insufficiently distinct for a confident clinical diagnosis and tissue is
required for diagnosis. We used a 23-G vitreous cutter to access the biopsy site
in 43 patients with clinically indeterminate tumours. After retinotomy, an
incisional choroidal biopsy yielded a specimen of ~1 mm(3). Obtained tissue was
routinely processed for light microscopy including an immunohistochemical panel
of monoclonal antibodies. Adequate tissue for diagnosis was provided in 41/43
(95%) patients. The sensitivity and specificity to detect malignant disease were
0.97 and 1.00, respectively. The positive predictive value was 1.00.
Complications included progression of pre-existing retinal detachment in 5/43
(12%) patients and transient rise in intraocular pressure to >40 mm Hg in 6/43
(14%) patients; 4 of these 6 patients had a pre-existing retinal detachment. No
patient with a pre-operatively attached retina had a retinal detachment. We
conclude that an incisional transretinal choroidal biopsy yields abundant
material and may adequately confirm or exclude malignancy in patients with
clinically indeterminate tumours. The complication rate can be minimised when
patients with pre-existing retinal detachment are excluded from biopsy.
PMID- 23154500
TI - 20-gauge and 23-gauge phacovitrectomy for idiopathic macular holes: comparison of
complications and long-term outcomes.
AB - PURPOSE: To assess and compare the complications and long-term visual and
anatomical outcomes of 20- and 23-gauge phacovitrectomy (PVT) for idiopathic
macular hole repair. METHODS: A retrospective, consecutive, interventional case
series of 72 eyes with idiopathic macular holes were managed with 20-gauge PVT
(n=36) or 23-gauge PVT (n=36). All patients underwent a posterior-chamber intra
ocular lens implantation and internal-limiting-membrane peel with the aid of
either trypan blue or brilliant blue G(250) dyes. RESULTS: The macular hole
closure rate was 97% with 20-gauge PVT and 100% with 23-gauge PVT. Mean follow-up
was 24.06 (+/-12.83) months with 20-gauge PVT and 17.47 (+/-5.79) with 23-gauge
PVT. Mean visual acuity improvement in LogMar was 0.41 (+/-0.32) with 20-gauge
PVT and 0.52 (+/-0.25) with 23-gauge PVT (P=0.135). The incidence of retinal
breaks was higher with the 20-gauge PVT compared with the 23-gauge PVT, occurring
in 13 (36.1%) and 4 (11.1%) cases, respectively (P=0.025). There were no cases of
retinal detachment. Postoperative intraocular pressure (IOP), at day 1, was
significantly higher with 20-gauge PVT at 24.77 (+/-12.68) mm Hg compared with
17.20 (+/-6.95) mm Hg in 23-gauge PVT (P=0.0028). Operating times were longer in
20-gauge PVT at 89.36 (+/-15.26) min compared with the 23-gauge PVT at 79.33 (+/
23.82) min (P=0.04). CONCLUSION: The 20-gauge PVT compared with 23-gauge PVT for
macular hole repair is a slightly longer procedure and was associated with an
increased incidence of retinal breaks and short-term elevated IOP. Both
techniques have comparable visual and anatomical outcomes, but the 23-gauge PVT
has advantages with regard to safety profile and operating time.
PMID- 23154501
TI - 5 years review of periocular basal cell carcinoma and proposed follow-up
protocol.
AB - AIM: (1) To investigate the recurrence of periocular basal cell carcinoma (BCC)
reported as completely excised on histology. (2) To identify risks associated
with recurrence. (3) To recommend a rational follow-up protocol. METHODS: This is
a cohort study by case note review of consecutive patients undergoing excision of
periocular BCC between 2000 and 2006 at University Hospitals of Leicester. All
lesions were excised with 3 mm clinical margin and the defect reconstructed only
after the excision margin was declared clear. RESULTS: A total of 413 episodes of
surgical excision were recorded for 270 patients over the 7-year period of 2000
2006. All of them have 5 years follow-up. Mean age 73.7 (+/-12.5). In all, 67%
were nodular BCC and 45.4% located in the lower eyelid. The main outcome measure
was the recurrence rate. None of the patients with primary nodular BCC suffered
recurrence. The recurrence rate for primary morphoeaform BCC following complete
excision is 3.8%. In total, 8.1% of patients had several lesions simultaneously
whereas 7.8% patients had BCC in multiple locations subsequently (metachronous).
Three patients who had previously recurrent BCC (rBCC) treated elsewhere or not
using this method had orbital/lacrimal drainage system involvement requiring
exenteration. CONCLUSION: We recommend that patients with a single, completely
excised primary solid or nodular BCC can be discharged after one 6-monthly
review, although they should be instructed to monitor for the development of
further lesions. The incidence of recurrence for primary morphoeaform BCC is 3.8%
and for rBCC is 3.6% over 5 years and these patients should stay under review for
this period.
PMID- 23154502
TI - Long-term evaluation of patients treated with dexamethasone intravitreal implant
for macular edema due to retinal vein occlusion.
AB - PURPOSE: To evaluate the long-term visual prognosis and complications of patients
who received intravitreal Ozurdex injections for the treatment of macular edema
(ME) due to retinal vein occlusion (RVO). METHODS: A total of 17 patients who
received Ozurdex injections in our institution as part of the GENEVA study were
recalled for examination. Recorded parameters included final visual acuity (VA),
final retinal thickness by optical coherence tomography, persistence of ME, and
the occurrence of any complications. RESULTS: Mean follow-up time was 50.5
months. Patients with branch RVO (BRVO) had a more favorable prognosis than
central RVO (CRVO), and their mean VA had improved significantly, whereas the
mean VA for the patients with CRVO did not improve significantly. Retinal
thickness had reduced significantly in the whole group and in each subgroup
separately. Complications included 10 patients with cataract progression, 1 with
elevated intraocular pressure, and 1 with neovascularization and vitreous
hemorrhage. CONCLUSIONS: This is the first reported long-term evaluation of
patients treated with Ozurdex. Our results indicate that it has favorable long
term safety profile, and may have a beneficial effect on the visual prognosis in
BRVO even in the absence of continuous treatment. Further research is required to
establish the optimal retreatment schedule for Ozurdex.
PMID- 23154503
TI - Intra-familial tests of association between familial idiopathic scoliosis and
linked regions on 9q31.3-q34.3 and 16p12.3-q22.2.
AB - OBJECTIVE: Custom genotyping of markers in families with familial idiopathic
scoliosis were used to fine-map candidate regions on chromosomes 9 and 16 in
order to identify candidate genes that contribute to this disorder and prioritize
them for next-generation sequence analysis. METHODS: Candidate regions on 9q and
16p-16q, previously identified as linked to familial idiopathic scoliosis in a
study of 202 families, were genotyped with a high-density map of single
nucleotide polymorphisms. Tests of linkage for fine-mapping and intra-familial
tests of association, including tiled regression, were performed on scoliosis as
both a qualitative and quantitative trait. RESULTS AND CONCLUSIONS: Nominally
significant linkage results were found for markers in both candidate regions.
Results from intra-familial tests of association and tiled regression
corroborated the linkage findings and identified possible candidate genes
suitable for follow-up with next-generation sequencing in these same families.
Candidate genes that met our prioritization criteria included FAM129B and CERCAM
on chromosome 9 and SYT1, GNAO1, and CDH3 on chromosome 16.
PMID- 23154504
TI - Dietary lipid-dependent regulation of de novo lipogenesis and lipid partitioning
by ketogenic essential amino acids in mice.
AB - BACKGROUND: We have previously reported that dietary ketogenic amino acids (KAAs)
modulate hepatic de novo lipogenesis (DNL) and prevent hepatic steatosis in mice.
However, the dependence of the metabolic phenotypes generated by KAA on the type
of dietary lipid source remains unclear. OBJECTIVE: The aim of this study was to
assess the effect of KAA combined with different dietary lipid sources on hepatic
DNL and tissue lipid partitioning in mice. DESIGN: We compared three different
KAA-supplemented diets, in which a portion of the dietary protein was replaced by
five major essential amino acids (Leu, Ile, Val, Lys and Thr) in high-fat diets
based on palm oil (PO), high-oleic safflower oil (FO) or soy oil (SO). To compare
the effects of these diets in C57B6 mice, the differential regulation of DNL and
dietary lipid partitioning due to KAA was assessed using stable isotopic flux
analysis. RESULTS: The different dietary oils showed strikingly different
patterns of lipid partitioning and accumulation in tissues. High-PO diets
increased both hepatic and adipose triglycerides (TG), whereas high-FO and high
SO diets increased hepatic and adipose TG, respectively. Stable isotopic flux
analysis revealed high rates of hepatic DNL in high-PO and high-FO diets, whereas
it was reduced in the high-SO diet. KAA supplementation in high-PO and high-FO
diets reduced hepatic TG by reducing the DNL of palmitate and the accumulation of
dietary oleate. However, KAA supplementation in the high-SO diet failed to reduce
hepatic DNL and TG. Interestingly, KAA reduced SO-induced accumulation of hepatic
linoleate and enhanced SO-induced accumulation of dietary oleate. CONCLUSIONS:
Overall, the reduction of hepatic TG by KAA is dependent on dietary lipid sources
and occurs through the modulation of DNL and altered partitioning of dietary
lipids. The current results provide further insight into the underlying
mechanisms of hepatic lipid reduction by amino acids.
PMID- 23154505
TI - Allelic differences in Medicago truncatula NIP/LATD mutants correlate with their
encoded proteins' transport activities in planta.
AB - Medicago truncatula NIP/LATD gene, required for symbiotic nitrogen fixing nodule
and root architecture development, encodes a member of the NRT1(PTR) family that
demonstrates high-affinity nitrate transport in Xenopus laevis oocytes. Of three
Mtnip/latd mutant proteins, one retains high-affinity nitrate transport in
oocytes, while the other two are nitrate-transport defective. To further examine
the mutant proteins' transport properties, the missense Mtnip/latd alleles were
expressed in Arabidopsis thaliana chl1-5, resistant to the herbicide chlorate
because of a deletion spanning the nitrate transporter AtNRT1.1(CHL1) gene. Mtnip
3 expression restored chlorate sensitivity in the Atchl1-5 mutant, similar to
wild type MtNIP/LATD, while Mtnip-1 expression did not. The high-affinity nitrate
transporter AtNRT2.1 gene was expressed in Mtnip-1 mutant roots; it did not
complement, which could be caused by several factors. Together, these findings
support the hypothesis that MtNIP/LATD may have another biochemical activity.
PMID- 23154506
TI - Sugar-induced endocytosis of plant 7TM-RGS proteins.
AB - Plant cells use sugars mainly as a source or store of energy and carbon skeletons
for anabolic reactions and for osmotic regulation. The perception of sugars and
their responses are rather complex including the heterotrimeric G protein pathway
and a seven-transmembrane RGS molecule. Previously, we found that endocytosis of
the 7TM-RGS leads to sustained activation of the G protein pathway in the genetic
model Arabidopsis. Here we show that other plants possess similar endocytosis
systems of the 7TM-RGS proteins. A phosphorylation site essential for the
endocytosis is well conserved in land plant 7TM-RGS proteins. In addition,
conifer and tobacco 7TM-RGS proteins are internalized in response to sugar. These
results indicate a universal mechanism to activate G signaling by endocytosis in
plant cells that have 7TM-RGS proteins.
PMID- 23154507
TI - Sequence diversity and conservation in factors influencing succinate
dehydrogenase flavinylation.
AB - The mitochondrial enzyme succinate dehydrogenase (SDH) consists of four subunits,
a flavoprotein (SDH1), an iron-sulfur (Fe-S) protein (SDH2) and two integral
membrane subunits (SDH3/SDH4). In mammals and yeast, an assembly factor termed
SDHAF2/SDH5 is required for accumulation of flavinylated SDH1. In Arabidopsis, we
have recently reported the characterization of an unknown function protein with
low sequence similarity to SDHAF2 that is needed for assembly and activity of SDH
and also for normal root elongation. (1) In this short communication, we have
reviewed the sequence diversity and conservation of SDHAF2 across kingdoms based
on phylogenetic analysis. Given that flavinylation of SDH is dependent on the
SDH1:SDHAF2 interaction, we have also discussed the conservation of the C
terminal tail of SDH1, which is required for this interaction process. In
combination, we provide comparative evidence for a conserved role of SDHAF2 as an
assembly factor from animals to plants.
PMID- 23154508
TI - Possible function of VIPP1 in thylakoids: protection but not formation?
AB - VIPP1 protein in photosynthetic organisms is homologous to bacterial PspA, which
protects plasma membrane integrity upon stresses. Despite the proposed role of
VIPP1 in thylakoid biogenesis, its precise function remains unclear. Recently,
our in-depth analysis of Arabidopsis vipp1 mutants revealed VIPP1's involvement
in the maintenance of chloroplast envelopes. Chloroplasts in intact vipp1 leaves
exhibited spherical balloon-like morphology, which resulted from osmotic stress
across envelopes. In fact, observation of VIPP1 fused to green fluorescence
protein in vivo revealed that most VIPP1 is localized as a lattice-like macro
complex attached along with the envelope. Because of the proposed function in
thylakoids, we examined whether vipp1 also exhibited altered morphologies in
thylakoids. Results show that thylakoid morphologies were detected irregularly,
but vipp1 chloroplasts retained normal-appearing grana stacks. We infer that
VIPP1 might influence thylakoids as well as envelopes, but that it is not
involved directly in thylakoid membrane formation.
PMID- 23154509
TI - Circadian clock and PIF4-mediated external coincidence mechanism coordinately
integrates both of the cues from seasonal changes in photoperiod and temperature
to regulate plant growth in Arabidopsis thaliana.
AB - In Arabidopsis thaliana, the circadian clock regulates the photoperiodic plant
growth including the elongation of hypocotyls in a short-days (SDs)-specific
manner. The clock-controlled PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) gene
encoding a basic helix-loop-helix (bHLH) transcription factor plays crucial roles
in this regulation. The SDs-specific elongation of hypocotyls is best explained
by accumulation of the active PIF4 proteins at the end of night specifically in
SDs due to coincidence between internal (circadian clock) and external
(photoperiod) cues. However, this external coincidence model was challenged with
the recent finding that the elongation of hypocotyls is markedly promoted at high
growth temperature (28C) even in long-days (LDs), implying that the model to
explain the photoperiodic response of plant architecture appears to be
conditional on ambient temperature. With regard to this problem, the results of
this and previous studies showed that the model holds under a wide range of
ambient temperature conditions (16C to 28C). We propose that the circadian clock
and PIF4-mediated external coincidence mechanism coordinately integrates both of
the cues from seasonal changes in photoperiod and temperature to regulate plant
growth in natural habitats.
PMID- 23154510
TI - CDC48 function during TMV infection: regulation of virus movement and replication
by degradation?
AB - Cell-division-cycle protein 48 (CDC48) is an essential, conserved ATP-driven
chaperone in eukaryotic cells, which functions in diverse cellular processes
including the targeting of misfolded and aggregated proteins for degradation via
proteasomal and aggresomal-autophagic pathways. We recently demonstrated that
plant CDC48 localizes to and interacts with Tobacco mosaic virus (TMV) movement
protein (MP) in ER-associated viral protein inclusions. Our data suggest that
CDC48 participates in the clearance of these viral protein inclusions in an ER
assisted protein degradation (ERAD)-like mechanism. As TMV MP-inclusions formed
at late infection stages resemble aggresomes, we here propose that TMV MP enters
both, ERAD-like and aggresomal pathways in its host cells and that CDC48
coordinates these processes. Moreover, as viruses often exploit host pathways for
replication and spread, we propose a model in which CDC48 functions in the
degradation pathway of overaccumulating viral protein and also actively
participates in the regulation of TMV replication and cell-to-cell movement.
PMID- 23154511
TI - News about cryptochrome photoreceptors in algae.
AB - Cryptochromes (CRYs) are flavoproteins that are known as blue light
photoreceptors in many organisms. Recently, genome sequences from a variety of
algae became available. Functional characterizations of animal-like CRYs from
Oestreococcus tauri, Chlamydomonas reinhardtii and Phaeodactylum tricornutum
highlighted novel functions and properties. As arising from studies in fungi,
certain algal CRYs of the "cryptochrome photolyase family" (PtCPF1, OtCPF1) have
dual or even triple functions. They are involved in blue light perception and/or
in the circadian clock and are able to repair DNA damages. On the other hand, the
animal-like aCRY from C. reinhardtii is not only acting as sensory blue light-
but also as sensory red light receptor thus expanding our current view of
flavoproteins in general and CRYs in particular. The observed broad spectral
response points to the neutral radical state of flavin, which is assumed to be
the dark form in aCRY in contrast to the plant CRYs.
PMID- 23154512
TI - Loss of expression of the double strand break repair protein ATM is associated
with worse prognosis in colorectal cancer and loss of Ku70 expression is
associated with CIN.
AB - Repair of double strand DNA breaks (DSBs) is pivotal in maintaining normal cell
division and disruption of this system has been shown to be a key factor in
carcinogenesis. Loss of expression of the DSB repair proteins have previously
been shown to be associated with poorer survival in colorectal cancer. We wished
to ascertain the relationship of altered expression of the DSB repair proteins
gamma-H2AX (gamma-H2AX), ATM and Ku70 with biological and clinico-pathological
features of colorectal cancer. 908 tumours from the VICTOR clinical trial of
stage II/III colorectal cancer were analysed for expression of gamma-H2AX, ATM
and Ku70 using immunohistochemistry. Expression levels were correlated with CIN
and with disease-free survival, correcting for microsatellite instability,
BRAF/KRAS mutation status, Dukes stage, chemo/radiotherapy, age, gender and
tumour location. Down-regulated Ku70 expression was associated with chromosomal
instability (p=0.029) in colorectal cancer. Reduced ATM expression was an
independent marker of poor disease-free survival (HR=1.67, 95% CI 1.11-2.50,
p=0.015). For Ku70, further studies are required to investigate the potential
relationship of non-homologous end joining with chromosomal instability. Loss of
ATM expression might serve as a biomarker of poor prognosis in colorectal cancer.
PMID- 23154513
TI - Effect of ultrasound treatment on brain edema in a traumatic brain injury model
with the weight drop method.
AB - BACKGROUND: For the treatment of traumatic brain edema, an efficient modality has
not yet emerged. There have been many studies to date which have reported the
employment of low-frequency ultrasound for blood-brain barrier disruption (BBBD).
However, the authors have observed that low-intensity ultrasound increases water
permeability without cellular damage in cartilage cells. We have therefore
attempted to observe the effects of applying this low-intensity ultrasound to an
experimental animal model. METHODS: A traumatic brain injury rat model was
established according to the weight drop method developing the traumatic brain
edema. The degree of BBBD was measured by the changes in the water content and
spectrophotometric absorbance of Evans blue dye in the cerebrum after low
frequency ultrasound. RESULTS: The cerebral water content levels showed that the
BBBD gradually increased after impact and thereafter decreased after 6 h. After
low-frequency ultrasound exposure, the values of water content and
spectrophotometric absorbance of Evans blue dye were the lowest at 0 h, and were
increased at 2 and 5 h of ultrasonic exposure (after impact). CONCLUSION: We
suggest that traumatic brain edema in the rat model may be alleviated by low
frequency ultrasound, and low-frequency ultrasound might be proposed as a novel
treatment modality for brain edema.
PMID- 23154514
TI - A novel route to prepare LaNiO3 perovskite-type oxide nanofibers by
electrospinning for glucose and hydrogen peroxide sensing.
AB - Perovskite-type oxide LaNiO(3) nanofibers (LNFs) have been successfully
synthesized by electrospinning and sequential calcinations. The electrospun LNFs
modified carbon paste electrode was used to construct a nonenzymatic hydrogen
peroxide (H(2)O(2)) sensor and glucose biosensor for the first time. The LNFs
composition was verified by X-ray diffraction, and the morphologies were examined
by scanning electron microscopy and transmission electron microscopy. Cyclic
voltammetry and amperometry were used to evaluate the catalytic activity of the
LNFs modified electrode towards H(2)O(2) and glucose. By using LNFs as
electrocatalysts, the modified electrode showed high electrocatalytic activity
for the oxidation of H(2)O(2) and glucose. Under the optimized conditions, the
H(2)O(2) sensor exhibited a low detection limit down to 33.9 nM with a wide
linear range from 0.05 to 1000 MUM. The nonenzymatic sensor also showed fast
response, long-term stability as well as a low detection limit for glucose.
PMID- 23154515
TI - Preparation of graphite-like carbon nitride nanoflake film with strong
fluorescent and electrochemiluminescent activity.
AB - The preparation, characterization, fluorescence (FL) and electrochemiluminescence
(ECL) of graphite-like carbon nitride nanoflake particles (g-C(3)N(4) NFPs) and
nanoflake films (g-C(3)N(4) NFFs) have been reported. Highly water-dispersible g
C(3)N(4) NFPs with a height of ~5 to 35 nm and a lateral dimension of ~40 to 220
nm have been extracted from bulk g-C(3)N(4) materials by chemical oxidation. New,
stable and defined g-C(3)N(4) NFFs can be easily obtained by drying NFPs on
certain hydrophilic substrates such as glass or electrode surfaces. Both g
C(3)N(4) NFPs and g-C(3)N(4) NFFs have good FL activities, i.e. they can give
strong blue light (435 nm) emission under UV light (365 nm) excitation. The as
prepared g-C(3)N(4) NFFs on a glassy carbon electrode exhibit strong non-surface
state ECL activity in the presence of reductive-oxidative coreactants, including
dissolved oxygen (O(2)), hydrogen peroxide (H(2)O(2)) and peroxydisulfate
(S(2)O(8)(2-)) and give rise to blue light emission (435 nm), which is the same
as the wavelength of FL. The non-surface state ECL mechanisms of the g-C(3)N(4)
NFF-coreactant systems have been studied and discussed in detail.
PMID- 23154517
TI - Responding to a diagnosis of localized prostate cancer: men's experiences of
normal distress during the first 3 postdiagnostic months.
AB - BACKGROUND: Men experience localized prostate cancer (PCa) as aversive and
distressing. Little research has studied the distress men experience as a normal
response to PCa, or how they manage this distress during the early stages of the
illness. OBJECTIVES: The objective of this study was to explore the experience of
men diagnosed with localized PCa during their first postdiagnostic year. METHODS:
This constructivist qualitative study interviewed 8 men between the ages of 44
and 77 years, in their homes, on 2 occasions during the first 3 postdiagnostic
months. Individual, in-depth semistructured interviews were used to collect the
data. RESULTS: After an initial feeling of shock, the men in this study worked
diligently to camouflage their experience of distress through hiding and
attenuating their feelings and minimizing the severity of PCa. CONCLUSIONS: Men
silenced distress because they believed it was expected of them. Maintaining
silence allowed men to protect their strong and stoic self-image. This
stereotype, of the strong and stoic man, prevented men from expressing their
feelings of distress and from seeking support from family and friends and health
professionals. IMPLICATIONS FOR PRACTICE: It is important for nurses to
acknowledge and recognize the normal distress experienced by men as a result of a
PCa diagnosis. Hence, nurses must learn to identify the ways in which men avoid
expressing their distress and develop early supportive relationships that
encourage them to express and subsequently manage it.
PMID- 23154518
TI - Simultaneous electroanalytical determination of hydroquinone and catechol in the
presence of resorcinol at an SiO2/C electrode spin-coated with a thin film of
Nb2O5.
AB - This paper describes the development, characterization and application of an
Nb(2)O(5) film formed on the surface of a carbon ceramic material, SiO(2)/C,
obtained by a sol-gel method, using the spin-coating technique. The working
electrode using this material will be designated as SiCNb. Hydroquinone and
catechol can be oxidized at this electrode in the presence of resorcinol,
allowing their simultaneous detection. The electrochemical properties of the
resulting electrode were investigated using cyclic and differential pulse
voltammetry techniques. Well-defined and separated oxidation peaks were observed
by differential pulse voltammetry in Tris-HCl buffer solution at pH 7 containing
1 mol L(-1) KCl in the supporting electrolyte solution. The SiCNb electrode
exhibited high sensitivity in the simultaneous determination of hydroquinone and
catechol in the presence of resorcinol, with the limits of detection for
hydroquinone and catechol being 1.6 MUmol L(-1) and 0.8 MUmol L(-1),
respectively. Theoretical calculations were performed to determine the ionization
energies of hydroquinone, catechol and resorcinol; the results were used to
explain the simultaneous determination of species by differential pulse
voltammetry. The presence of resorcinol did not produce any interference in the
simultaneous detection of hydroquinone and catechol on the surface of the
modified electrode.
PMID- 23154516
TI - The PRO-SELF pain control program improves family caregivers' knowledge of cancer
pain management.
AB - BACKGROUND: The majority of cancer treatment is provided in outpatient settings.
Family caregivers' (FCs') knowledge and beliefs about pain and its management are
critical components of effective care. OBJECTIVE: This study's aim was to
evaluate the efficacy of a psychoeducational intervention, compared with control,
to increase FCs' knowledge of cancer pain management. INTERVENTION/METHODS:
Family caregivers of oncology outpatients were randomized together with the
patients into the PRO-SELF Pain Control Program (n = 58) or a control group (n =
54). Family caregivers completed a demographic questionnaire and the Family Pain
Questionnaire (FPQ) at the beginning and end of the study to assess their
knowledge about pain and its management. The intervention consisted of nurse
coaching, home visits, and phone calls that occurred over 6 weeks. RESULTS: One
hundred twelve FCs (60% female) with a mean age of 63 (SD, 10.7) years
participated. Compared with FCs in the control group, FCs in the PRO-SELF group
had significantly higher knowledge scores on all of the single items on the FPQ,
except for the item "cancer pain can be relieved," as well as for the total FPQ
score. CONCLUSION: The use of a knowledge and attitude survey like the FPQ, as
part of a psychoeducational intervention provides an effective foundation for FC
education about cancer pain management. IMPLICATIONS FOR PRACTICE: Oncology
nurses can use FCs' responses to the FPQ to individualize teaching and spend more
time on identified knowledge deficits. This individualized approach to FC
education may save staff time and improve patient outcomes.
PMID- 23154519
TI - Percutaneous cytologic diagnosis of solid pseudopapillary tumors of pancreas in
children.
AB - Solid pseudopapillary tumors of the pancreas, formerly known as Frantz tumors,
are rare exocrine tumors that electively affect young women in their second and
third decades of life, and are rarely observed in children. Histologic
confirmation is nevertheless desirable before proceeding with treatment of
pancreatic lesions, as appropriate treatment can range from conservative to
ablative surgery. Here, we report 3 cases of solid pseudopapillary tumors of the
pancreas and we postulate that percutaneous cytologic sample analysis (instead of
biopsy) may be sufficient to reach an accurate diagnosis and eliminate
differential diagnosis.
PMID- 23154520
TI - Paraganglioma presenting with marked proteinuria: a case report.
AB - Paragangliomas are rare neuroendocrine tumors that arise from sympathetic and
parasympathetic paraganglia. In children, most of them are functional tumors.
Presenting symptoms such as sustained or paroxysmal elevations in blood pressure,
headache, sweating, and palpitations are related to catecholamine hypersecretion.
A previously healthy 8-year-old boy presented with marked proteinuria,
hypertension, and heart murmur. Imaging revealed an 81*43*45 mm sized solid mass
extending from right retroaortic area to left suprarenal region. Measurements of
catecholamines suggested the diagnosis of paraganglioma. Pathologic examination
confirmed the diagnosis. Complete tumor resection was performed. Proteinuria,
hypertension, and cardiac signs resolved after surgery. Proteinuria has been
described as a rare manifestation of paragangliomas in adult patients. This is
the first case of a paraganglioma presenting with massive proteinuria in a child.
PMID- 23154522
TI - Combining transition metal catalysis and organocatalysis--an update.
AB - The combination of transition metal catalysis and organocatalysis as a new and
exciting research area has attracted increasing attention as it can enable the
development of unprecedented transformations that is not possible by use of
either of the catalytic systems alone, and can improve the reactivity, efficiency
and stereocontrol of existing chemical transformations. In this review, we
summarize recent remarkable progress in the field of combined transition metal
catalysis and organocatalysis, further highlighting the potential of this new and
exciting research area and the many challenges that still remain for the future.
PMID- 23154521
TI - Structural and electrical characterization of ultra-thin SrTiO3 tunnel barriers
grown over YBa2Cu3O7 electrodes for the development of high Tc Josephson
junctions.
AB - The transport properties of ultra-thin SrTiO(3) (STO) layers grown over
YBa(2)Cu(3)O(7) electrodes were studied by conductive atomic force microscopy at
the nano-scale. A very good control of the barrier thickness was achieved during
the deposition process. A phenomenological approach was used to obtain critical
parameters regarding the structural and electrical properties of the system. The
STO layers present an energy barrier of 0.9 eV and an attenuation length of 0.23
nm, indicating very good insulating properties for the development of high
quality Josephson junctions.
PMID- 23154524
TI - Ethical dilemmas associated with genetic testing: which are most commonly seen
and how are they managed?
AB - PURPOSE: The aim of this study was to document the range and frequency of ethical
dilemmas associated with genetic testing encountered by genetic health
professionals and to determine the strategies used to manage them. METHODS: An
online survey was used to document how often the 11 key ethical dilemmas have
been encountered; whether any additional dilemmas have been encountered; and how
these dilemmas have been managed. Members of the Australasian Association of
Clinical Geneticists, Australasian Society of Genetic Counsellors, and genetic
social workers practicing in Australia and New Zealand were invited to
participate. RESULTS: A total of 102 responses were received (31% response rate).
Respondents had encountered all of the 11 ethical dilemmas included in the
survey, and 18 respondents had encountered 14 additional dilemmas. Respondents
encountered an average of 2.2 dilemmas per year of practice. Peer and clinical
supervision were the most common strategies used to manage dilemmas, and seeking
advice from clinical ethics committees was rare. Occasionally, respondents
facilitated practices they deemed unethical as a consequence of client deception.
CONCLUSION: Ethical dilemmas of genetic testing are encountered regularly in
clinical genetics practice. Evidence provided by our study can assist in
targeting training, support, and guidance to help genetic health professionals
navigate such dilemmas in the future.
PMID- 23154523
TI - Comparative analysis of IRF6 variants in families with Van der Woude syndrome and
popliteal pterygium syndrome using public whole-exome databases.
AB - PURPOSE: Mutations in the transcription factor IRF6 cause allelic autosomal
dominant clefting syndromes, Van der Woude syndrome, and popliteal pterygium
syndrome. We compared the distribution of IRF6 coding and splice-site mutations
from 549 families with Van der Woude syndrome or popliteal pterygium syndrome
with that of variants from the 1000 Genomes and National Heart, Lung, and Blood
Institute Exome Sequencing Projects. METHODS: We compiled all published
pathogenic IRF6 mutations and performed direct sequencing of IRF6 in families
with Van der Woude syndrome or popliteal pterygium syndrome. RESULTS: Although
mutations causing Van der Woude syndrome or popliteal pterygium syndrome were
nonrandomly distributed with significantly increased frequencies in the DNA
binding domain (P = 0.0001), variants found in controls were rare and evenly
distributed in IRF6. Of 194 different missense or nonsense variants described as
potentially pathogenic, we identified only two in more than 6,000 controls.
PolyPhen and SIFT (sorting intolerant from tolerant) reported 5.9% of missense
mutations in patients as benign, suggesting that use of current in silico
prediction models to determine function can have significant false negatives.
CONCLUSION: Mutation of IRF6 occurs infrequently in controls, suggesting that for
IRF6 there is a high probability that disruption of the coding sequence,
particularly the DNA-binding domain, will result in syndromic features. Prior
associations of coding sequence variants in IRF6 with clefting syndromes have had
few false positives.
PMID- 23154525
TI - Perspectives of surrogate decision makers for critically ill patients regarding
gene variation research.
AB - PURPOSE: We undertook this investigation to explore the manner in which surrogate
decision makers for critically ill patients perceived genetic data collected in
the context of clinical investigation. METHODS: Surrogate decision makers for
critically ill patients cared for in intensive care units of two urban hospitals
participated in focus groups designed to explore perceptions regarding gene
variation research. RESULTS: Surrogate decision makers were generally familiar
with genetic concepts and reported that they could provide an informed opinion
regarding permitting (or declining) the participation of their loved ones in gene
variation research. Respondents perceived the risk associated with this type of
research largely as the risk associated with acquiring the sample (i.e., whether
it involved an invasive procedure or not) but appreciated that genetic samples
could provide information not readily obtained from nongenetic sources. Concerns
about potential misuse of genetic data largely centered on misconduct, paternity,
forensic applications, and insurance and employment discrimination. Although
surrogate decision makers expressed that their loved ones would have interest in
return of results and being recontacted for future use, these interests were
secondary to confidentiality concerns. CONCLUSION: Respondents perceived genetic
and nongenetic data as comparable. Informed consent processes that provide clear
information regarding confidentiality protections, specimen handling, and
parameters for future use may enhance enrollment.Genet Med 2013:15(5):368-373.
PMID- 23154526
TI - Different cilia response to adenosine triphosphate or benzalkonium chloride
treatment in mouse nasal and tracheal culture.
AB - OBJECTIVES: Our purpose was to compare the ciliary function between the upper and
lower airway. METHODS: Basal ciliary beat frequency (CBF) and changes in CBF in
response to exogenous stimuli [adenosine triphosphate (ATP) or benzalkonium
chloride (BAC)] of primary cultured mouse nasal and tracheal epithelial cells
were quantified using digital microscopy combined with a beat-by-beat CBF
analysis. RESULTS: The basal CBF of the mouse tracheal culture was statistically
higher than the nasal culture. Adding 10 or 100 uM ATP caused an increase of CBF
in both mouse nasal and tracheal cultures; however, nasal culture induced a more
robust increase of CBF than tracheal culture. Treatment with 0.001% BAC increased
CBF within 2 min after treatment and then CBF gradually decreased; nasal and
tracheal culture manifested a similar change in CBF. With a concentration of
0.01%, BAC induced a rapid and time-dependent decrease of CBF in both mouse nasal
and tracheal cultures; however, tracheal culture showed a blunter response to
this ciliotoxic agent, with the ciliary beating duration time distinguishably
longer than in the nasal culture. CONCLUSION: The inherent ciliary and
physiological function is different in the upper and lower airway in mice.
PMID- 23154527
TI - Refining the diagnosis and prognostic categorization of acute myeloid leukemia
patients with an integrated use of cytogenetic and molecular studies.
AB - Significant progress in the understanding of the genetic basis of acute myeloid
leukemia (AML) has been made during the last 30 years. The aim of the present
study was to assess whether the detection of recurrent gene rearrangements by
fluorescent in situ hybridization (FISH) studies and NPM1 and FLT3 gene mutations
by molecular studies added clinically relevant information to the karyotype in
113 AML patients. Thus, FISH and molecular studies were found to add new
information in 22 and 55% of the patients, respectively, particularly in cases
with normal karyotype (NK) or when a cytogenetic analysis failed. Patients with
NK changed their genetic risk group to favorable in 27 and 29% of cases using
FISH and molecular biology studies, respectively. Our results demonstrate that
molecular biology and FISH studies provide relevant information in AML and should
be routinely performed.
PMID- 23154528
TI - Challenging false discovery rate: a partition test based on p values in human
case-control association studies.
AB - BACKGROUND/AIMS: We consider the situation that multiple genetic variants are
underlying a heritable trait and assume that each contributes to the trait only
to a small degree. The aim is to develop a statistical test for disease
association of these multiple variants. METHODS: We expect that p values
resulting from a genome-wide case-control association analysis will fall into two
classes: those reflecting true association and those occurring randomly in the
interval from 0 to 1. We develop a partition test to find the set of smallest p
values deviating most from the number of p values expected under randomness.
RESULTS: Power calculations demonstrate the superiority of our partition test
over conventional SNP-by-SNP analyses. Applications of the partition test to six
published datasets show that our test is particularly suitable when multiple SNPs
appear to contribute to a trait, and furnished more significant results than a
well-known procedure to estimate the false discovery rate. CONCLUSIONS: Our
partition test also furnishes an estimate of the number of functional SNPs
underlying disease and can be highly significant, while single-locus tests may be
far from significant.
PMID- 23154529
TI - 1,5-(H, RO, RS) shift/6pi-electrocyclic ring closure tandem processes on N
[(alpha-heterosubstituted)-2-tolyl]ketenimines: a case study of relative
migratory aptitudes and activating effects.
AB - A number of N-aryl ketenimines, substituted at the ortho position either with
different non-cyclic acetalic functions (acetals, monothioacetals, dithioacetals)
or with only one alkoxymethyl or (alkylthio)methyl group, have been prepared and
submitted to thermal treatment in toluene solution. Under smooth heating the
ketenimines bearing non-cyclic acetals converted into 3,4-dihydroquinolines
following two competitive tandem sequences that involve the alternative 1,5
migration of a hydride or alkoxy group as the first mechanistic step, followed by
subsequent 6pi electrocyclic ring closure. The heterocumulenes bearing acyclic
monothioacetal and dithioacetal functions converted via a unique consecutive
process involving the selective migration of the alkanethiolate group.
Ketenimines bearing only one ether or thioether group transformed exclusively by
the tandem sequence initiated by a 1,5 hydride shift. All these transformations
provided as final reaction products a variety of quinoline derivatives with a
range of substitution patterns. From these experiments the following order of
propensity to migration can be extracted: RS > RO > H. It was also possible to
estimate the following order of relative activating activities: RO > RS > H.
PMID- 23154530
TI - Central obesity and smoking are key modifiable risk factors for elevated C
reactive protein in Asian individuals who are not eligible for statin therapy.
AB - OBJECTIVE: Statin therapy reduces coronary heart disease (CHD) and mortality in
individuals with elevated C-reactive protein (CRP) but low-density lipoprotein
cholesterol below the threshold at which statin therapy is recommended. We
determined the proportion of individuals with elevated CRP in whom statin therapy
was not indicated, and examined predictors for elevated CRP in a multi-ethnic
Asian population. DESIGN: We studied 3404 participants (Chinese, Malays and Asian
Indians) without a history of hypercholesterolemia living in Singapore (mean
age+/-s.d.: 48.9+/-11.2 years). Eligibility for statin therapy was determined
based on the National Cholesterol Education Program (NCEP) Expert Panel on
Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult
Treatment Panel III (ATPIII)) guideline. CRP was measured by high-sensitivity
enzyme-linked immunosorbent assay method. CRP level greater than 2 mg l(-1) was
considered as elevated. RESULTS: Elevated CRP was found in 29.3% participants who
were not eligible for statin therapy (n=2974). Elevated CRP was more common in
females and amongst those of Malay or Asian-Indian ethnicity. Compared with
participants with low CRP, those with elevated CRP were shown to have higher
levels of obesity, blood pressure, triglyceride and insulin resistance (IR), but
lower high-density lipoprotein cholesterol levels (all Ps<0.001). After
multivariate analysis, gender (odds ratio (OR) 3.34 for females), ethnicity
(Malay OR 1.57, 95% confidence interval (CI) 1.25-1.96; Asian-Indian OR 1.97, 95%
CI 1.55-2.50), waist circumference (OR 1.06, 95% CI 1.05-1.07), smoking (OR 1.49,
95% CI 1.08-2.05) and IR (OR 1.14, 95% CI 1.07-1.22) were significant predictors
of CRP (all Ps--values<0.05). CONCLUSION: Routine measurement of CRP identifies a
substantial number of Asian individuals at risk of CHD in whom statin therapy is
not currently indicated, particularly in women and certain ethnic groups (Malays
and Asian Indians). Weight loss and smoking cessation are important measures to
reduce the proportion of individuals with elevated CRP.
PMID- 23154531
TI - Sensing applications of synthetic transport systems.
AB - This feature article offers a comprehensive account of a decade of research
devoted to the combination of the grand sensing principles with synthetic
transport systems that act in lipid bilayers. Differential sensing, that is
pattern generation and pattern recognition, is exemplified with an artificial
nose. The aptamer version of immunosensing is realized with sticky-end polymers
of DNA double helices for both signal generation and signal transduction.
Biosensing, that is the use of enzymes for signal generation, is exemplified
first with an artificial tongue and then expanded to analytes such as
cholesterol, phytate or polyphenols. Enjoyable also for the general reader, we
hope that this account will inspire supramolecular organic as well as analytical,
physical and biological chemists.
PMID- 23154532
TI - Long term effects of the implantation of Wharton's jelly-derived mesenchymal stem
cells from the umbilical cord for newly-onset type 1 diabetes mellitus.
AB - Type 1 diabetes mellitus (T1DM) is an autoimmune disorder resulted from T cell
mediated destruction of pancreatic beta-cells, how to regenerate beta-cells and
prevent the autoimmune destruction of remnant and neogenetic beta-cells is a
tough problem. Immunomodulatory propertity of mesenchymal stem cell make it
illuminated to overcome it. We assessed the long-term effects of the implantation
of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) from the umbilical
cord for Newly-onset T1DM. Twenty-nine patients with newly onset T1DM were
randomly divided into two groups, patients in group I were treated with WJ-MSCs
and patients in group II were treated with normal saline based on insulin
intensive therapy. Patients were followed-up after the operation at monthly
intervals for the first 3 months and thereafter every 3 months for the next 21
months, the occurrence of any side effects and results of laboratory examinations
were evaluated. There were no reported acute or chronic side effects in group I
compared with group II, both the HbA1c and C peptide in group I patients were
significantly better than either pretherapy values or group II patients during
the follow-up period. These data suggested that the implantation of WJ-MSCs for
the treatment of newly-onset T1DM is safe and effective. This therapy can restore
the function of islet beta cells in a longer time, although precise mechanisms
are unknown, the implantation of WJ-MSCs is expected to be an effective strategy
for treatment of type1 diabetes.
PMID- 23154533
TI - The onset of antineutrophil cytoplasmic antibody-associated vasculitis
immediately after methimazole was switched to propylthiouracil in a woman with
Graves' disease who wished to become pregnant.
AB - Propylthiouracil (PTU) is recommended as a first-line antithyroid drug (ATD)
during first trimester organogenesis in pregnancy because recent evidence
suggests that methimazole (MMI) may be associated with congenital anomalies.
However, PTU more commonly causes myeloperoxidase (MPO)-antineutrophil
cytoplasmic antibody (ANCA)-associated vasculitis, which usually occurs during
prolonged treatment, compared with MMI. We report a case of MPO-ANCA-associated
vasculitis in a 35-year-old woman with Graves'disease. Although her thyroid
function could be maintained euthyroid by MMI, her ATD was switched to PTU
because she wished to become pregnant. The patient presented with flu-like
symptoms 8 days after starting PTU and developed hemoptysis and dyspnea at 22
days. Her MPO-ANCA titer was 21 ELISA units (EUs) before PTU treatment but
increased to 259 EUs at 22 days after PTU treatment. Her clinical condition
improved with the discontinuation of PTU and with immunosuppressive therapy. This
case indicated that MPO-ANCA vasculitis occurred within several weeks after the
initiation of PTU and that this side effect could be caused by the change from
MMI to PTU. Thus, our clinical observation suggests that patients treated with
PTU should be carefully monitored for MPO-ANCA titers and variable manifestations
of MPO-ANCA-associated vasculitis regardless of the period of administration.
PMID- 23154534
TI - One divinyl reductase reduces the 8-vinyl groups in various intermediates of
chlorophyll biosynthesis in a given higher plant species, but the isozyme differs
between species.
AB - Divinyl reductase (DVR) converts 8-vinyl groups on various chlorophyll
intermediates to ethyl groups, which is indispensable for chlorophyll
biosynthesis. To date, five DVR activities have been detected, but adequate
evidence of enzymatic assays using purified or recombinant DVR proteins has not
been demonstrated, and it is unclear whether one or multiple enzymes catalyze
these activities. In this study, we systematically carried out enzymatic assays
using four recombinant DVR proteins and five divinyl substrates and then
investigated the in vivo accumulation of various chlorophyll intermediates in
rice (Oryza sativa), maize (Zea mays), and cucumber (Cucumis sativus). The
results demonstrated that both rice and maize DVR proteins can convert all of the
five divinyl substrates to corresponding monovinyl compounds, while both cucumber
and Arabidopsis (Arabidopsis thaliana) DVR proteins can convert three of them.
Meanwhile, the OsDVR (Os03g22780)-inactivated 824ys mutant of rice exclusively
accumulated divinyl chlorophylls in its various organs during different
developmental stages. Collectively, we conclude that a single DVR with broad
substrate specificity is responsible for reducing the 8-vinyl groups of various
chlorophyll intermediates in higher plants, but DVR proteins from different
species have diverse and differing substrate preferences, although they are
homologous.
PMID- 23154535
TI - Regulation of miR399f transcription by AtMYB2 affects phosphate starvation
responses in Arabidopsis.
AB - Although a role for microRNA399 (miR399) in plant responses to phosphate (Pi)
starvation has been indicated, the regulatory mechanism underlying miR399 gene
expression is not clear. Here, we report that AtMYB2 functions as a direct
transcriptional activator for miR399 in Arabidopsis (Arabidopsis thaliana) Pi
starvation signaling. Compared with untransformed control plants, transgenic
plants constitutively overexpressing AtMYB2 showed increased miR399f expression
and tissue Pi contents under high Pi growth and exhibited elevated expression of
a subset of Pi starvation-induced genes. Pi starvation-induced root architectural
changes were more exaggerated in AtMYB2-overexpressing transgenic plants compared
with the wild type. AtMYB2 directly binds to a MYB-binding site in the miR399f
promoter in vitro, as well as in vivo, and stimulates miR399f promoter activity
in Arabidopsis protoplasts. Transcription of AtMYB2 itself is induced in response
to Pi deficiency, and the tissue expression patterns of miR399f and AtMYB2 are
similar. Both genes are expressed mainly in vascular tissues of cotyledons and in
roots. Our results suggest that AtMYB2 regulates plant responses to Pi starvation
by regulating the expression of the miR399 gene.
PMID- 23154537
TI - Cubic regression-based degree of correction predicts the performance of whole
bisulfitome amplified DNA methylation analysis.
AB - Epigenetic mechanisms, including DNA methylation, are important determinants in
development and disease. There is a need for technologies capable of detecting
small variations in methylation levels in an accurate and reproducible manner,
even if only limited amounts of DNA are available (which is the case in many
studies in humans). Quantitative methylation analysis of minute DNA amounts after
whole bisulfitome amplification (qMAMBA) has been proposed as an alternative, but
this technique has not been adequately standardized and no comparative study
against conventional methods has been performed, that includes a wide range of
methylation percentages and different target assays. We designed an experiment to
compare the performance of qMAMBA and bisulfite-treated genomic (non-amplified)
DNA pyrosequencing. Reactions were performed in duplicate for each technique in
eight different target genes, using nine artificially constructed DNA samples
with methylation levels ranging between 0% and 100% with intervals of 12.5%.
Cubic polynomial curves were plotted from the experimental results and the real
methylation values and the resulting equation was used to estimate new corrected
data points. The use of the cubic regression-based correction benefits the
accuracy and the power of discrimination in methylation studies. Additionally,
dispersion of the new estimated data around a y = x line (R ( 2) ) served to fix
a cutoff that can discriminate, with a single 9-point curve experiment, whether
whole bisulfitome amplification and subsequent qMAMBA can produce accurate
methylation results. Finally, even with an optimized reagent kit, DNA samples
subjected to whole bisulfitome amplification enhance the preferential
amplification of unmethylated alleles, and subtle changes in methylation levels
cannot be detected confidently.
PMID- 23154536
TI - Chlamydomonas reinhardtii chloroplasts contain a homodimeric pyruvate:ferredoxin
oxidoreductase that functions with FDX1.
AB - Eukaryotic algae have long been known to live in anoxic environments, but
interest in their anaerobic energy metabolism has only recently gained momentum,
largely due to their utility in biofuel production. Chlamydomonas reinhardtii
figures remarkably in this respect, because it efficiently produces hydrogen and
its genome harbors many genes for anaerobic metabolic routes. Central to
anaerobic energy metabolism in many unicellular eukaryotes (protists) is
pyruvate:ferredoxin oxidoreductase (PFO), which decarboxylates pyruvate and forms
acetyl-coenzyme A with concomitant reduction of low-potential ferredoxins or
flavodoxins. Here, we report the biochemical properties of the homodimeric PFO of
C. reinhardtii expressed in Escherichia coli. Electron paramagnetic resonance
spectroscopy of the recombinant enzyme (Cr-rPFO) showed three distinct [4Fe-4S]
iron-sulfur clusters and a thiamine pyrophosphate radical upon reduction by
pyruvate. Purified Cr-rPFO exhibits a specific decarboxylase activity of 12 umol
pyruvate min-1 mg-1 protein using benzyl viologen as electron acceptor. Despite
the fact that the enzyme is very oxygen sensitive, it localizes to the
chloroplast. Among the six known chloroplast ferredoxins (FDX1-FDX6) in C.
reinhardtii, FDX1 and FDX2 were the most efficient electron acceptors from Cr
rPFO, with comparable apparent K(m) values of approximately 4 um. As revealed by
immunoblotting, anaerobic conditions that lead to the induction of CrPFO did not
increase levels of either FDX1 or FDX2. FDX1, being by far the most abundant
ferredoxin, is thus likely the partner of PFO in C. reinhardtii. This finding
postulates a direct link between CrPFO and hydrogenase and provides new
opportunities to better study and engineer hydrogen production in this protist.
PMID- 23154538
TI - Pyruvate kinase is a dosage-dependent regulator of cellular amino acid
homeostasis.
AB - The glycolytic enzyme pyruvate kinase (PK) is required for cancer development,
and has been implicated in the metabolic transition from oxidative to
fermentative metabolism, the Warburg effect. However, the global metabolic
response that follows changes in PK activity is not yet fully understood. Using
shotgun proteomics, we identified 31 yeast proteins that were regulated in a PK
dependent manner. Selective reaction monitoring confirmed that their expression
was dependent on PK isoform, level and activity. Most of the PK targets were
amino acid metabolizing enzymes or factors of protein translation, indicating
that PK plays a global regulatory role in biosynthethic amino acid metabolism.
Indeed, we found strongly altered amino acid profiles when PK levels were
changed. Low PK levels increased the cellular glutamine and glutamate
concentrations, but decreased the levels of seven amino acids including serine
and histidine. To test for evolutionary conservation of this PK function, we
quantified orthologues of the identified PK targets in thyroid follicular
adenoma, a tumor characterized by high PK levels and low respiratory activity.
Aminopeptidase AAP-1 and serine hydroxymethyltransferase SHMT1 both showed PKM2-
concentration dependence, and were upregulated in the tumor. Thus, PK expression
levels and activity were important for maintaining cellular amino acid
homeostasis. Mediating between energy production, ROS clearance and amino acid
biosynthesis, PK thus plays a central regulatory role in the metabolism of
proliferating cells.
PMID- 23154540
TI - Comparison of NT-proBNP levels in hemodialysis versus peritoneal dialysis
patients.
AB - BACKGROUND: Plasma N-terminal fragment of pro brain natriuretic peptide (NT
proBNP) concentration is elevated in cardiovascular diseases such as congestive
heart failure, where increased levels of NT-proBNP indicate cardiac dysfunction,
hypervolemia, and higher risk of hospitalization and death. These associations
apply also to patients with severe impairment of kidney function. Little is known
about diferences in plasma level of NT-proBNP in patients receiving hemodialysis
(HD) versus those receiving continuous ambulatory peritoneal dialysis (CAPD).
AIM: To evaluate differences in plasma NT-proBNP concentration between HD and
CAPD patients. METHODS: Plasma NT-proBNP concentration was prospectively measured
in consecutive patients receiving either HD or CAPD at our hospital center. All
other standard clinical parameters were recorded. The correlation between plasma
NT-proBNP concentration and the type of dialysis was then examined. RESULTS: We
studied 99 consecutive patients on HD (age 62 +/- 15 years, 66% male) and 18
consecutive patients on CAPD (age 56 +/- 18 years, 67% male). Both groups had
similar baseline characteristics including duration of dialysis, left ventricular
function and mass, and cardiothoracic ratio. Significantly more patients on HD
had abnormal NT-proBNP levels compared to patients on CAPD (97% vs 44%;
P<0.0001), and this difference remained highly significant when using various NT
proBNP cut off values. A subgroup analysis revealed that the lower NT-proBNP
levels of CAPD patients are most pronounced in patients with preserved left
ventricular ejection function. As expected, NT-proBNP levels correlated
negatively with left ventricular function and positively with cardiothoracic
ratio, and this applied to both HD and CAPD groups. CONCLUSION: The lower
concentration of NT-proBNP in patients on CAPD compared to those on HD suggests
that CAPD produces lesser hemodynamic stress, especially in patients with
preserved left ventricular systolic function. Even though increased NT-proBNP
levels have been shown to predict increased morbidity and mortality, further
studies are necessary to assess the long term benefit of CAPD compared to HD.
PMID- 23154539
TI - Small regulatory RNAs controlled by genomic imprinting and their contribution to
human disease.
AB - More than a hundred protein-coding genes are controlled by genomic imprinting in
humans. These atypical genes are organized in chromosomal domains, each of which
is controlled by a differentially methylated "imprinting control region" (ICR).
How ICRs mediate the parental allele-specific expression of close-by genes is now
becoming understood. At several imprinted domains, this epigenetic mechanism
involves the action of long non-coding RNAs. It is less well appreciated that
imprinted gene domains also transcribe hundreds of microRNA and small nucleolar
RNA genes and that these represent the densest clusters of small RNA genes in
mammalian genomes. The evolutionary reasons for this remarkable enrichment of
small regulatory RNAs at imprinted domains remain unclear. However, recent
studies show that imprinted small RNAs modulate specific functions in development
and metabolism and also are frequently perturbed in cancer. Here, we review our
current understanding of imprinted small RNAs in the human genome and discuss how
perturbation of their expression contributes to disease.
PMID- 23154541
TI - Endovascular brain intervention and mapping in a dog experimental model using
magnetically-guided micro-catheter technology.
AB - AIM: Despite the substantial progress that has been achieved in interventional
cardiology and cardiac electrophysiology, endovascular intervention for the
diagnosis and treatment of central nervous system (CNS) disorders such as stroke,
epilepsy and CNS malignancy is still limited, particularly due to highly tortuous
nature of the cerebral arterial and venous system. Existing interventional
devices and techniques enable only limited and complicated access especially into
intra-cerebral vessels. The aim of this study was to develop a micro-catheter
magnetically-guided technology specifically designed for endovascular
intervention and mapping in deep CNS vascular structures. METHODS: Mapping of
electrical brain activity was performed via the venous system on an animal dog
model with the support of the NIOBE II system. RESULTS: A novel micro-catheter
specially designed for endovascular interventions in the CNS, with the support of
the NIOBE II technology, was able to reach safely deep intra-cerebral venous
structures and map the electrical activity there. Such structures are not
currently accessible using standard catheters. CONCLUSION: This is the first
study demonstrating successful use of a new micro-catheter in combination with
NIOBE II technology for endovascular intervention in the brain.
PMID- 23154542
TI - EGFR gene mutations: is it prognostic or predictive in surgically resected lung
cancer?
PMID- 23154543
TI - The achilles' heel of lung cancer resection in the United States.
PMID- 23154544
TI - Interpretation of PET scans: do not take SUVs at face value.
PMID- 23154545
TI - G-protein coupled receptor family C, group 5, member A (GPRC5A) expression is
decreased in the adjacent field and normal bronchial epithelia of patients with
chronic obstructive pulmonary disease and non-small-cell lung cancer.
AB - INTRODUCTION: Understanding oncogenes and tumor suppressor genes expression
patterns is essential for characterizing lung cancer pathogenesis. We have
previously demonstrated that mGprc5a/hGPRC5A is a lung-specific tumor suppressor
evidenced by inflammation-mediated tumorigenesis in Gprc5a-knockout mice. The
implication of GPRC5A in human lung cancer pathogenesis, including that
associated with inflammatory chronic obstructive pulmonary disease (COPD), a risk
factor for the malignancy, remains elusive. METHODS: We sought to examine GPRC5A
immunohistochemical expression in histologically normal bronchial epithelia (NBE)
from lung disease-free never- and ever-smokers (n = 13 and n = 18, respectively),
from COPD patients with (n = 26) and without cancer (n = 24) and in non-small
cell lung cancers (NSCLCs) (n = 474). Quantitative assessment of GPRC5A
transcript expression in airways (n = 6), adjacent NBEs (n = 29) and
corresponding tumors (n = 6) from 6 NSCLC patients was also performed. RESULTS:
GPRC5A immunohistochemical expression was significantly lower in tumors compared
to uninvolved NBE (p < 0.0001) and was positively associated with adenocarcinoma
histology (p < 0.001). GPRC5A airway expression was highest in lung disease-free
NBE, decreased and intermediate in NBE of cancer-free COPD patients (p = 0.004)
and further attenuated and lowest in epithelia of COPD patients with
adenocarcinoma and SCC (p < 0.0001). Furthermore, GPRC5A mRNA was significantly
decreased in NSCLCs and corre sponding NBE compared to uninvolved normal lung (p
= 0.03). CONCLUSIONS: Our findings highlight decreased GPRC5A expression in the
field cancerization of NSCLC, including that associated with lung inflammation.
Assessment of the use of GPRC5A expression as a risk factor for NSCLC development
in COPD patients is warranted.
PMID- 23154546
TI - A pilot characterization of human lung NSCLC by protein pathway activation
mapping.
AB - BACKGROUND: An understanding of the activated protein signaling architecture in
non-small-cell lung cancer (NSCLC) is of critical importance to the development
of new therapeutic approaches and identification of predictive and prognostic
biomarkers for patient stratification. METHODS: We used reverse-phase protein
microarrays to map the activated protein signaling networks of 47 NSCLC tumors,
28 of which were node negative, which were subjected to tumor cellular enrichment
using laser capture microdissection. The phosphorylation/cleavage levels of 111
key signaling proteins and total levels of 17 proteins were measured for
broadscale signaling analysis. RESULTS: Pathway activation mapping of NSCLC
revealed distinct subgroups composed of epidermal growth factor receptor (ERBB1),
v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (ERBB2), v-erb-b2
erythroblastic leukemia viral oncogene homolog 3 (ERBB3), v-erb-a erythroblastic
leukemia viral oncogene homolog 4 (ERBB4), v-akt murine thymoma viral oncogene
homolog 1- mammalian target of rapamycin (AKT-mTOR), protein kinase, AMP
activated, alpha 2 catalytic subunit (AMPK), and autophagy-related signaling,
along with transforming growth factor-beta-signaling protein 1 (SMAD), insulin
line growth factor receptor (IGFR), rearranged during transfection proto-oncogene
(RET), and activated CDC42-associated kinase (ACK) activation. Investigation of
epidermal growth factor receptor (EGFR)-driven signaling identified a unique
cohort of tumors with low EGFR protein expression yet high relative levels of
phosphorylated EGFR and high EGFR total protein with low relative levels of
phosphorylation. Last, mapping analysis of patients with NSCLC with N0 disease
revealed a pilot pathway activation signature composed of linked epidermal growth
factor receptor family (HER)-AMPK-AKT-mTOR signaling network along with focal
adhesion kinase- LIM domain kinase-1 (FAK-LIMK) and janus kinase (JAK)-signal
transducers and activators of transcription (STAT) pathways that correlated with
short-term survival and aggressive disease. CONCLUSIONS: Functional protein
pathway activation mapping of NSCLC reveals distinct activation subgroups that
are underpinned by important therapeutic targets and that patients with early
stage node negative disease and poor prognosis may be identified by activation of
defined, biochemically linked protein signaling events. Such findings, if
confirmed in larger study sets, could help select and stratify patients for
personalized targeted therapies.
PMID- 23154547
TI - The introduction of systematic genomic testing for patients with non-small-cell
lung cancer.
AB - BACKGROUND: Genomic testing to identify driver mutations that enable targeted
therapy is emerging for patients with non-small-cell lung cancer (NSCLC). We
report the implementation of systematic prospective genotyping for somatic
alterations in BRAF, PIK3CA, HER2, and ALK, in addition to EGFR and KRAS, in
NSCLC patients at the Dana-Farber Cancer Institute. METHODS: Patients with NSCLC
were prospectively referred by their providers for clinical genotyping. Formalin
fixed, paraffin embedded tumor samples were analyzed by Sanger sequencing for
mutations in selected exons of EGFR, KRAS, BRAF, PIK3CA, and HER2. ALK
rearrangements were detected by fluorescence in situ hybridization or
immunohistochemistry. RESULTS: Between July 1, 2009 and August 1, 2010, 427
specimens from 419 patients were referred for genomic characterization; 344 (81%)
specimens were successfully genotyped with a median turnaround time of 31 days
(range, 9-155). Of the 344 specimens, 185 (54%) had at least one identifiable
somatic alteration (KRAS: 24%, EGFR: 17%, ALK: 5%, BRAF: 5%, HER2: 4%, PIK3CA:
2%). As of August 1, 2011, 63 of 288 advanced NSCLC patients (22%) had received
molecularly targeted therapy based on their genotypic results, including 34 of 42
patients (81%) with EGFR mutations, 12 of 15 (80%) with ALK rearrangements, and
17 of 95 (18%) with KRAS, BRAF, or HER2 mutations. CONCLUSIONS: Large-scale
testing for somatic alterations in EGFR, KRAS, BRAF, PIK3CA, HER2, and ALK is
feasible and impacts therapeutic decisions. As the repertoire for personalized
therapies expands in lung cancer and other malignancies, there is a need to
develop new genomics technologies that can generate a comprehensive genetic
profile of tumor specimens in a time- and cost-effective manner.
PMID- 23154548
TI - FGFR1 amplification in squamous cell carcinoma of the lung.
AB - INTRODUCTION: Amplification of fibroblast growth factor receptor 1 (FGFR1) has
been reported in squamous cell lung carcinoma and may be a molecular target for
therapy. Little is known, however, about the clinical and demographic correlates
of FGFR1 amplification. METHODS: The study is an Institutional Review Board
approved retrospective analysis of 226 patients with squamous cell lung cancer
seen at the Massachusetts General Hospital from 2005 to 2011. Clinical and
demographic characteristics of all patients were obtained, as well as treatment
details including surgery, radiation, and chemotherapy, and overall survival.
fluorescence in situ hybridization was performed for FGFR1 on formalin-fixed
paraffin-embedded tumor tissue. Clinical genotyping results were also reviewed
where available. RESULTS: Thirty-seven of 226 patients (16%) with squamous cell
lung cancer were found positive for amplification using a definition of
amplification of a gene to copy number control ratio of 2.2 or higher. FGFR1
amplification status was not associated with age, sex, stage, histologic subtype
within squamous cell, smoking history, or pack-years of smoking. We found no
significant difference in overall survival by FGFR1 amplification status as a
whole; in the advanced stage subset, our findings are inconclusive because of the
small sample size. CONCLUSION: FGFR1 amplification was found in 16% of a clinical
cohort of squamous cell lung cancer patients. The lack of any specific
clinicodemographic features that correlates with FGFR1 amplification suggests
that all squamous cell patients should be tested for this genomic change.
PMID- 23154549
TI - Can determination of circulating endothelial cells and serum caspase-cleaved CK18
predict for response and survival in patients with advanced non-small-cell lung
cancer receiving endostatin and paclitaxel-carboplatin chemotherapy? a
retrospective study.
AB - INTRODUCTION: Early prediction of the efficacy of a combination of an
antiangiogenic drug with cytotoxic chemotherapy is a significant challenge. In
that regard, circulating endothelial cells (CECs) and cytokeratins (CKs) seem to
reflect their roles in both tumor angiogenesis and tumor cell death. METHODS:
Patients with advanced, previously untreated non-small-cell lung cancer were
randomly assigned to an endostatin treatment group (paclitaxel + carboplatin +
endostatin) and a control group (paclitaxel + carboplatin + placebo). A total of
122 patients were evaluated, of whom 107 had measurements of blood CECs, CK8,
caspase-cleaved CK18 (ccCK18), and uncleaved CK18 (CK18) before and at weeks 3
and 6 of treatment, respectively. RESULTS: Higher baseline CECs in patients with
a tumor response (partial remission + stable disease, p = 0.002 for the entire
group; p = 0.000 for the treatment group) were observed. The number of CECs
decreased significantly after endostatin treatment (p = 0.000), whereas CK levels
increased. Increased levels of ccCK18 and CK18, but not CK8, reached significance
(p = 0.001 and p = 0.048, respectively) when compared with the baseline. Tumor
response showed a strong correlation with reduction of CECs (p = 0.000) and
increase of ccCK18 (p = 0.040) after endostatin therapy. Cutoff values of changes
of CECs and ccCK18 for prediction of survival were 0.58/MUl and 19.6 ng/ml,
respectively. Reduction of CECs and increase of ccCK18 significantly correlated
with longer median survival (p = 0.013 and p = 0.016 for progression-free
survival; p = 0.009 and p = 0.012 for overall survival, respectively).
CONCLUSIONS: CECs and CKs could be biomarkers for selecting patients with non
small-cell lung cancer who will benefit from treatment with endostatin in
combination with paclitaxel plus carboplatin.
PMID- 23154550
TI - Prognostic impact of CD204-positive macrophages in lung squamous cell carcinoma:
possible contribution of Cd204-positive macrophages to the tumor-promoting
microenvironment.
AB - INTRODUCTION: Tumor-associated macrophages (TAMs) are recruited into cancer
induced stroma and produce a specific microenvironment for cancer progression.
CD204 (+) TAMs are reportedly related to tumor progression and clinical outcome
in some tumors. The aim of this study was to clarify the correlation between
CD204 (+) TAMs and the clinicopathological features of lung squamous cell
carcinoma. METHODS: We investigated the relationships between the numbers of
CD204 (+) TAMs and clinicopathological factors, microvessel density, and the
numbers of Foxp3 (+) lymphocytes in 208 consecutively resected cases. We also
examined the relationships between the numbers of CD204 (+) TAMs and the
expression levels of cytokines involved in the migration and differentiation of
CD204 (+) TAMs. RESULTS: A high number of CD204 (+) TAMs in the stroma was
significantly correlated with an advanced p-stage, T factor, N factor, and the
presence of vascular and pleural invasion. A high number of CD204 (+) TAMs in the
stroma was also a significant prognostic factor for all p-stages and p-stage I.
Moreover, the numbers of CD204 (+) TAMs were correlated with the microvessel
density and the numbers of Foxp3 (+) lymphocytes. A high number of CD204 (+) TAMs
was strongly correlated with the tissue expression level of monocyte
chemoattractant protein-1. CD204 (+) TAMs were shown to be significant
independent prognostic factors in a multivariate analysis. CONCLUSIONS: CD204 (+)
TAMs were an independent prognostic factor in lung squamous cell carcinoma. CD204
(+) TAMs, along with other tumor-promoting stromal cells such as regulatory T
cells and endothelial cells, may create tumor-promoting microenvironments.
PMID- 23154551
TI - Mediastinal lymph node examination and survival in resected early-stage non-small
cell lung cancer in the surveillance, epidemiology, and end results database.
AB - BACKGROUND: Pathologic nodal stage is the key prognostic factor in resectable non
small-cell lung cancer (NSCLC). Mediastinal lymph node (MLN) metastasis connotes
a poor prognosis. Yet, some NSCLC resections exclude MLN examination. METHODS: We
analyzed U.S. Surveillance, Epidemiology, and End Results program data from 1998
to 2002 to quantify the long-term survival impact of failure to examine MLN in
resected NSCLC. We used Kaplan-Meier methods to compare the unadjusted survival
difference between patients with, and without, MLN examination, and Cox
proportional hazards and competing risk models to serially adjust for the impact
of risk factors on survival differences. RESULTS: Sixty-two percent of patients
with pathologic N0 or N1 NSCLC had no MLN examined. Overall 5-year survival rates
were 52% for those with, versus 47% for those without, MLN examination; lung
cancer-specific survival rates were 63% versus 58% respectively (p < 0.001);
nonlung cancer mortality was identical between cohorts. Adjusting for potential
confounders, MLN examination was associated with a 7% reduction in all-cause
mortality (hazard ratio, 0.93; confidence interval, 0.88-0.97; p = 0.002), and
11% reduction in lung cancer-specific mortality (hazard ratio, 0.89; 95%
confidence interval, 0.84-0.95; p < 0.001) rates. The excess risk in 1 year's
cohort of U.S. lung resections was 3150 lives over 5 years. CONCLUSIONS: Failure
to examine MLN was a common practice in MLN-negative NSCLC resections, which
significantly impaired long-term survival. Efforts to understand the etiology of
this quality gap, and measures to eliminate it, are warranted.
PMID- 23154553
TI - Distinct clinical course of EGFR-mutant resected lung cancers: results of testing
of 1118 surgical specimens and effects of adjuvant gefitinib and erlotinib.
AB - BACKGROUND: EGFR and KRAS mutations are mutually exclusive and predict outcomes
with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)
treatment in patients with stage IV lung cancers. The clinical significance of
these mutations in patients with resected stage I-III lung cancers is unclear.
METHODS: At our institution, resection specimens from patients with stage I-III
lung adenocarcinomas are tested for the presence of EGFR or KRAS mutations during
routine pathology analysis such that the results are available before
consideration of adjuvant therapy. In a cohort of 1118 patients tested over 8
years, overall survival was analyzed using multivariate analysis to control for
potential confounders, including age, sex, stage, and smoking history. The impact
of adjuvant erlotinib or gefitinib was examined in an independent data set of
patients exclusively with EGFR mutation, in which date of recurrence was
recorded. RESULTS: In the overall population, we identified 227 KRAS (25%) and
222 EGFR (20%) mutations. Patients with EGFR-mutant lung cancers had a lower risk
of death compared with those without EGFR mutations, overall survival (OS) HR
0.51 (95% confidence interval [CI]: 0.34-0.76, p < 0.001). Patients with KRAS
mutant lung cancers had similar outcomes compared with individuals with KRAS wild
type tumors, OS HR 1.17 (95% CI: 0.87-1.57, p = 0.30). A separate data set
includes only patients with EGFR-mutant lung cancers identified over 10 years (n
= 286). In patients with resected lung cancers and EGFR mutation, treatment with
adjuvant erlotinib or gefitinib was associated with a lower risk of recurrence or
death, disease-free survival HR 0.43 (95% CI: 0.26-0.72, p = 0.001), and a trend
toward improved OS. CONCLUSIONS: Patients with resected stage I-III lung cancers
and EGFR mutation have a lower risk of death compared with patients without EGFR
mutation. This may be because of treatment with EGFR TKIs. Patients with, and
without KRAS mutation have similar OS. These data support reflex testing of
resected lung adenocarcinomas for EGFR mutation to provide prognostic information
and identify patients for enrollment on prospective clinical trials of adjuvant
EGFR TKIs.
PMID- 23154554
TI - Overall survival improvement in patients with lung cancer and bone metastases
treated with denosumab versus zoledronic acid: subgroup analysis from a
randomized phase 3 study.
AB - INTRODUCTION: Denosumab, a fully human anti-RANKL monoclonal antibody, reduces
the incidence of skeletal-related events in patients with bone metastases from
solid tumors. We present survival data for the subset of patients with lung
cancer, participating in the phase 3 trial of denosumab versus zoledronic acid
(ZA) in the treatment of bone metastases from solid tumors (except breast or
prostate) or multiple myeloma. METHODS: Patients were randomized 1:1 to receive
monthly subcutaneous denosumab 120 mg or intravenous ZA 4 mg. An exploratory
analysis, using Kaplan-Meier estimates and proportional hazards models, was
performed for overall survival among patients with non-small-cell lung cancer
(NSCLC) and SCLC. RESULTS: Denosumab was associated with improved median overall
survival versus ZA in 811 patients with any lung cancer (8.9 versus 7.7 months;
hazard ratio [HR] 0.80) and in 702 patients with NSCLC (9.5 versus 8.0 months; HR
0.78) (p = 0.01, each comparison). Further analysis of NSCLC by histological type
showed a median survival of 8.6 months for denosumab versus 6.4 months for ZA in
patients with squamous cell carcinoma (HR 0.68; p = 0.035). Incidence of overall
adverse events was balanced between treatment groups; serious adverse events
occurred in 66.0% of denosumab-treated patients and 72.9% of ZA-treated patients.
Cumulative incidence of osteonecrosis of the jaw was similar between groups (0.7%
denosumab versus 0.8% ZA). Hypocalcemia rates were 8.6% with denosumab and 3.8%
with ZA. CONCLUSION: In this exploratory analysis, denosumab was associated with
improved overall survival compared with ZA, in patients with metastatic lung
cancer.
PMID- 23154552
TI - Local ablative therapy of oligoprogressive disease prolongs disease control by
tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer.
AB - INTRODUCTION: Many patients with oncogene-driven non-small-cell lung cancer
(NSCLC) treated with tyrosine kinase inhibitors experience limited sites of
disease progression. This study investigated retrospectively the benefits of
local ablative therapy (LAT) to central nervous system (CNS) and/or limited
systemic disease progression and continuation of crizotinib or erlotinib in
patients with metastatic ALK gene rearrangement (ALK+) or EGFR-mutant (EGFR-MT)
NSCLC, respectively. METHODS: Patients with metastatic ALK+ NSCLC treated with
crizotinib (n = 38) and EGFR-MT NSCLC treated with erlotinib (n = 27) were
identified at a single institution. Initial response to the respective kinase
inhibitors, median progression-free survival (PFS1), and site of first
progression were recorded. A subset of patients with either nonleptomeningeal CNS
and/or four sites or fewer of extra-CNS progression (oligoprogressive disease)
suitable for LAT received either radiation or surgery to these sites and
continued on the same tyrosine kinase inhibitors. The subsequent median
progression-free survival from the time of first progression (PFS2) and pattern
of progression were recorded. RESULTS: Median progression-free survival in ALK+
patients on crizotinib was 9.0 months, and 13.8 months for EGFR-MT patients on
erlotinib. Twenty-five of 51 patients (49%) who progressed were deemed suitable
for local therapy (15 ALK+, 10 EGFR-MT; 24 with radiotherapy, one with surgery)
and continuation of the same targeted therapy. Post-LAT, 19 of 25 patients
progressed again, with median PFS2 of 6.2 months. DISCUSSION: Oncogene-addicted
NSCLC with CNS and/or limited systemic disease progression (oligoprogressive
disease) on relevant targeted therapies is often suitable for LAT and
continuation of the targeted agent, and is associated with more than 6 months of
additional disease control.
PMID- 23154555
TI - Quality of life analysis of TORCH, a randomized trial testing first-line
erlotinib followed by second-line cisplatin/gemcitabine chemotherapy in advanced
non-small-cell lung cancer.
AB - INTRODUCTION: The TORCH (Tarceva or Chemotherapy) trial randomized patients with
advanced non-small-cell lung cancer to first-line erlotinib followed by second
line cisplatin/gemcitabine versus. standard inverse sequence. The trial, designed
to test noninferiority in overall survival, was stopped at interim analysis
because of inferior survival in the experimental arm. Quality of life (QoL), a
secondary outcome, is reported here. METHODS: QoL was assessed at baseline and
every 3 weeks during first-line, using European Organization for Research and
Treatment of Cancer Quality of Life Questionnaire - Core 30 and QLQ-lung cancer
specific module (LC13). Mean changes from baseline within arms were reported. QoL
response and time-to-deterioration of QoL using a competing-risk approach were
compared between treatment arms. RESULTS: Six hundred and thirty patients (83%)
completed baseline questionnaires. Compliance was affected by differential
treatment efficacy, but was similar between arms for patients without progression
or death. Significant differences in QoL responses were observed favoring
chemotherapy for pain, sleeping, dyspnea, diarrhea, and favoring erlotinib for
vomiting, constipation, sore mouth, and alopecia. In the small subset of patients
with EGFR-mutated tumors, all selected items (global QoL, physical functioning,
cough, dyspnea and pain) improved, whereas worsening or no change was observed in
wild-type patients. Improvement was particularly evident in the first-line
erlotinib arm as for global QoL and physical functioning. CONCLUSIONS: QoL was
impacted by differential toxicity and efficacy between arms. Functional domains
and global QoL did not differ, although some symptoms were better controlled with
chemotherapy in unselected non-small-cell lung cancer patients.
PMID- 23154556
TI - E1B-55 kDa-defective adenoviruses activate p53 in mesothelioma and enhance
cytotoxicity of anticancer agents.
AB - INTRODUCTION: Genetic characterization of malignant mesothelioma shows a
homozygous deletion of the INK4A/ARF locus, which results in inactivation of the
p53 pathways. METHODS: We examined possible antitumor effects of adenoviruses
with a deletion of the E1B-55kD gene (Ad-delE1B55) on mesothelioma and
investigated combinatory actions with the first-line chemotherapeutic agents.
RESULTS: Ad-delE1B55 produced cytotoxicity on mesothelioma cells, which was
associated with p53 phosphorylation, pRb dephosphorylation, and cleavage of
caspases. Ad-delE1B55-infected cells displayed hyperploidy at the cell-cycle
analysis and showed enlarged nuclear configurations. Combination of Ad-delE1B55
plus cisplatin or pemetrexed produced antitumor effects in vitro. Furthermore, Ad
delE1B55 and cisplatin showed combinatory effects in an orthotopic animal model.
CONCLUSIONS: Cell death caused by Ad-delE1B55 is attributable to cell-cycle
arrest at M-phase checkpoint followed by activated apoptotic pathways, and
combination of the first-line chemotherapeutic agents and the oncolytic
adenovirus is a potential therapeutic for mesothelioma.
PMID- 23154557
TI - Incidence and survival of malignant pleural mesothelioma in norway: a population
based study of 1686 cases.
AB - BACKGROUND: Asbestos-related malignant pleural mesothelioma is one of the most
lethal tumor types. The advent of antimetabolite treatment as pemetrexed,
introduced in the early 2000s, may have increased survival on a population basis.
In this study, we have analyzed population-based incidence and survival data over
the last 40 years. METHODS: Complete national data on 1686 patients from the
Cancer Registry of Norway sampled from 1970 to 2009 are presented, with incidence
rates in 5-year periods. Relative survival for 1 year and 3 years and median
survival in 5-year intervals were calculated. RESULTS: The incidence of malignant
pleural mesothelioma has been significantly and steadily increasing from 1970
until 2009, with 50 patients diagnosed in the period 1970-1974 and 377 diagnosed
in 2005-2009. The incidence was highest among men in all time periods. A slight
decline was observed in the last period. The 1-year survival rate increased from
20.7% to 44.0% during the period 1970-2009, whereas the 3-year survival rate
remained below 10%. Median survival increased from 4.0 months in the first period
to 9.3 months in the last period. CONCLUSIONS: The incidence of malignant pleural
mesothelioma follows the curve of asbestos exposure with a 20- to 40-year lag.
There has been a significant increase in survival, most likely because of earlier
diagnosis and improvements in cytostatic treatment.
PMID- 23154558
TI - Tomotherapy after pleurectomy/decortication or biopsy for malignant pleural
mesothelioma allows the delivery of high dose of radiation in patients with
intact lung.
AB - INTRODUCTION: This study aimed to assess the safety of high doses of radiation
delivered with tomotherapy to the intact lung after radical
pleurectomy/decortication or biopsy for malignant pleural mesothelioma (MPM).
METHODS: Twenty-eight patients were enrolled in this prospective study and
underwent adjuvant or definitive tomotherapy after radical
pleurectomy/decortication (n = 20) or pleural biopsy (n = 8) for MPM. The dose
prescribed to the planning target volume, defined as the entire hemithorax,
including chest-wall incisions and drain sites and excluding the intact lung, was
50 Gy delivered in 25 fractions. All patients underwent fluorodeoxyglucose
positron emission tomography for staging after surgery. Any fluorodeoxyglucose
avid areas or regions of particular concern for residual disease were given a
simultaneous boost of radiotherapy to 60 Gy. Specific lung dosimetric parameters
were reported. Toxicity was graded using the modified Common Toxicity Criteria
version 3.0. RESULTS: The median follow-up was of 19 months (range, 6-29 months).
Five patients (17.8%) experienced severe respiratory symptoms corresponding to
grade 2 pneumonitis in three cases, and grade 3 pneumonitis in two cases. No
fatal respiratory toxicity was reported. Controlateral lung V5 was strongly
correlated with the risk of pneumonitis. Patients who developed grade 2 and 3
pneumonitis had a higher controlateral lung V5 (mean V5=32%) than those without
pneumonitis (mean V5=17%) (p=0.002). Other two grade 3 toxicities were
registered: one severe pain to the chest wall, and one severe thrombocytopenia.
CONCLUSIONS: Tomotherapy allows the safe delivery of high dose of radiation to
the hemithorax of MPM patients with intact lung.
PMID- 23154559
TI - Thymoma-a clinico-pathological long-term study with emphasis on histology and
adjuvant radiotherapy dose.
AB - INTRODUCTION: To evaluate prognostic factors of thymic epithelial tumors (TETs)
with particular reference to histology and the dose-response relationship of
adjuvant radiotherapy. METHODS: Retrospective study with central pathological
review on patients resected for TET between 1966 and 2004 at a single
institution. Prognostic factors were identified using Cox regression analysis.
RESULTS: From 93 patients with TET, 33.3% relapsed and 47.3% died. Cause of death
was known in 64% and attributed to TET in 25%. Myasthenia gravis was associated
with superior disease-free survival (DFS) and overall survival (OS). Tumors
smaller than 8.5 cm had a significantly better prognosis. With a median follow-up
of 9.8 years actuarial OS at 5, 10, and 20 years were 96%, 92%, and 47% in stage
I; 85%, 61%, and 53% in stage II; 72%, 39%, and 15% in stage III and IV. Advanced
stage and incomplete resection had a negative impact on DFS and OS. According to
histology (WHO type A, AB, B1; favorable; versus WHO type B2, B3; intermediate;
versus thymic carcinoma, unfavorable) three prognostic groups were discernible.
On multivariate analysis, tumor size, and stage emerged as prognostic factors,
but neither histology nor myasthenia. Postoperative radiotherapy was administered
in 27 patients (median dose 50.8 Gy). Doses in excess of 50 Gy were associated
with significantly improved DFS and OS. CONCLUSIONS: Tumor stage, histology,
complete resection, and tumor size had a significant impact on survival.
Myasthenia may facilitate early detection and is correlated with superior
survival. When postoperative radiotherapy is administered, doses above 50 Gy may
improve outcome.
PMID- 23154560
TI - Identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line, LC
2/ad.
AB - Rearranged during transfection (RET) fusions have been newly identified in
approximately 1% of patients with primary lung tumors. However, patient-derived
lung cancer cell lines harboring RET fusions have not yet been established or
identified, and therefore, the effectiveness of an RET inhibitor on lung tumors
with endogenous RET fusion has not yet been studied. In this study, we report
identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line LC
2/ad. LC-2/ad showed distinctive sensitivity to the RET inhibitor, vandetanib,
among 39 non-small lung cancer cell lines. The xenograft tumor of LC-2/ad showed
cribriform acinar structures, a morphologic feature of primary RET fusion
positive lung adenocarcinomas. LC-2/ad cells could provide useful resources to
analyze molecular functions of RET-fusion protein and its response to RET
inhibitors.
PMID- 23154561
TI - Giant sternal condrosarcoma.
PMID- 23154562
TI - The cancer stem-cell hypothesis: its emerging role in lung cancer biology and its
relevance for future therapy.
AB - The cancer stem-cell (CSC) hypothesis suggests that there is a small subset of
cancer cells that are responsible for tumor initiation and growth, possessing
properties such as indefinite self-renewal, slow replication, intrinsic
resistance to chemotherapy and radiotherapy, and an ability to give rise to
differentiated progeny. Through the use of xenotransplantation assays, putative
CSCs have been identified in many cancers, often identified by markers usually
expressed in normal stem cells. This is also the case in lung cancer, and the
accumulated data on side population cells, CD133, CD166, CD44 and ALDH1 are
beginning to clarify the true phenotype of the lung cancer stem cell.
Furthermore, it is now clear that many of the pathways of normal stem cells,
which guide cellular proliferation, differentiation, and apoptosis are also
prominent in CSCs; the Hedgehog (Hh), Notch, and Wnt signaling pathways being
notable examples. The CSC hypothesis suggests that there is a small reservoir of
cells within the tumor, which are resistant to many standard therapies, and can
give rise to new tumors in the form of metastases or relapses after apparent
tumor regression. Therapeutic interventions that target CSC pathways are still in
their infancy and clinical data of their efficacy remain limited. However
Smoothened inhibitors, gamma-secretase inhibitors, anti-DLL4 antagonists, Wnt
antagonists, and CBP/beta-catenin inhibitors have all shown promising anticancer
effects in early studies. The evidence to support the emerging picture of a lung
cancer CSC phenotype and the development of novel therapeutic strategies to
target CSCs are described in this review.
PMID- 23154563
TI - Intravascular lymphoma as a cause of respiratory failure.
PMID- 23154564
TI - A dramatic response to crizotinib in a non-small-cell lung cancer patient with
IHC-positive and FISH-negative ALK.
PMID- 23154565
TI - First case of combined small-cell lung cancer with adenocarcinoma harboring EML4
ALK fusion and an exon 19 EGFR mutation in each histological component.
PMID- 23154566
TI - Adopting integrated care pathways in non-small-cell lung cancer.
PMID- 23154567
TI - Antibody independent microfluidic cell capture of circulating tumor cells for the
diagnosis of cancer.
PMID- 23154568
TI - Oncogenic fusions involving exon 19 of ALK.
PMID- 23154570
TI - A phase I study of concurrent external beam radiotherapy with weekly topotecan
for primary treatment of locally advanced lung cancers.
PMID- 23154571
TI - Unexpected doxorubicin-mediated cardiotoxicity in sisters: possible role of
polymorphisms in histamine n-methyl transferase.
AB - The anthracycline anticancer agent doxorubicin has long been recognized to induce
a dose-limiting cardiotoxicity and may be associated with genes relevant to
doxorubicin disposition. Recent reports suggest a role for a number of single
nucleotide polymorphisms in anthracycline cardiotoxicity in children. We describe
two adult sisters with anthracycline cardiotoxicity that developed after a
relatively low dose of doxorubicin. One sister carried the variant genotype for
histamine N-ethyl transferase (HNMT, rs17583889) while the other was
heterozygous, suggesting a similar role for these genotypes in adults with
anthracycline cardiotoxicity. Although this requires further study, these
genotypes may be important in the clinical dosing, or use of the liposomal
formulation of doxorubicin.
PMID- 23154572
TI - Severe infusion reactions to brentuximab vedotin in two patients with Hodgkin
lymphoma previously treated with allogeneic stem cell transplantation.
AB - Brentuximab vendotin is a monoclonal antibody approved in August 2011 for use in
patients with Hodgkin disease and a rare systemic lymphoma known as anaplastic
large cell lymphoma. Brentuximab is approved in patients with Hodgkin disease who
have failed autologous transplantation or after failure of at least two prior
multi-agent chemotherapy regimens but has not been studied following allogeneic
transplantation. Four patients with relapsed Hodgkin disease have been treated at
our institution with at least two doses of brentuximab vendotin. Two patients
have experienced significant infusion reactions on multiple occasions, and two
patients have tolerated the infusions well. During phase 2 trials, there were no
reports of Grade 3 or 4 infusion-related reactions. Both patients with reactions
had relapsed following allogeneic stem cell transplants, while neither of the
patients who tolerated the infusions had undergone transplantation. We report our
experience with brentuximab vendotin-treated patients at our institution,
focusing on the two post-allogeneic patients who experienced multiple significant
infusion reactions. This report evaluates possible mechanisms behind their
reactions, including previous allogeneic stem cell transplantation as a likely
precipitating factor.
PMID- 23154573
TI - Successful treatment of nilotinib-induced pleural effusion with prednisone.
AB - Chronic myeloid leukemia is characterized by a unique reciprocal translocation
between chromosomes 9 and 22 resulting in deregulated tyrosine kinase activity.
Tyrosine kinase inhibitors, such as imatinib, dasatinib, and nilotinib have
revolutionized treatment of Chronic myeloid leukemia. However, tyrosine kinase
inhibitors' use has presented new challenges in managing both acute and chronic
toxicities, particularly 'off-target' toxicities like pleural effusion. Pleural
effusions are seen less often with imatinib and very rarely with nilotinib. A 66
year-old male presented to emergency department with complaints of mild chest
pain and dyspnea of 3 days duration with progressive worsening, including dyspnea
at rest. Patient was currently taking nilotinib after failing imatinib for
chronic myeloid leukemia. Nilotinib was put on hold. After exclusion of cardiac
and pulmonary etiologies patient was treated for community acquired pneumonia
with minimal improvement. Despite the very low incidence of pleural effusion with
nilotinib (<1%), he was started on 20 mg of prednisone PO for 3 days. Patient had
a dramatic improvement within 48 h after beginning prednisone. This treatment
approach suggests that pleural effusions associated with nilotinib can be
successfully treated in the same way as pleural effusions associated with
dasatinib.
PMID- 23154574
TI - Cetuximab infusion reactions: French pharmacovigilance database analysis.
AB - OBJECTIVES: To compare characteristics of patients exhibiting cetuximab infusion
reactions or another adverse drug reaction related to cetuximab and to identify
factors associated with the severity of cetuximab infusion reactions. METHODS:
All cases of adverse drug reaction reported with cetuximab from 1985 to 2010 were
extracted from the French Pharmacovigilance database. The severity of infusion
reactions was assessed according to the NCI-CTCAE criteria (v4.0). Multiple
logistic regression analysis was performed to identify factors associated with
the severity of infusion reactions. RESULTS: Among the 602 adverse drug reaction
reported with cetuximab during the study period, 374 infusion reactions were
identified. Indication is more likely to be head and neck than colorectal cancer
among patients experiencing an infusion reaction (p < 0.001). Among the seven
deaths related to an infusion reaction, five patients were treated for head and
neck cancer. Infusion reactions were more likely to be severe when they occurred
during the first administration (OR = 7.40 95% CI [2.21-24.71]), adjusted for
age, sex, region of France, quarter of the year, indication, year of occurrence,
and premedication. CONCLUSION: Our study found that reports of infusion reactions
more often concerned patients treated for head and neck cancer, that in these
patients the adverse drug reaction was more often fatal and severe infusion
reactions were more likely during the first administration. In daily practice,
the close monitoring of patients during the first infusion, especially patients
with head and neck cancer, is recommended. Considering the possible
immunoglobulin E-mediated mechanism, reliable tests for their detection need to
be readily available.
PMID- 23154575
TI - Plaque-stabilizing effect of angiotensin-converting enzyme inhibitor and/or
angiotensin receptor blocker in a rabbit plaque model.
AB - AIM: Previous studies have revealed that blockade of the renin angiotensin system
attenuates plaque vulnerability and reduces cardiovascular events; however, few
studies have compared the effects of an angiotensin-converting enzyme inhibitor
(ACEI) with an angiotensin receptor blocker (ARB) and evaluated combination
therapy. The objective of this study was to compare the efficacy and mechanisms
of plaque stabilization by ACEI or ARB and to determine the effects of
combination therapy. METHODS: Twenty-eight male Japanese white rabbits were fed a
high-cholesterol diet after balloon injury of the carotid arteries, then
separated into ACEI (n= 7; imidapril 0.5 mg/kg/day), ARB (n= 7; TA606 4.5
mg/kg/day), combination (n= 7; imidapril 0.5 mg/kg/day+TA606 4.5 mg/kg/day), and
vehicle (n= 7) groups. RESULTS: No difference in plaque volume was identified
among the 4 groups. ACEI or ARB increased the thickness of the fibrous cap,
collagen content and the number of smooth muscle cells in the intima (% smooth
muscle cell in intima: ACEI, 36.3%; ARB, 36.4%; vehicle, 14.9%), and reduced the
accumulation of macrophages (% macrophages in intima: ACEI, 20.1%; ARB, 24.0%;
vehicle, 37.9%), suggesting the plaque-stabilizing effects of each drug. ACEI
reduced matrix metalloproteinase (MMP)-9 expression and gelatinolytic activity in
the intima. While ARB did not change gelatinolytic activity, accumulation ot T
cell in the intima was suppressed. Combination therapy did not show additive
effects. CONCLUSION: These results suggest that ACEIs and ARBs have similar, but
not additive, plaque-stabilizing effects. Each agent showed specific effects,
with ACEIs decreasing gelatinolytic activity and ARBs suppressing T cell
accumulation.
PMID- 23154576
TI - High prevalence of normal waist circumference in Japanese employees with a
cluster of metabolic abnormalities.
PMID- 23154577
TI - Acute effects of postprandial aerobic exercise on glucose and lipoprotein
metabolism in healthy young women.
AB - AIM: To investigate the acute effects of postprandial exercise on glucose and
lipoprotein metabolism after the intake of glucose with or without fat cream in
healthy but sedentary young women. METHODS: Healthy young Japanese women with a
sedentary lifestyle, normal weight (18.5<=BMI<25), normal ovarian cycle, and
apolipoprotein (apo) E3/3 were enrolled as participants. They ingested 1 g/kg
body weight of glucose only or glucose supplemented with 1 g/kg oral fat
tolerance test (OFTT) cream 4 (0.35 g/kg as fat) with or without postprandial
walking exercise on a motorized treadmill (ca. 50%V(.)o(2)max for 30 min) 20 min
after intake of the beverage. Each subject performed 4 trials in a randomized,
cross-over design. Venous blood was drawn before (0 h), and 20 min, 1, 2, 4, and
6 h after ingestion. RESULTS: Postprandial exercise alleviated the sharp rise of
serum glucose and insulin, and transiently mitigated the decrease of free fatty
acids (FFA) after ingestion of the glucose-only beverage. Although no fat was
contained in the glucose beverage, transient apoB48 secretion was observed
without the rise of serum triglyceride (TG) and remnant-like particle (RLP)-TG,
suggesting that apoB48-containing lipoprotein particles with little TG were
released by the exercise. Serum apoB48 concentrations at 6 h had decreased to
levels lower than the baseline (0 h, after 12-h overnight fast) with or without
exercise, suggesting that the 12-h overnight fast may not have been a 'true'
fast. Similarly, postprandial exercise suppressed the sharp rise of serum glucose
and insulin, and transiently mitigated the decrease of FFA after the ingestion of
glucose with OFTT cream. Postprandial exercise stimulated the transient secretion
of apoB48-containing TG-rich lipoproteins (TRL) with a rapid rise of serum
apoB48, TG, and RLP-TG; however, the subsequent course of lipemia was not
significantly changed. Serum apoB48 and RLP-TG values did not return to the
baseline even after 6 h, suggesting that postprandial lipoprotein metabolism was
not finished at the end of the experiment. CONCLUSION: Postprandial aerobic
exercise alleviated the glycemic peak at 1 h associated with insulin 'sparing'.
The effect of exercise on fat metabolism was transient, enhancing the secretion
of intestinal TRL at an early phase, but no further significant effects were
observed. Postprandial exercise transiently stimulated the secretion of apoB48
after glucose intake without a fat load.
PMID- 23154578
TI - Effects of lutein supplement on serum inflammatory cytokines, ApoE and lipid
profiles in early atherosclerosis population.
AB - AIM: The purpose of this study was to determine the effects of lutein supplement
on serum cytokines, apoE and lipoprotein profiles in early atherosclerosis
population. METHODS: Early atherosclerosis patients (n= 65) were randomized to
receive placebo (A+P, n= 31) or 20 mg/d lutein (A+L, n= 34) for 3 months.
RESULTS: Serum lutein increased significantly compared to baseline after lutein
supplements in A+L group (p<0.001). Lutein supplements resulted in a significant
decrease in serum interleukin-6 (IL-6) and monocyte chemoattractant protein-1
(MCP-1) at 3 month in A+L group (p<0.05). Intragroup comparison revealed a
significant difference in the changes of serum MCP-1 between A+L and A+P groups
(p= 0.021). The serum low-density lipoprotein (LDL) and triglyceride (TG)
significantly decreased in A+L group (p<0.05). The changes in serum lutein were
negatively associated with those in serum LDL in A+L group (r=-0.384, p=0.043),
while no such relationship was observed in A+P group (r= 0.087, p= 0.685).
CONCLUSION: An increase in serum lutein after supplementation can reduce
inflammatory cytokines and regulate serum lipids, which may pay important roles
in early atherosclerosis.
PMID- 23154579
TI - An optimum projection and noise reduction approach for detecting rare and common
variants associated with complex diseases.
AB - BACKGROUND: Despite the thrilling advances in identifying gene variants that
influence common diseases, most of the heritable risk for many common diseases
still remains unidentified. One of the possible reasons for this missing
heritability is that the genome-wide association study (GWAS) approaches have
been focusing on common rather than rare single nucleotide variants (SNVs).
Consequently, there is currently a great deal of interest in developing methods
that can interrogate rare variants for association with diseases. METHODS: We
propose a two-step method (termed rPLS) to reveal possible genetic effects
related to rare as well as common variants. The procedure starts with removing
irrelevant variants using penalized regression (regularization) which is followed
by partial least squares (PLS) on the surviving SNVs to find an optimal linear
combination of rare and common SNVs within a genomic region that is tested for
its association with the trait of interest. RESULTS: Simulation settings based on
the 1000 Genomes sequencing data and reflecting real situations demonstrated that
rPLS performs well compared to existing methods especially when there are a large
number of noncausal variants (both rare and common) present in the gene and when
causal SNVs have different effect sizes and directions.
PMID- 23154581
TI - Modeling problem-oriented clinical notes.
AB - OBJECTIVES: To develop a model as a starting-point for developing a problem
oriented clinical notes application as a generic component of an Electronic
Health Record (EHR). METHODS: We used the generic conceptualization of Weed's
problem-oriented medical record (POMR) to link progress notes to problems, and
the Subjective, Objective, Assessment, Plan (SOAP) headings to classify elements
of these notes. Health Level 7 (HL7) Version 3 and Unified Modeling Language
(UML) were used for modeling. We looked especially at the role of Conditions and
Concerns, and how to model these to document clinical reasoning. RESULTS: We
developed a generic HL7-based model for progress notes. In this model the
specific clinical note has a condition as its reason. An assertion can be made
about a condition. Any condition, observation or procedure can be a concern that
has to be tracked. Utmost important is the relationship between constituting
parts of a progress note and specially between progress notes by linking a
progress note to conditions that are part of an earlier progress note. From this
model a comprehensive hierarchical condition tree can be built. Several views,
such as chronological, SOAP and condition-oriented, are possible. The clinical
notes application is used in daily clinical practice. The model meets explicit
design criteria and clinical needs. CONCLUSIONS: With the comprehensive HL7
standard it is possible to model and map progress notes using SOAP headings and
POMR methodology. We have developed a generic, flexible and applicable paradigm
by using acts for each assessment that refer to a condition (1), by separating
conditions from concerns (2), and by an extensive use of the working list act
(3).
PMID- 23154580
TI - The metabolic activity of gut microbiota in obese children is increased compared
with normal-weight children and exhibits more exhaustive substrate utilization.
AB - OBJECTIVE: The gut microbiota contribute otherwise impossible metabolic functions
to the human host. Shifts in the relative proportions of gut microbial
communities in adults have been correlated with intestinal disease and have been
associated with obesity. The aim of this study was to elucidate differences in
gut microbial compositions and metabolite concentrations of obese versus normal
weight children. MATERIALS AND METHODS: Fecal samples were obtained from obese
(n=15; mean body mass index (BMI) s.d. score=1.95) and normal-weight (n=15; BMI
s.d. score=-0.14) Swiss children aged 8-14 years. Composition and diversity of
gut microbiota were analyzed by qPCR and temperature gradient gel electrophoresis
(TGGE). RESULTS: No significant quantitative differences in gut microbiota
communities of obese and normal-weight children were identified. Microbial
community profiling by TGGE revealed a high degree of both intra- and intergroup
variation. Intergroup comparison of TGGE profiles failed to identify any distinct
populations exclusive to either obese or normal-weight children. High-pressure
liquid chromatography analysis identified significantly higher (P<0.05)
concentrations of short-chain fatty acids (SCFA) butyrate and propionate in obese
versus normal-weight children. Significantly lower concentrations of intermediate
metabolites were detected in obese children, suggesting exhaustive substrate
utilization by obese gut microbiota. CONCLUSIONS: Our results indicate that a
dysbiosis may be involved in the etiology of childhood obesity. In turn, aberrant
and overactive metabolic activity within the intestine could dictate survival or
loss of individual microbial communities, leading to the altered population
ratios previously identified in adult obesity.
PMID- 23154582
TI - Applications of asymmetric organocatalysis in medicinal chemistry.
AB - In the last decade, organocatalysis, the use of small chiral organic molecules as
catalysts, has proven to be a valuable and attractive tool for the synthesis of
enantiomerically enriched molecules. A number of organocatalysts and processes,
such as one-pot, tandem, cascade or multicomponent reactions, have been reported
to date. Furthermore, the many advantages of organocatalysis - robust, non-toxic,
affordable, inert atmosphere, easy reaction manipulation, etc. - allow the
preparation of bioactive compounds using simple and metal-free procedures, thus
avoiding false positives in the biological evaluation. This mini-review focuses
on medicinal chemistry programs that have synthesized biologically active
compounds using one or more organocatalytic steps. In this respect, the potential
of organocatalytic methods for enabling the chemical synthesis of important
medicinal targets will be highlighted.
PMID- 23154583
TI - A new approach to kinematic feature extraction from the human right ventricle for
classification of hypertension: a feasibility study.
AB - This work presents a novel approach to analyze the function of the human right
ventricle (RV) by deriving kinematic features of the relative change in shape
throughout the cardiac cycle. The approach is anatomically consistent, allows
direct comparison across populations of individuals, and potentially provides new
metrics to improve the diagnosis and understanding of cardiovascular diseases
such as pulmonary hypertension (PH). The details of the approach are presented,
which includes a variation of harmonic topological mapping and proper orthogonal
decomposition techniques, with particular focus on their applicability with
respect to untagged cardiac imaging data. Results are shown for the decomposition
of a collection of clinically obtained human RV endocardial surfaces segmented
from cardiac computed tomography imaging into the fundamental shape change
features for individuals both with and without PH. The features are shown to be
consistent and converging towards intrinsically physiological components for the
heart, and may potentially represent a new set of features for classifying the
progressive change in RV function caused by PH, particularly in comparison to
traditional clinical metrics.
PMID- 23154584
TI - Distinct transcriptional control in major immunogenetic subsets of chronic
lymphocytic leukemia exhibiting subset-biased global DNA methylation profiles.
AB - Chronic lymphocytic leukemia (CLL) can be divided into prognostic subgroups based
on the IGHV gene mutational status, and is further characterized by multiple
subsets of cases with quasi-identical or stereotyped B cell receptors that also
share clinical and biological features. We recently reported differential DNA
methylation profiles in IGHV-mutated and IGHV-unmutated CLL subgroups. For the
first time, we here explore the global methylation profiles of stereotyped
subsets with different prognosis, by applying high-resolution methylation arrays
on CLL samples from three major stereotyped subsets: the poor-prognostic subsets
#1 (n = 15) and #2 (n = 9) and the favorable-prognostic subset #4 (n = 15).
Overall, the three subsets exhibited significantly different methylation
profiles, which only partially overlapped with those observed in our previous
study according to IGHV gene mutational status. Specifically, gene ontology
analysis of the differentially methylated genes revealed a clear enrichment of
genes involved in immune response, such as B cell activation (e.g., CD80, CD86
and IL10), with higher methylation levels in subset #1 than subsets #2 and #4.
Accordingly, higher expression of the co-stimulatory molecules CD80 and CD86 was
demonstrated in subset #4 vs. subset #1, pointing to a key role for these
molecules in the crosstalk of CLL subset #4 cells with the microenvironment. In
summary, investigation of three prototypic, stereotyped CLL subsets revealed
distinct DNA methylation profiles for each subset, which suggests subset-biased
patterns of transcriptional control and highlights a key role for epigenetics
during leukemogenesis.
PMID- 23154585
TI - Hypertension and the J-curve phenomenon: implications for tight blood pressure
control.
PMID- 23154586
TI - Response to Rai.
PMID- 23154588
TI - Increased blood viscosity is associated with reduced renal function and elevated
urinary albumin excretion in essential hypertensives without chronic kidney
disease.
AB - Increased blood viscosity reduces blood flow and elevates vascular resistance in
the cardiovascular system. The aim of this study was to elucidate how blood
viscosity could affect renal function and eventually contribute to renal damage
in essential hypertensives (EHT). In 164 untreated EHT without apparent renal
damage (96 men, 56+/-12 years old, creatinine clearance 123+/-33 ml min(-1) per
1.73 m(2) and urinary albumin excretion 19+/-19 mg per day), blood and plasma
viscosity was determined using a falling ball microviscometer. Blood viscosity
correlated negatively with creatinine clearance (r=-0.185, P=0.018) and
positively with urinary albumin excretion (r=0.253, P=0.001). This indicated that
increased blood viscosity is associated with reduced renal function and worsening
of albuminuria in EHT. Stepwise multiple regression analysis identified blood
viscosity as an independent determinant of creatinine clearance (R(2)=0.058) and
urinary albumin excretion (R(2)=0.216). In conclusion, increased blood viscosity
may be a risk for development of renal disease in EHT.
PMID- 23154587
TI - The angiotensin II type 1 receptor blocker olmesartan preferentially improves
nocturnal hypertension and proteinuria in chronic kidney disease.
AB - Accumulated evidence suggests that an altered ambulatory blood pressure (BP)
profile, particularly elevated nighttime BP, reflects target organ injury and is
a better predictor of further cardiorenal risk than the clinic BP or daytime BP
in hypertensive patients complicated by chronic kidney disease (CKD). In this
study, we examined the beneficial effects of olmesartan, an angiotensin II type 1
receptor blocker (ARB), on ambulatory BP profiles and renal function in
hypertensive CKD patients. Forty-six patients were randomly assigned to the
olmesartan add-on group (n=23) or the non-ARB group (n=23). At baseline and after
the 16-week treatment period, ambulatory BP monitoring was performed and renal
function parameter measurements were collected. Although the baseline clinic BP
levels and the after-treatment/baseline (A/B) ratios of clinic BP levels were
similar in the olmesartan add-on and non-ARB groups, the A/B ratios of ambulatory
24-h and nighttime BP levels in the olmesartan add-on group were significantly
lower. Furthermore, the A/B ratios of urinary protein, albumin and type IV
collagen excretion in the olmesartan add-on group were significantly lower than
those in the non-ARB group (urinary protein excretion, 0.72+/-0.41 vs. 1.45+/
1.48, P=0.030; urinary albumin excretion, 0.73+/-0.37 vs. 1.50+/-1.37, P=0.005;
urinary type IV collagen excretion, 0.87+/-0.42 vs. 1.48+/-0.87, P=0.014) despite
comparable A/B ratios for the estimated glomerular filtration rate in the two
groups. These results indicate that in hypertensive patients with CKD, olmesartan
add-on therapy improves the ambulatory BP profile via a preferential reduction in
nighttime BP with concomitant renal injury inhibition.
PMID- 23154589
TI - Aliskiren vs. other antihypertensive drugs in the treatment of hypertension: a
meta-analysis.
AB - To investigate the antihypertensive effects and tolerability of aliskiren in
comparison with other antihypertensive drugs and placebo in patients with
hypertension, a meta-analysis was performed of studies published between 1950 and
2012. A systematic literature search of MEDLINE and the Cochrane Library was
conducted for randomized controlled trials. Weighted mean differences and
relative risk with 95% confidence intervals were calculated for continuous and
dichotomous data, respectively. In all, 14 studies with 6741 participants were
included in the present meta-analysis. Nine studies included trial arms with
placebo, four included angiotensin (Ang) AT1 receptor blockers (ARBs), three
included Ang-converting enzyme inhibitors (ACEIs), two included calcium channel
blockers (CCBs), one included a beta-blocker, and one included
hydrochlorothiazide (HCTZ). We found that aliskiren, which lowered blood pressure
(BP) effectively in patients with mild-to-moderate hypertension, was similar to
HCTZ but inferior to CCBs in BP reduction, response rates and control rates.
Furthermore, aliskiren was superior to ACEIs in lowering diastolic BP (DBP),
while it had similar effects to ACEIs on systolic BP (SBP) reduction, response
rates and control rates. Additionally, the present meta-analysis showed the
superiority of atenolol over aliskiren in DBP reduction and BP response but
showed that atenolol was inferior in SBP reduction and BP control. No difference
was found in the rates of therapeutic response between aliskiren and ARBs, while
more patients achieved BP control with aliskiren. Further studies will be needed
to determine the antihypertensive effects and tolerability of aliskiren in
comparison with other antihypertensive drugs.
PMID- 23154590
TI - The effects of telmisartan alone or with hydrochlorothiazide on morning and 24-h
ambulatory BP control: results from a practice-based study (SURGE 2).
AB - Observational studies have shown that 24-h and morning ambulatory blood pressure
(BP) control is low. This large-scale, practice-based study evaluated the effects
of telmisartan 40 or 80 mg alone or in combination with hydrochlorothiazide
(HCTZ) 12.5 mg on these BP parameters over 8 weeks; treatment was adjusted if
clinic BP remained >=140/90 mm Hg. A total of 863 patients were evaluated
(baseline mean clinic BP, morning and 24-h ambulatory BP: 155+/-15/93+/-10 mm Hg,
137+/-15/83+/-11 mm Hg, 133+/-14/79+/-10 mm Hg, respectively; 68% were previously
treated at baseline). Telmisartan with/without HCTZ significantly reduced the
mean morning ambulatory BP (-8.2/-4.9 mm Hg), daytime ambulatory BP (-8.0/-4.7 mm
Hg), 24-h ambulatory BP (-7.9/-4.7 mm Hg) and clinic BP (-22.3/-13.2 mm Hg) (all
P<0.001) in previously untreated and in treated patients who switched to
telmisartan and telmisartan/HCTZ. After treatment with telmisartan with/without
HCTZ, the morning ambulatory BP control increased from 36.5 to 64.4%; daytime
ambulatory BP control increased from 40.8 to 67.6%; 53.0% of patients achieved 24
h ambulatory BP <125/80 mm Hg and 62% achieved <130/80 mm Hg targets. Only 0.8%
(7/863) reported an adverse event. In summary, telmisartan and telmisartan/HCTZ
increased smooth 24-h BP control in daily management of hypertension.
PMID- 23154592
TI - Effects and cost-effectiveness of a guideline-oriented primary healthcare
hypertension management program in Beijing, China: results from a 1-year
controlled trial.
AB - Hypertension control rates are unacceptably low in China. The present study
demonstrates if a customized, guideline-oriented training program can cost
effectively improve hypertension management in primary healthcare. Four typical
community health centers in Beijing were selected and randomized to intervention
or control (one urban and one rural each). A sample of 140 patients with
hypertension and blood pressure uncontrolled was recruited from each center.
Primary healthcare providers in intervention centers provided management to the
recruited patients for 1 year after receiving training with customized
hypertension management guidelines, and primary healthcare providers in control
provided with usual care. Intention-to-treat analysis showed that hypertension
control (systolic blood pressure (SBP) <140 mm Hg and diastolic blood pressure
(DBP) <90 mm Hg)) rate was significantly higher in interventions than controls at
month 3 (42.1% vs. 34.3% in urban and 30.7% vs. 10.0% in rural centers) and the
trend increased to month 12 (70.7% vs. 40.0% in urban and 72.9% vs. 27.9% in
rural); P-values by logistic mixed model were all <0.001 for both urban and rural
after adjustment for baseline multiple variables including blood pressure. Mean
reductions of SBP and DBP were significantly larger in interventions. The
intervention was cost-saving, with an average incremental cost-saving of US$ 20.3
per patient in urban sites and $ 7.0 per patient in rural sites. Corresponding
results from per-protocol analysis were very similar. The customized, guideline
oriented hypertension management program in primary healthcare in China
effectively improved blood pressure control and was cost-saving.
PMID- 23154593
TI - An update on the drug treatment of neuropathic pain. Part 2: antiepileptics and
other drugs.
AB - In An update on the drug treatment of neuropathic pain. Part 1: antidepressants,
we highlighted the problems associated with the management of neuropathic pain
and reviewed the use of antidepressants. This month we discuss the use of
antiepileptic drugs and other analgesics.
PMID- 23154591
TI - Effects of valsartan on progression of kidney disease in Japanese hypertensive
patients with advanced, predialysis, chronic kidney disease: Kanagawa Valsartan
Trial (KVT).
AB - Suppression of the renin-angiotensin system is known to slow progression of
chronic kidney disease (CKD). However, few trials have been performed with
Japanese patients. This study investigated whether the angiotensin receptor
blocker (ARB) valsartan would delay the progression of kidney disease more
effectively than conventional treatment in Japanese hypertensive patients with
advanced, predialysis CKD. In a multicenter, randomized, open-label trial, 303
patients with hypertension and CKD with serum creatinine levels ?2.0 mg dl(-1)
were assigned to receive either conventional therapy plus valsartan (valsartan
add-on group) or conventional therapy without ARB (control group). The primary
outcome was a change in serum creatinine levels. Changes in urinary protein
levels and time to onset of renal events were analyzed as secondary end points.
There were no between-group differences in blood pressure during the study.
Changes in serum creatinine and urinary protein levels did not differ between the
groups. However, the rate of renal events, including doubling of serum creatinine
levels or end-stage renal disease, was significantly lower in the valsartan add
on group than in the control group. The addition of valsartan decreased the risk
by 42.6% after adjustment for baseline variables. The addition of valsartan to
conventional therapy significantly slowed the rate of renal function decline and
delayed the need for renal replacement therapy in Japanese hypertensive patients
with advanced CKD.
PMID- 23154594
TI - Fidaxomicin for the treatment of Clostridium difficile infections.
AB - Clostridium difficile infection (CDI), also known as C. difficile-associated
disease or diarrhoea (CDAD), is an important cause of hospital-acquired diarrhoea
with disease severity ranging from mild diarrhoea to fulminant colitis. In
addition, over 40% of new cases of CDI occur outside hospital. ? Fidaxomicin
(Dificlir - Astellas), the first antibiotic in a new class called macrocyclics,
has recently been licensed for the treatment of C. difficile infection in adults.
Here we provide a brief overview of C. difficile infection and assess how
fidaxomicin fits with current management strategies for treatment of such
infections.
PMID- 23154596
TI - Judging too quickly?
PMID- 23154598
TI - Current world literature.
PMID- 23154597
TI - What do you do? Perceptions of nurse manager responsibilities.
PMID- 23154600
TI - Improvement in hematopoiesis after iron chelation therapy with deferasirox in
patients with aplastic anemia.
AB - Iron overload due to regular transfusions of packed red cells can cause multiple
organ damage. Iron chelation therapy (ICT) is important in patients with aplastic
anemia (AA) who require blood transfusions as supportive management. With the
introduction of the oral iron chelator deferasirox, ICT has become more widely
available and feasible. We studied 4 adult AA patients who had transfusion
induced iron overload and showed hematological improvement after ICT with oral
deferasirox. Following deferasirox treatment, hemoglobin increased and serum
ferritin levels decreased, and the patients subsequently became transfusion
independent. Our experience raises the possibility of the potential benefit of
ICT on hematopoiesis. Further long-term studies in larger patient cohorts are
needed to clarify the effect of the restoration of hematopoiesis after iron
chelation therapy.
PMID- 23154601
TI - Light-responsive polymer nanoreactors: a source of reactive oxygen species on
demand.
AB - Various domains present the challenges of responding to stimuli in a specific
manner, with the desired sensitivity or functionality, and only when required.
Stimuli-responsive systems that are appropriately designed can effectively meet
these challenges. Here, we introduce nanoreactors that encapsulate
photosensitizer-protein conjugates in polymer vesicles as a source of "on demand"
reactive oxygen species. Vesicles made of poly(2-methyloxazoline)
poly(dimethylsiloxane)-poly(2-methyloxazoline) successfully encapsulated the
photosensitizer Rose Bengal-bovine serum albumin conjugate (RB-BSA) during a self
assembly process, as demonstrated by UV-Vis spectroscopy. A combination of light
scattering and transmission electron microscopy indicated that the nanoreactors
are stable over time. They serve a dual role: protecting the photosensitizer in
the inner cavity and producing in situ reactive oxygen species (ROS) upon
irradiation with appropriate electromagnetic radiation. Illumination with
appropriate wavelength light allows us to switch on/off and to control the
production of ROS. Because of the oxygen-permeable nature of the polymer membrane
of vesicles, ROS escape into the environment around vesicles, as established by
electron paramagnetic resonance. The light-sensitive nanoreactor is taken up by
HeLa cells in a Trojan horse fashion: it is nontoxic and, when irradiated with
the appropriate laser light, produces ROS that induce cell death in a precise
area corresponding to the irradiation zone. These nanoreactors can be used in
theranostic approaches because they can be detected via the fluorescent
photosensitizer signal and simultaneously produce ROS efficiently "on demand".
PMID- 23154603
TI - Predictive tools for prostate cancer staging, treatment response and outcomes.
AB - OBJECTIVES: Numerous predictive models relating to prostate cancer staging and
outcomes have been described. We sought to review and categorize these predictive
tools to create a comprehensive reference for physicians who treat prostate
cancer. METHODS: We performed a search of MEDLINE literature from January 1966 to
April 2012 to identify predictive models relating to prostate cancer staging,
treatment, and outcomes in the pre-treated patient. For each model identified,
we describe the outcome predicted, the variables comprising the model, the size
of the cohort on which the tool was developed, predictive discrimination
estimates, and whether internal and/or external validation has been performed.
RESULTS: We identified 80 predictive tools applicable to pre-treated prostate
cancer patients, 30 of which had been externally validated. Tools designed to
predict pathologic stage were the most common; several models focused on
accurately predicting clinically insignificant prostate cancer while another
large proportion focused on the prediction of locally advanced disease (i.e.
extracapsular extension, seminal vesicle involvement, lymph node invasion). Other
models described studied biochemical outcomes following radical prostatectomy,
external beam radiotherapy, or brachytherapy. Very few models addressed the
prediction of metastasis and survival. Finally, several tools incorporated novel
pre-treatment serum biomarkers or magnetic resonance imaging findings into base
models to enhance the accuracy of standard clinicopathologic variables.
CONCLUSION: To deliver optimal, individualized prostate cancer care, treatment
should be tailored to the specific characteristics of each patient and each
tumor. Predictive models may facilitate such an approach and are numerously
described in the literature. While the performance of predictive models is
encouraging, further improvement through inclusion of biomarkers as well as
evaluation of their clinical utility is imperative. Optimally, predictive models
should be further studied in the prospective setting.
PMID- 23154604
TI - Quality perception in the outpatient area of an Urology department. Can we
improve it?
AB - OBJECTIVES: To test patient's satisfaction after consultation in the outpatient
area of the Urology Department in a public hospital using a structured interview.
METHODS: We used the Comunidad Autonoma de Madrid (CAM) standard interview form
modified to include three questions related to the implementation of a 'one
visit'policy and nurses' empowerment. Patients' opinions were gathered with
respect to waiting times in the waiting room, facilities, and staff kindness and
professionalism. Sample size was estimated in 386 patients. The effect of every
predictive factor on the overall satisfaction was tested using the chi square
test. To define the effect of every variable in presence of the rest of
covariates a logistic regression model was used. RESULTS: Participation reached
65.5%. Overall, 86.4% of the patients were satisfied. Irrespectively of the
professional and personal style, the quality perception was homogeneous (p=ns).
Multivariate analysis couldn't disclose any independent predictive variable. Only
the perception in the item 'overall time available for the consultation'
approached statistical significance (p=0.08), with patients scoring high in this
variable getting the highest overall satisfaction scores. CONCLUSIONS: There was
no personal or professional style particularly related with patient satisfaction.
Nevertheless, there is a slight trend towards a higher satisfaction when patients
feel enough time has been spent in their consultation. The new organizational
resources (one-visit clinic and nurses' empowerment) are both welcome but are not
clearly related to patient satisfaction.
PMID- 23154605
TI - Higher second fourth digit ratio predicts higher incidence of prostate cancer in
prostate biopsy.
AB - OBJECTIVES: To analyze the validity of the ratio between the second and fourth
finger (digit ratio; 2D/4D) of the left hand as a predictor for prostate cancer
(PCa) in a group of men undergoing prostate biopsy. METHODS: We prospectively
recruited 204 consecutive patients referred for transrectal prostate biopsy due
to PSA elevation or abnormal digital rectal examination between January 2008 and
June 2009. The same physician performed all clinical examinations, digit ratio
measurements and transrectal biopsy in all cases. Digit ratio determination was
done with a Vernier caliper in the left hand. Patients underwent determination of
hormone profile (testosterone and sexual hormone binding globulin (SHBG)) between
7:00AM and 11:00AM. Age, digital rectal examination, PSA, free PSA, PSA density,
testosterone and SHBG, pathological report and D2 and D4 measurements were
recorded prospectively. RESULTS: Variables age and SHBG were directly related to
PCa. Prostate volume was inversely related to neoplasia. 2D/4D ratio >0,95 (OR
(CI 95%) 4,4 (1,491-13,107) was related to neoplasia. No differences in PCa were
seen regarding PSA, free PSA, PSA density, digital rectal examination and
testosterone. CONCLUSION: High digit ratio predicts PCa in men undergoing
prostate biopsy. Digit ratio >0,95 has 4-fold risk of PCa compared to men with
digit ratio <=0.95.
PMID- 23154606
TI - Clinical profile and epidemiological changes of clear cell renal carcinoma during
12 years in our health area.
AB - OBJECTIVES: To investigate changes in the epidemiology and clinical profile of
patients diagnosed with renal clear cell carcinoma in a community health area
over 12 years. METHODS: Retrospective analysis of epidemiological characteristics
and clinical profile of patients diagnosed with renal clear cell carcinoma in a
health area composed of a population of 353.619 inhabitants from January 1999 to
December 2010. Descriptive statistical and multivariate analysis, Fisher exact
test and Chi-Square were utilized. p<0.05 was accepted as significant. RESULTS:
349 diagnoses of renal mass were reported; 165 of them were clear renal cell
carcinoma. Median age was 70.41 years, and the Female/Male rate was 28% and 72%,
respectively. 4% women and 30% men smoked >=20 cigarettes/day, more frequently
during the period 1999-2001. 52% women and 30% men had hypertension. Hematuria
was the most frequent symptom (23%), more frequent in the period 2007-2010,
followed by abdominal pain (16%) and renal colic(13%). Weight loss (12%) was more
frequent between 1999-2000. Asthenia appeared as the first symptom in 8% of
cases. The tumor was incidentally diagnosed in 20% of cases, more frequently in
the period between 2007-2010. Diagnosis was established in the Urology Department
in 36% of the cases. Stages T1-2 N0 were more frequent between 2007-2010, and M1
between 1999-2000. G3 was more frequent in the entire series. The relative cancer
specific mortality of patients who were surgically treated was less in the last 2
years of the period. CONCLUSIONS: Clear renal cell carcinoma is the most frequent
renal cancer and its incidence is increasing in our environment. It affects more
frequently males than females, and at an earlier age. The last few years are
showing a decrease in the habitual smoker males and an increase in HTN in
females. A tendency has been detected to the early stage clinical diagnosis but
with a higher histopathological grade. It is most frequent diagnosed by a non
Urology speciality.
PMID- 23154607
TI - Robot assisted partial nephrectomy (Da Vinci) in an angiomyolipoma associated to
Wunderlich Syndrome.
AB - OBJECTIVE: To describe a case of renal angiomyolipoma treated by robotic assisted
surgery. METHOD AND RESULTS: We report the case of a 26 year old females patient,
in the context of third month pregnancy, who was diagnosed of spontaneous self
limited retroperitoneal hemorrhage due to renal angiomyolipoma. The patient was
treated conservatively until normal delivery. At the 3rd month postpartum a robot
assisted (Da Vinci S) nephron sparing surgery (partial nephrectomy) was
performed. CONCLUSION: Despite being a benign tumor, there are cases in which the
renal angiomyolipoma requires surgical treatment. To our knowledge, after a
thorough review of the literature, this would be the first reported case of
angiomyolipoma treated with conservative surgery with robotic assistance (Da
Vinci S-HD).
PMID- 23154608
TI - Bladder injury during trans-obturator tape surgery in a patient with previous
colposuspension: is there a connection?
AB - OBJECTIVE: Bladder injuries are quite rare and complex complications of
transobturator tapes in the treatment of female stress urinary incontinence,
with very few published cases. The authors present a case report and discuss
possible injury mechanisms and the role of cystoscopy in this setting. METHODS:
A 51 year-old female with past surgical history of Burch colposuspension
underwent an uneventful transobturator tape surgery. After 15 days, she
complained of dysuria and frequency. Cystoscopy revealed the tape protruding
within the bladder. RESULTS: Reoperation was performed with the sub-urethral
segment of the tape removed by vaginal approach and the vesical one excised
endoscopically. Presently, the patient is asymptomatic. CONCLUSIONS: In patients
with previous incontinence surgical treatments, cystoscopy at the time of surgery
should be considered to exclude and treat eventual injuries, in order to avoid
future complications.
PMID- 23154609
TI - Percutaneous endopyelotomy with electrocautery: modified techniques in the
treatment of ureteropelvic junction obstruction in a child under 2 years.
AB - OBJECTIVE: In recent years new techniques in minimally invasive treatment of
congenital stenosis of ureteropelvic junction have been developed. We report the
treatment of pyeloureteral stenosis in children by percutaneous endopyelotomy.
METHODS: In the work up study of a child (18 months) with abdominal palpable
mass, a severe left hydronephrosis with a renal pelvis diameter of 65 mm and
severely thinned renal parenchyma was found. The diuretic renogram showed an
obstructive pattern with impaired renal function. Initially, a retrograde
dilatation balloon was placed in the ureteropelvic junction under cistoscopic
control. With the patient in modified Valdivia position, percutaneous access to
the renal pelvis was performed. By Seldinger technique and under fluoroscopy
guide, a 5 mm laparoscopic trocar was placed in the renal pelvis. We performed a
percutaneous electrical endopyelotomy of the pyeloureteral junction over the 6 mm
retrograde balloon dilator passed through. We placed an antegrade double J stent
that was removed at 4 weeks uneventfully. RESULT: Good results were assessed
without perioperative or postoperative complications with great improvement in
renal dilatation two years after the intervention. The renogram showed
improvement in the pattern of the curve with a slight increase in differential
renal function. CONCLUSIONS: Percutaneous endopyelotomy in children has important
issues due to the lack of appropriate material. However it is possible to get
good results as a minimally invasive technique. In fact, it could be the ideal
technique in severe hydronephrosis with large renal pelvis that prevents the
surgical or endourological approach.
PMID- 23154610
TI - Tubulocystic renal carcinoma (low grade collecting duct carcinoma).
AB - OBJECTIVE: To report a case of tubulocystic renal carcinoma diagnosed in an
adult, after a work up study for hematuria. METHODS/RESULTS: 59-year-old male, CT
scan was performed during a study for self-limited hematuria showing a 4.2 cm
solid mass with areas suspicious of pseudocystic malignancy. Due to its debut
with hematuria and renal sinus involvement laparoscopic radical nephrectomy was
performed, establishing the diagnosis of tubulocystic carcinoma (low grade
collecting duct carcinoma). CONCLUSION: Tubulocystic carcinoma presents
histological characteristics and a natural history that makes it different from
the classic type of Bellini duct carcinoma, the latter being a rapidly growing
tumor with poor prognosis which is usually diagnosed in advanced stages.
PMID- 23154611
TI - Vesicoureteral refulx in overactive bladder: medical resolution through botulin
toxin injection.
AB - OBJECTIVE: Overactive bladder may have a neurogenic or non neurogenic origin.
Sometimes, as a result of detrusor overactivity, disorders of the upper urinary
tract function may appear. One of these alterations may be the appearance of
associated vesicoureteral reflux. The treatment of overactive bladder may be
done with anticholinergic drugs and if there is not response the use of botulin
toxin type A is approved. The aim of this case report is to demonstrate the
effect of botulin toxin type A in the treatment of overactive bladder and
vesicoureteral reflux secondary to the overactive bladder. METHOD: We present
the case of a 10-year-old patient without significant past medical history. When
he was one year old he had a urinary infection and voiding cystourethrogram
showed grade 1 right vesicoureteral reflux. When he was 4 year old he presented
several episodes of pyelonephritis and then he was diagnosed of severe bilateral
vesicoureteral reflux, which did not respond to treatment with Macroplastic (r)
or Deflux (r). Urodynamic study was performed showing overactive bladder with
decreased bladder compliance. RESULTS: We performed intravesical injection of 200
U of botulin toxin type A and vesicoureteral reflux disappeared and urodynamic
study improved. One year later we re-injected botulin toxin type A (300 U) and
we repeated the injection after one year (300 U). The patient is currently well,
without changes in the urodynamic study and without vesicoureteral reflux.
CONCLUSION: Repeated injections of botulin toxin type A has shown great efficacy
in the treatment of overactive bladder in children with vesicoureteral reflux
improved secondary.
PMID- 23154612
TI - Complete bilateral pelvicalyceal system duplication.
PMID- 23154613
TI - Renal pelvis tumour.
PMID- 23154614
TI - Using alkaline-earth metal ions to tune structural variations of 1,3,5
benzenetricarboxylate coordination polymers.
AB - Alkaline-earth metal ions were used to tune four new heterometallic frameworks,
{[Cd(2.07)Mg(0.93)(BTC)(2)(H(2)O)(4)].2H(2)O}(n) (1),
{[Cd(2)Ca(BTC)(2)(H(2)O)(4)].2H(2)O}(n) (2),
{[Cd(2)Sr(BTC)(2)(H(2)O)(5)].H(2)O}(n) (3) and [Cd(6)Ba(3)(BTC)(3)(H(2)O)(10)](n)
(4) (H(3)BTC = 1,3,5-benzenetricarboxylic acid), synthesized from H(3)BTC and the
corresponding metal salts. Single-crystal X-ray analysis shows that compound 1 is
a three-dimensional (3D) framework based on heterometallic Cd-O-Cd-O-Mg inorganic
chain subunits, compounds 2 and 3 are basically isostructural and feature a 3D
framework based on Ca(II) or Sr(II) polyhedrons decorated with Cd-O-Cd inorganic
chains. Compound 4 is a 3D framework templated by disordered inorganic hydrate
Ba(II) ions, and also features inorganic Cd-O-Cd chains, which are connected
together through corner sharing with the {Cd(1)O(6)} polyhedrons by {Ba(1)O(6)}
polyhedrons, giving rise to a rare heterometallic 3D inorganic skeleton.
Moreover, the solid-state fluorescence of compounds 1-4 and NLO properties of
compounds 2-4 have also been investigated at room temperature.
PMID- 23154615
TI - Advances in growth factor delivery for therapeutic angiogenesis.
AB - Therapeutic angiogenesis is a new revascularization strategy involving the
administration of growth factors to induce new vessel formation. The biology and
delivery of angiogenic growth factors involved in vessel formation have been
extensively studied but success in translating the angiogenic capacity of growth
factors into benefits for vascular disease patients is still limited. This could
be attributed to issues related to patient selection, growth factor delivery
methods or lack of vessel maturation. Comprehensive understanding of the cellular
and molecular cross-talk during the different stages of vascular development is
needed for the design of efficient therapeutic strategies. The presentation of
angiogenic factors either in series or in parallel using a strategy that mimics
physiological events, such as concentration and spatio-temporal profiles, is an
immediate requirement for functional blood vessel formation. This review provides
an overview of the recent delivery strategies of angiogenic factors and discusses
targeting neovascular maturation as a promising approach to induce stable and
functional vessels for therapeutic angiogenesis.
PMID- 23154616
TI - Maternal serum soluble endoglin at 30-33 weeks in the prediction of preeclampsia.
AB - OBJECTIVE: To investigate the potential value of maternal serum concentration of
soluble endoglin (sEng) at 30-33 weeks' gestation in the prediction of
preeclampsia (PE) developing at or after 34 weeks. METHODS: Serum sEng was
measured at 11-13 and at 30-33 weeks' gestation in a case-control study of 50
cases that developed PE at or after 34 weeks and 250 unaffected controls.
Regression analysis was used to determine which of the factors amongst the
maternal characteristics were significant predictors of first- and third
trimester log10 sEng in the control group. The measured values of sEng were
converted into multiples of the unaffected median (MoM) and the MoM values in the
PE and controls were compared. RESULTS: The median sEng MoM at 30-33 weeks was
significantly higher in the PE group (1.39, IQR 0.94-2.18) than in the controls
(0.95, IQR 0.77-1.19), but at 11-13 weeks there was no significant difference
between the groups. In screening by a combination of maternal characteristics and
third-trimester sEng, the detection rates of intermediate- and late-PE, at a
false-positive rate of 10%, were 64.3 and 50.0%, respectively. CONCLUSION:
Screening by maternal characteristics and sEng at 30-33 weeks could identify most
pregnancies that will subsequently develop PE.
PMID- 23154617
TI - Bee venom at different concentrations modulates the aeroallergen-induced
activation of nasal polyp epithelial cells.
AB - Bee venom (BV) has long been used as an oriental traditional medicine for the
control of pain and inflammation. However, BV's anti-inflammatory mechanisms
remain unclear. This study aimed to clarify the potential clinical efficacy of BV
concerning the anti-inflammatory effect on nasal epithelial cell inflammation.
Nasal polyp epithelial cells were obtained from patients. Cells were exposed to
Alternaria alternata, Aspergillus nigra, Dermatophagoides pteronyssinus,
Dermatophagoides farina and lipopolysaccharide with or without various
concentrations of BV. Interleukin (IL)-6, IL-8, and granulocyte macrophage colony
stimulating factor were measured to determine the activation of epithelial cells.
Nuclear factor-KB (NF-KB) and activator protein 1 expression and activity were
determined with Western blot analysis and ELISA. Cytotoxicity of BV was measured
using a CellTiter-96(r) aqueous cell proliferation assay kit. Cell survival was
significantly decreased at BV concentrations exceeding 5 ug/ml. Fungi-induced
cytokine production was more effectively inhibited by BV than house dust mite.
Alternaria enhanced NF-KB expression, which was strongly inhibited by BV. BV
appears to be relatively safe, and is of potential value for the treatment of
airway inflammation and/or immunologic diseases.
PMID- 23154618
TI - Semantic localization-driven partial image retrieval in CT series.
AB - BACKGROUND: Picture archiving and communication systems (PACS) contain very large
amounts of computed tomography (CT) data. When querying a PACS for a particular
series, the user is often not interested in the complete series but in a certain
region of interest (ROI), described e.g. by an example view in another series or
an anatomical concept. OBJECTIVES: Restricting a retrieval query to such an ROI
saves both loading time and navigational effort. In this paper, we propose an
efficient method for defining and retrieving ROIs. METHODS: We employ
interpolation and regression techniques for mapping the slices of a series to a
newly generated standardized height atlas of the human body. RESULTS:
Examinations of the accuracy and the saved input/output (I/O) costs of our new
method on a repository of 1,360 CT series demonstrate the advantages of our
system. Depending on the scope of the retrieval query, we can economize up to 99%
of the total loading time. CONCLUSION: Our proposed method for flexible, context
based, partial image retrieval enables the user to directly focus on the relevant
portion of the image material and it targets the high potential of I/O cost
reduction of a common PACS.
PMID- 23154620
TI - Microfibrillar-associated protein 5 is linked with markers of obesity-related
extracellular matrix remodeling and inflammation.
AB - OBJECTIVE: Microfibrillar-associated protein 5 (MFAP5) is an extracellular matrix
(ECM) glycoprotein, which is colocalized with microfibrils in elastin networks.
Its function in adipose tissue (AT) is not known. We have recently shown that the
expression of MFAP5 is downregulated in AT along with weight reduction (WR) in
persons with metabolic syndrome (MetS). The aim of this work was to study whether
the change of MFAP5 mRNA expression in response to WR is associated with markers
of adiposity, glucose metabolism and insulin resistance in human AT. DESIGN:
Weight reduction intervention study in parallel study design (The Genobin study).
Altogether 46 obese subjects with impaired glucose tolerance and features of MetS
were randomized to a WR (n=28) or a control group (n=18) lasting for 33 weeks.
MEASUREMENTS: Circulating glucose and insulin concentrations were measured and
subcutaneous AT biopsies were performed before and after the intervention. The
mRNA expression was studied by quantitative real-time PCR (QPCR). RESULTS: QPCR
of human AT biopsy samples confirmed that MFAP5 is highly expressed in AT and its
expression is decreased during WR. The mRNA expression of MFAP5 correlated
positively with body mass index, and the change in MFAP5 mRNA expression during
WR correlated positively with the change of body fat mass. Furthermore, the MFAP5
mRNA expression correlated negatively with circulating fasting concentrations of
adiponectin and interleukin (IL)-1beta and positively with leptin, insulin and IL
1Ra levels. In addition, the MFAP5 mRNA expression correlated positively with the
mRNA expressions of peroxisome proliferator-activated receptor gamma, cyclin D2
and A disintegrin and metalloproteinase domain 12, genes involved in AT
remodeling. CONCLUSION: This study demonstrates that MFAP5 is highly expressed in
human AT and is correlated with markers of insulin resistance. Furthermore, it is
possible that MFAP5 is related to ECM remodeling during development of obesity.
PMID- 23154619
TI - Current and emerging quantitative magnetic resonance imaging methods for
assessing and predicting the response of breast cancer to neoadjuvant therapy.
AB - Reliable early assessment of breast cancer response to neoadjuvant therapy (NAT)
would provide considerable benefit to patient care and ongoing research efforts,
and demand for accurate and noninvasive early-response biomarkers is likely to
increase. Response assessment techniques derived from quantitative magnetic
resonance imaging (MRI) hold great potential for integration into treatment
algorithms and clinical trials. Quantitative MRI techniques already available for
assessing breast cancer response to neoadjuvant therapy include lesion size
measurement, dynamic contrast-enhanced MRI, diffusion-weighted MRI, and proton
magnetic resonance spectroscopy. Emerging yet promising techniques include
magnetization transfer MRI, chemical exchange saturation transfer MRI, magnetic
resonance elastography, and hyperpolarized MR. Translating and incorporating
these techniques into the clinical setting will require close attention to
statistical validation methods, standardization and reproducibility of technique,
and scanning protocol design.
PMID- 23154621
TI - Adaptive-weighted total variation minimization for sparse data toward low-dose x
ray computed tomography image reconstruction.
AB - Previous studies have shown that by minimizing the total variation (TV) of the to
be-estimated image with some data and other constraints, piecewise-smooth x-ray
computed tomography (CT) can be reconstructed from sparse-view projection data
without introducing notable artifacts. However, due to the piecewise constant
assumption for the image, a conventional TV minimization algorithm often suffers
from over-smoothness on the edges of the resulting image. To mitigate this
drawback, we present an adaptive-weighted TV (AwTV) minimization algorithm in
this paper. The presented AwTV model is derived by considering the anisotropic
edge property among neighboring image voxels, where the associated weights are
expressed as an exponential function and can be adaptively adjusted by the local
image-intensity gradient for the purpose of preserving the edge details. Inspired
by the previously reported TV-POCS (projection onto convex sets) implementation,
a similar AwTV-POCS implementation was developed to minimize the AwTV subject to
data and other constraints for the purpose of sparse-view low-dose CT image
reconstruction. To evaluate the presented AwTV-POCS algorithm, both qualitative
and quantitative studies were performed by computer simulations and phantom
experiments. The results show that the presented AwTV-POCS algorithm can yield
images with several notable gains, in terms of noise-resolution tradeoff plots
and full-width at half-maximum values, as compared to the corresponding
conventional TV-POCS algorithm.
PMID- 23154622
TI - Effects of a fixed combination of losartan with hydrochlorothiazide on glucose
tolerance in hypertensive patients uncontrolled with angiotensin ii receptor
blockers alone.
AB - AIM: The concomitant use of angiotensin II receptor blocker (ARB) with low doses
of hydrochlorothiazide (HCTZ) may provide additional antihypertensive activity.
HCTZ induces hypokalemia and hyperglycemia, while ARB slightly induces
hyperkalemia. Recently, it has been reported that ARB/ HCTZ did not worsen
fasting blood sugar levels; however, the detailed glucose tolerance change effect
with combination therapy of ARB/HCTZ compared to ARB alone therapy remains to be
investigated. METHODS: Treated non-diabetes mellitus (DM) hypertensive patients
taking a common dose of ARB regimens, not achieving blood pressure (BP) goals,
were switched to 50 mg Losartan/12.5 mg HCTZ combinations, and the 75 g oral
glucose tolerance test (75 g OGTT) was performed before switching and after
switching at 3 months. RESULTS: This study included 30 patients aged 66.5+/-8.7
years, 67% women. Pre-switching BP 146.6+/-17.0/ 88.4+/-10.4 mmHg decreased and
was maintained at a steady state, reaching 131.4+/-1.0/73.8+/-8.8 mmHg (p<0.001)
3 months later. After switching, blood glucose levels on the 75 g OGTT at
fasting, 30, 60 and 120 minutes were significantly decreased. Homeostasis model
assessment as an index of insulin resistance and the whole body insulin
sensitivity index were significantly ameliorated. CONCLUSIONS: On the 75 g OGTT,
50 mg Losartan with 12.5 mg HCTZ combinations did not worsen glucose tolerance;
moreover, they improved BP, insulin resistance and sensitivity in non-DM Japanese
patients with essential hypertension uncontrolled with ARBs alone.
PMID- 23154623
TI - Milestones in genetics of structural skin disorders.
PMID- 23154624
TI - The complexity of elastic fiber biogenesis: the paradigm of cutis laxa.
PMID- 23154625
TI - Heritable ectopic mineralization disorders: the paradigm of pseudoxanthoma
elasticum.
PMID- 23154626
TI - Molecular heterogeneity of blistering disorders: the paradigm of epidermolysis
bullosa.
PMID- 23154627
TI - Heritable filaggrin disorders: the paradigm of atopic dermatitis.
PMID- 23154629
TI - Next-generation diagnostics for genodermatoses.
PMID- 23154628
TI - Genetics of structural hair disorders.
AB - The identification of causative genes carries the promise of new and innovative
therapeutic strategies for both inherited and acquired hair disorders. Moreover,
the delineation of the relationships between similar phenotypes, resulting from
mutations affecting seemingly distinct regulatory pathways, paves the way to
improved diagnosis and treatment. Finally, understanding the biological processes
governing HF development and maintenance may have implications for more general
disease processes in the skin, such as inflammation and cancer.
PMID- 23154630
TI - Molecular therapeutics for heritable skin diseases.
PMID- 23154631
TI - Heritable collagen disorders: the paradigm of the Ehlers-Danlos syndrome.
PMID- 23154632
TI - The prion protein family: looking outside the central nervous system.
AB - Although the pivotal implication of the host-encoded Prion protein, PrP, in the
neuropathology of transmissible spongiform encephalopathy is known for decades,
its biological role remains mostly elusive. Genetic inactivation is one way to
assess such issue but, so far, PrP-knockout mice did not help much. However,
recent reports involving (1) further studies of these mice during embryogenesis,
(2) knockdown experiments in Zebrafish and (3) knockdown of Shadoo, a protein
with PrP-like functional domains, in PrP-knockout mice, all suggested a role of
the Prion protein family in early embryogenesis. This view is challenged by the
recent report that PrP/Shadoo knockout mice are healthy and fertile. Although
puzzling, these apparently contradictory data may on the contrary help at
deciphering the Prion protein family role through focusing scientific attention
outside the central nervous system and by helping the identification of other
loci involved in the genetic robustness associated with PrP.
PMID- 23154633
TI - Proteolytic clearance of extracellular alpha-synuclein as a new therapeutic
approach against Parkinson disease.
AB - Many neurodegenerative diseases such as Alzheimer disease and Parkinson disease
show similar characteristics. They typically show deposits of protein aggregates,
the formation of which is considered important in their pathogenesis. Recently,
aggregation-prone proteins have been shown to spread between cells and so may
contribute to the pathogenesis of diseases like prion disease. Such a
pathogenesis pathway is possibly common to many neurodegenerative diseases. If
confirmed, it could allow the development of therapeutic interventions against
many such diseases. In Parkinson disease, alpha-synuclein, a major component of
cytosolic protein inclusions named Lewy body, has been shown to be released and
taken up by cells, which may facilitate its progressive pathological spreading
between cells. Accordingly, inhibition of spreading by targeting extracellular
alpha-synuclein may represent a new therapy against Parkinson disease. Research
into the intercellular spreading of extracellular protein aggregations of alpha
synuclein and its clearance pathway are reviewed here with a focus on the
proteolytic clearance pathway as a therapeutic target for the treatment of
Parkinson disease. Considering the similar characteristics of aggregation-prone
proteins, these clearance systems might allow treatment of other
neurodegenerative diseases beyond Parkinson disease.
PMID- 23154634
TI - Cis phosphorylated tau as the earliest detectable pathogenic conformation in
Alzheimer disease, offering novel diagnostic and therapeutic strategies.
AB - After protein phosphorylation on certain serine or threonine residues preceding a
proline (pSer/Thr-Pro), the function of certain phosphorylated protein is further
regulated by cis-trans conformational change. Due to the lack of any tool to
detect such two conformations in cells, however, it is not even known whether any
cis or trans conformation exists in vivo, not to mention their conformation
specific functions or regulation. We developed a novel peptide chemistry
technology to generate the first pair of antibodies that can distinguish cis from
trans pThr231-Pro tau. Cis, but not trans, pThr231-tau appears early in mild
cognitive impairment (MCI) neurons and further accumulates in only degenerating
neurons as Alzheimer disease (AD) progresses, localizing to dystrophic neurites,
which are known to correlate well with memory loss. Unlike trans p-tau, the cis
cannot promote microtubule assembly, and is more resistant to dephosphorylation
and degradation and more prone to aggregation. Pin1 accelerates cis to trans
isomerization to prevent tau pathology in AD. Thus, during MCI and AD
development, cis pThr231-Pro tau is the earliest detectable pathogenic tau
conformation and antibodies and vaccines against the pathogenic cis p-tau may be
used for the early diagnosis and treatment of AD. These findings offer in vivo
approach to study conformational regulation of Pro-directed phosphorylation
signaling.
PMID- 23154636
TI - The Mozart effect on task performance in a laparoscopic surgical simulator.
AB - The Mozart Effect is a phenomenon whereby certain pieces of music induce
temporary enhancement in "spatial temporal reasoning." To determine whether the
Mozart Effect can improve surgical performance, 55 male volunteers (mean age =
20.6 years, range = 16-27), novice to surgery, were timed as they completed an
activity course on a laparoscopic simulator. Subjects were then randomized for
exposure to 1 of 2 musical pieces by Mozart (n = 21) and Dream Theater (n = 19),
after which they repeated the course. Following a 15-minute exposure to a
nonmusical piece, subjects were exposed to one of the pieces and performed the
activity course a third time. An additional group (n = 15) that was not
corandomized performed the tasks without any exposure to music. The percent
improvements in completion time between 3 successive trials were calculated for
each subject and group means compared. In 2 of the tasks, subjects exposed to the
Dream Theater piece achieved approximately 30% more improvement (26.7 +/- 8.3%)
than those exposed to the Mozart piece (20.2 +/- 7.8%, P = .021) or to no music
(20.4 +/- 9.1%, P = .049). Distinct patterns of covariance between baseline
performance and subsequent improvement were observed for the different musical
conditions and tasks. The data confirm the existence of a Mozart Effect and
demonstrate for the first time its practical applicability. Prior exposure to
certain pieces may enhance performance in practical skills requiring spatial
temporal reasoning.
PMID- 23154635
TI - Cellular prion protein and Alzheimer disease: link to oligomeric amyloid-beta and
neuronal cell death.
AB - Soluble oligomeric amyloid-beta (Abeta) has been suggested to impair synaptic and
neuronal function, leading to neurodegeneration that is clinically observed as
the memory and cognitive dysfunction characteristic of Alzheimer disease, while
the precise mechanism(s) whereby oligomeric Abeta causes neurotoxicity remains
unknown. Recently, the cellular prion protein (PrP (C) ) was reported to be an
essential co-factor in mediating the neurotoxic effect of oligomeric Abeta. Our
recent study showed that Prnp (-/-) mice are resistant to the neurotoxic effect
of oligomeric Abeta in vivo and in vitro. Furthermore, application of an anti-PrP
(C) antibody or PrP (C) peptide was able to block oligomeric Abeta-induced
neurotoxicity. These findings demonstrate that PrP (C) may be involved in
neuropathologic conditions other than conventional prion diseases, i.e.,
Creutzfeldt-Jakob disease.
PMID- 23154637
TI - miR-133a regulates vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1), a
key protein in the vitamin K cycle.
AB - Regulation of key proteins by microRNAs (miRNAs) is an emergent field in
biomedicine. Vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1) is a
relevant molecule for cardiovascular diseases, since it is the target of oral
anticoagulant drugs and plays a role in soft tissue calcification. The objective
of this study was to determine the influence of miRNAs on the expression of
VKORC1. Potential miRNAs targeting VKORC1 mRNA were searched by using online
algorithms. Validation studies were carried out in HepG2 cells by using miRNA
precursors; direct miRNA interaction was investigated with reporter assays. In
silico studies identified two putative conserved binding sites for miR-133a and
miR-137 on VKORC1 mRNA. Ex vivo studies showed that only miR-133a was expressed
in liver; transfection of miRNA precursors of miR-133a in HepG2 cells reduced
VKORC1 mRNA expression in a dose-dependent manner, as assessed by quantitative
reverse transcriptase-polymerase chain reaction (qRT-PCR) as well as protein
expression. Reporter assays in HEK293T cells showed that miR-133a interacts with
the 3'UTR of VKORC1. Additionally, miR-133a levels correlated inversely with
VKORC1 mRNA levels in 23 liver samples from healthy subjects. In conclusion, miR
133a appears to have a direct regulatory effect on expression of VKORC1 in
humans; this regulation may have potential importance for anticoagulant therapy
or aortic calcification.
PMID- 23154638
TI - Adeno-associated virus serotype 8 (AAV8) delivery of recombinant A20 to skeletal
muscle reduces pathological activation of nuclear factor (NF)-kappaB in muscle of
mdx mice.
AB - Duchenne muscular dystrophy (DMD) is a genetic muscle disease caused by the
absence of a functional dystrophin protein. Lack of dystrophin protein disrupts
the dystrophin-glycoprotein complex causing muscle membrane instability and
degeneration. One of the secondary manifestations resulting from lack of
functional dystrophin in muscle tissue is an increased level of cytokines that
recruit inflammatory cells, leading to chronic upregulation of the nuclear factor
(NF)-kappaB. Negative regulators of the classical NF-kappaB pathway improve
muscle health in the mdx mouse model for DMD. We have previously shown in vitro
that a negative regulator of the NF-kappaB pathway, A20, plays a role in muscle
regeneration. Here, we show that overexpression of A20 by using a muscle-specific
promoter delivered with an adeno-associated virus serotype 8 (AAV8) vector to the
mdx mouse decreases activation of the NF-kappaB pathway in skeletal muscle.
Recombinant A20 expression resulted in a reduction in number of fibers with
centrally placed nuclei and a reduction in the number of T cells infiltrating
muscle transduced with the AAV8-A20 vector. Taken together, we conclude that
overexpression of A20 in mdx skeletal muscle provides improved muscle health by
reduction of chronic inflammation and muscle degeneration. These results suggest
A20 is a potential therapeutic target to ameliorate symptoms of DMD.
PMID- 23154640
TI - The use of 18F-fluoromethylcholine PET/CT in differentiating focal nodular
hyperplasia from hepatocellular adenoma: a prospective study of diagnostic
accuracy.
AB - INTRODUCTION: Diagnosis of focal nodular hyperplasia (FNH) and hepatocellular
adenoma (HCA) using conventional imaging techniques can be difficult; however, it
is important to differentiate between them as these benign liver tumors require
different therapeutic strategies. The aim of our study was to prospectively
evaluate the use of PET/computed tomography (CT) with F-fluoromethylcholine (F
FCH) as a novel diagnostic approach in the differentiation between HCA and FNH.
MATERIALS AND METHODS: Fifty-six consecutive patients with a suspicion of one or
multiple HCAs or FNHs larger than 2 cm were prospectively included after written
informed consent was obtained from them. All the patients underwent a PET/CT with
F-FCH. Histopathology of the lesions was the standard of reference. The ratio of
the standardized uptake value (SUV) of the lesions compared with normal liver
uptake within the same patient was calculated. Statistical tests were evaluated
at the 95% confidence interval. RESULTS: Forty-nine patients with 60 lesions and
histopathological diagnosis of FNH or HCA completed the study and were analyzed.
The mean SUV ratio for FNH was 1.67+/-0.31 (mean+/-SD, n=28), resulting in a
positive likelihood ratio of 32.3 for PET-positive FNH. The mean SUV ratio for
HCA was 0.82+/-0.17 (n=32), with a likelihood ratio of ~100 for PET-negative HCA.
Receiver operating characteristic curve analysis revealed an optimal SUV ratio
cutoff value of 1.13, which reached 100% sensitivity and 97% specificity in
differentiating FNH from HCA. CONCLUSION: This prospective study shows that
PET/CT with F-FCH can accurately differentiate FNH from HCA and may become a
valuable diagnostic tool when conventional imaging techniques fail to do so.
PMID- 23154639
TI - STAT1, STAT6 and adenosine 3',5'-cyclic monophosphate (cAMP) signaling drive
SOCS3 expression in inactive ulcerative colitis.
AB - Ulcerative colitis (UC) is a chronic disease associated with long periods of
quiescent disease followed by fulminant exacerbation. Imminent relapse in UC is
associated with high mucosal expression of suppressor of cytokine signaling 3
(SOCS3); hence, knowledge of the mechanisms driving mucosal SOCS3 expression may
provide important clues as to rational therapy. Thus, here we aim to characterize
the molecular forces driving SOCS3 expression in the mucosal compartment,
focusing on druggable pathways. The colon epithelial cell line Caco-2 was
stimulated with interferon (IFN)-gamma, interleukin (IL)-4 or prostaglandin E(2)
(PGE(2)) to allow correlations between SOCS3 expression with signal transducer
and activator of transcription 1 (STAT1), STAT6 and adenosine 3',5'-cyclic
monophosphate (cAMP) signaling, respectively. The physiological relevance of the
findings obtained was assessed by immunohistochemical staining for the activated
forms of STAT1, STAT6, protein kinase A (PKA)-Cgamma and cAMP response element
binding protein (CREB) in biopsies from inactive UC patients and controls.
Stimulation with IFN-gamma, IL-4 or PGE(2) induced activation of STAT1, STAT6 and
cAMP, respectively, in colonic cells, without any signs of concomitant STAT3
activation. Forced activation of all these signaling pathways was sufficient for
SOCS3 expression. Biopsies from patients with inactive UC showed significant
increase of phosphorylated STAT1 (p-STAT1) (p < 0.0001), p-STAT6 (p = 0.0001), p
PKA-Cgamma (p = 0.0003) and p-CREB (p = 0.0025) expression compared with
controls. STAT3-independent SOCS3 induction in inactive UC involves multiple
proinflammatory signaling pathways and contradicts the usefulness of pathway
specific antiinflammatory drugs for preventing relapse. Our findings suggest that
broad-spectrum antiinflammatory drugs are essential to counteract increases in
SOCS3 expression and exacerbation of disease. Our results highlight the
multifactorial nature of the factors that cause exacerbation in UC.
PMID- 23154641
TI - Quantitative carbon ion beam radiography and tomography with a flat-panel
detector.
AB - High dose gradients are inherent to ion beam therapy. This results in high
sensitivity to discrepancies between planned and delivered dose distributions.
Therefore an accurate knowledge of the ion stopping power of the traversed tissue
is critical. One proposed method to ensure high quality dose deposition is to
measure the stopping power by ion radiography. Although the idea of imaging with
highly energetic ions is more than forty years old, there is a lack of simple
detectors suitable for this purpose. In this study the performance of an
amorphous silicon flat-panel detector, originally designed for photon imaging,
was investigated for quantitative carbon ion radiography and tomography. The flat
panel detector was exploited to measure the water equivalent thickness (WET) and
water equivalent path length (WEPL) of a phantom at the Heidelberg Ion-Beam
Therapy Center (HIT). To do so, the ambiguous correlation of detector signal to
particle energy was overcome by active or passive variation of carbon ion beam
energy and measurement of the signal-to-beam energy correlation. The active
method enables one to determine the WET of the imaged object with an uncertainty
of 0.5 mm WET. For tomographic WEPL measurements the passive method was exploited
resulting in an accuracy of 0.01 WEPL. The developed imaging technique presents a
method to measure the two-dimensional maps of WET and WEPL of phantoms with a
simple and commercially available detector. High spatial resolution of 0.8 * 0.8
mm(2) is given by the detector design. In the future this powerful tool will be
used to evaluate the performance of the treatment planning algorithm by studying
WET uncertainties.
PMID- 23154642
TI - The predictive significance of neurocognitive factors for functional outcome in
bipolar disorder.
AB - PURPOSE OF REVIEW: Poor psychosocial functioning in bipolar disorder often
persists even after affective symptom remission. Cognitive deficits, which have
emerged as a core feature of bipolar disorder in the past few years, are among
the factors implicated in adverse psychosocial outcomes of patients suffering
from bipolar disorder. This review aims to overview recent literature on the
association of neurocognition and psychosocial functioning in bipolar disorder.
RECENT FINDINGS: Cognitive deficits (mainly general neurocognitive functioning,
attention and verbal learning and memory) are important determinants of poor
psychosocial functioning in bipolar disorder, although to a lesser extent than in
schizophrenia. Although affective symptoms appear to be a more important
predictor of functional outcome in symptomatic patients, cognitive deficits also
play a significant role, more readily recognizable in euthymic or chronic
patients. SUMMARY: Given the importance of cognitive impairments for psychosocial
outcomes in bipolar disorder, the development of interventions targeting
cognitive impairments is imperative for improving recovery rates and quality of
life in patients, even after adequate symptom control.
PMID- 23154643
TI - Novel biomarkers in major depression.
AB - PURPOSE OF REVIEW: This article reviews literature published over the period
January 2011-June 2012 on biomarkers in major depression. RECENT FINDINGS:
Although a large body of research accumulated over the past decades points to
distinct biological mechanisms being involved in the pathophysiology of major
depressive disorder (MDD), its precise pathobiology is not yet fully understood.
In the last 2 years, substantial new research has been generated in an attempt to
identify and characterize novel candidate biomarkers for MDD. This review
provides an update on biomarker research in MDD and summarizes the most recent
results from neuroimaging, genetic, epigenetic, and neurochemical studies in MDD.
SUMMARY: Promising new findings report high diagnostic accuracy for metabonomic
and epigenetic approaches as well as combinatorial functional neuroimaging
approaches, which are currently representing the forefront of MDD biomarker
development.
PMID- 23154645
TI - Complex posttraumatic stress disorder and survivors of human rights violations.
AB - PURPOSE OF REVIEW: This article reviews recent findings on Complex Posttraumatic
Stress Disorder (CPTSD) and proposes future research which would help to
establish the nature of CPTSD in relation to Posttraumatic Stress Disorder
(PTSD). RECENT FINDINGS: Research on survivors of torture and war has found that
CPTSD can occur when there is no history of childhood abuse. fMRI studies appear
to highlight differences in neural activity in individuals exhibiting primary
dissociation compared with individuals exhibiting secondary dissociation.
Research has begun to show that, when symptoms of secondary dissociation are
appropriately managed, exposure-based therapies are an effective treatment for
individuals with CPTSD. SUMMARY: Much research on CPTSD has emphasized its
developmental basis and the disruptive effects of trauma in childhood and
adolescence on subsequent emotional development. However, some studies on
survivors of torture in adult life identify similar symptom patterns, despite
there being no history of childhood trauma. It is argued that comparative
research is required between victims of developmental trauma (such as childhood
sexual abuse) and victims who experienced prolonged interpersonal trauma in
adulthood (such as torture), as this could be useful in establishing the cause of
CPTSD and in delineating clinically and therapeutically meaningful subtypes. It
is also proposed that a focus on underlying neurobiological processes would help
in developing and refining CPTSD as a construct and informing treatment.
PMID- 23154644
TI - The expanding evidence base for rTMS treatment of depression.
AB - PURPOSE OF REVIEW: Daily left prefrontal transcranial magnetic stimulation (TMS)
for several weeks was first proposed as an acute treatment for depression in the
early 1990s, and was Food and Drug Administration (FDA) approved in 2008. In the
past year, several important studies have been published that extend our
understanding of this novel treatment approach. RECENT FINDINGS: The first round
of multisite clinical trials with TMS addressed whether prefrontal rTMS has
efficacy and were conducted in carefully selected depressed patients who were
antidepressant medication free. Several more recent studies assess the clinical
effectiveness of TMS and report that about 35-40% of real-world patients who are
commonly taking adjunctive antidepressants reach remission with a modest side
effect profile. There are also new studies examining the durability of the TMS
induced antidepressant effect. Fifty-eight percent of TMS remitters remain
remitted at 3-month follow-up. SUMMARY: These recent studies suggest that daily
left prefrontal TMS over several weeks as a treatment for depression not only
appears to have efficacy in rigorous randomized controlled trials, but is
effective in real-world settings, with remission in 30-40% of patients. The TMS
antidepressant effect, once achieved, appears to be as durable as with other
antidepressant medications or interventions. Much more research is needed,
particularly with issues such as the TMS coil location, stimulation intensity and
frequency, and dosing strategy.
PMID- 23154646
TI - Identification of pediatric brain neoplasms using Raman spectroscopy.
AB - PURPOSE: Raman spectroscopy can quickly and accurately diagnose tissue in near
real-time. This study evaluated the capacity of Raman spectroscopy to diagnose
pediatric brain tumors. EXPERIMENTAL DESIGN: Samples of untreated pediatric
medulloblastoma (4 samples and 4 patients), glioma (i.e. astrocytoma,
oligodendroglioma, ependymoma, ganglioglioma and other gliomas; 27 samples and 19
patients), and normal brain samples (33 samples and 5 patients) were collected
fresh from the operating room or from our frozen tumor bank. Samples were divided
and tested using routine pathology and Raman spectroscopy. Twelve Raman spectra
were collected per sample. Support vector machine analysis was used to classify
spectra using the pathology diagnosis as the gold standard. RESULTS: Normal brain
(321 spectra), glioma (246 spectra) and medulloblastoma (82 spectra) were
identified with 96.9, 96.7 and 93.9% accuracy, respectively, when compared with
each other. High-grade ependymomas (41 spectra) were differentiated from low
grade ependymomas (25 spectra) with 100% sensitivity and 96.0% specificity.
Normal brain tissue was distinguished from low-grade glioma (118 spectra) with
91.5% sensitivity and 97.8% specificity. For these analyses, the tissue-level
classification was determined to be 100% accurate. CONCLUSION: These results
suggest Raman spectroscopy can accurately distinguish pediatric brain neoplasms
from normal brain tissue, similar tumor types from each other and high-grade from
low-grade tumors.
PMID- 23154647
TI - Towards a personalized and dynamic CRT-D. A computational cardiovascular model
dedicated to therapy optimization.
AB - BACKGROUND: In spite of cardiac resynchronization therapy (CRT) benefits, 25-30%
of patients are still non responders. One of the possible reasons could be the
non optimal atrioventricular (AV) and interventricular (VV) intervals settings.
Our aim was to exploit a numerical model of cardiovascular system for AV and VV
intervals optimization in CRT. METHODS: A numerical model of the cardiovascular
system CRT-dedicated was previously developed. Echocardiographic parameters,
Systemic aortic pressure and ECG were collected in 20 consecutive patients before
and after CRT. Patient data were simulated by the model that was used to optimize
and set into the device the intervals at the baseline and at the follow up. The
optimal AV and VV intervals were chosen to optimize the simulated selected
variable/s on the base of both echocardiographic and electrocardiographic
parameters. RESULTS: Intervals were different for each patient and in most cases,
they changed at follow up. The model can well reproduce clinical data as verified
with Bland Altman analysis and T-test (p > 0.05). Left ventricular remodeling was
38.7% and left ventricular ejection fraction increasing was 11% against the 15%
and 6% reported in literature, respectively. CONCLUSIONS: The developed numerical
model could reproduce patients conditions at the baseline and at the follow up
including the CRT effects. The model could be used to optimize AV and VV
intervals at the baseline and at the follow up realizing a personalized and
dynamic CRT. A patient tailored CRT could improve patients outcome in comparison
to literature data.
PMID- 23154648
TI - Associations of proteinuria, fluid volume imbalance, and body mass index with
circadian ambulatory blood pressure in chronic kidney disease patients.
AB - BACKGROUND/AIMS: Obesity and hypervolemic status are the main causes of
hypertension in patients with chronic kidney disease (CKD). However, it is
difficult to differentiate between them. We aimed to assess the associations of
body mass index (BMI) and total body water (TBW) with ambulatory blood pressure
(ABP). METHODS: Body composition by bioelectrical impedance analysis (BIA) and 24
h ABP were measured in 40 patients with CKD. TBW was assessed using corrected
TBWBIA adjusted for body surface area (cTBWBIA) and the TBWBIA/TBWWatson ratio
obtained using an anthropometric formula (Watson). RESULTS: Elevated ABP (average
24-h BP >= 135/85 mmHg) was noted in 23 patients, who were more likely to have a
higher cTBWBIA and TBWBIA/TBWWatson ratio than patients without elevated BP.
Patients with nocturnal non-dipping (<10% drop in BP during sleep) were more
likely to have a higher TBWBIA/TBWWatson ratio. Proteinuria and the
TBWBIA/TBWWatson ratio were significant independent factors for 24-h ABP. BMI had
a positive correlation with the cTBWBIA, TBWBIA/TBWWatson ratio and furosemide
use. CONCLUSION: Hypertension is dependent on proteinuria and fluid volume
imbalance. The TBWBIA/TBWWatson ratio can serve as an indicator of fluid volume
dependent hypertension. BMI is affected by TBW, in which case BMI can become less
involved with 24-h ABP.
PMID- 23154649
TI - How I would manage a man with COPD who has few symptoms and is at low risk of an
exacerbation: a primary care perspective from Australia.
PMID- 23154650
TI - How I would manage a woman with COPD who is symptomatic but at low risk of an
exacerbation: a primary care perspective from the UK.
PMID- 23154651
TI - How I would manage a woman with COPD with few symptoms but at high risk of an
exacerbation: a primary care perspective from Spain.
PMID- 23154652
TI - How I would manage a man with COPD who is symptomatic and at high risk of an
exacerbation: a primary care perspective from Norway.
PMID- 23154653
TI - Serologic screening for herpes simplex virus type 2 in persons with human
immunodeficiency virus.
AB - Screening for subclinical herpes simplex virus type 2 (HSV-2) may be a useful
adjunct in human immunodeficiency virus (HIV) care. However, HSV-2 serological
tests have been suggested to perform less well in HIV-infected populations. In
this study, HerpeSelect HSV-2 ELISA was compared with the Sure-Vue Rapid HSV-2
Test for HSV-2 screening of sera from 310 HIV-infected persons receiving care at
an HIV-dedicated clinic in the Southeastern United States. In the study, assay
agreement and whether the performance of both tests, rather than 1 test alone,
would improve screening accuracy were determined. Overall percent test agreement
was 96%. Negative percent agreement was best at a HerpeSelect index value <0.90
and positive percent agreement was best at a HerpeSelect index value >=3.0 (97%
and 100%, respectively). Using the manufacturer's established cutoffs for a
HerpeSelect positive test result versus negative test result, discordant results
between assays occurred in 4% of the cases, and the majority of these cases
occurred when the HerpeSelect index value was between 0.9 and 2.9. These data
suggest a good correlation between the HerpeSelect and the Sure-Vue HSV-2 Rapid
Test in a U.S. HIV-infected population and suggest that confirmatory testing may
not help in HSV-2 diagnosis except in cases where HerpeSelect index values are
between 0.9 and 3.0.
PMID- 23154654
TI - Management of elderly and frail elderly cancer patients: the importance of
comprehensive geriatrics assessment and the need for guidelines.
AB - OBJECTIVES: Management of elderly and frail patients with cancer is complex and
requires a multidisciplinary approach. This article reviews and discusses the
current literature that evaluates the relevance of comprehensive geriatrics
assessment (CGA) and other evaluation tools in the detection of this vulnerable
patient population. METHODS: A literature search of articles in English, Spanish
and Portuguese was conducted in PubMed through September 2011. RESULTS: There is
lack of detailed information concerning the efficacy, tolerability and toxicity
of cancer therapies in senior adults, although the literature indicates that
there is a trend toward including elderly patients and their outcome. Recent
guidelines advocate a careful patient selection through a CGA. For vulnerable
(pre-frail) and frail elderly cancer patients, there is no consensus in relation
to selection and type of treatments. CGA has been advocated as the gold standard
for evaluation of elderly patients, but thorough evaluation of vulnerable and
frail patients has not been undertaken. A tool to evaluate vulnerable elderly
patients to predict treatment outcomes is also needed. DISCUSSION: The adoption
of the CGA in oncology practice has been slow because of the difficulties with
practicality and objectivity. A shorter reliable tool for rapid and complete
assessment is needed. Inclusion of frail elderly patients in treatment trials is
recommended. New treatment approaches for frail elderly cancer patients need to
be further investigated. Some studies that used serum markers of frailty found
that even in the absence of clinical signs, some elderly patients might be
already vulnerable. A potential cancer frailty index also needs further
investigation.
PMID- 23154655
TI - Statin-mediated low-density lipoprotein lowering in chronic congestive heart
failure.
AB - Many theories and clinical trials have attempted to address the effect of low
density lipoprotein (LDL) lowering in chronic congestive heart failure (CHF). The
current evidence suggests that there is no convincing reason for administering
statins to patients with nonischemic heart failure. Although they do not reduce
the mortality rate, statins reduce LDL cholesterol and may provide some benefit
to patients with ischemic heart failure. In contrast, some authors believe that
statin therapy may actually worsen outcomes in patients with CHF, especially if
there is excessive reduction in LDL cholesterol. This review discusses the
theories attempting to link the adverse effects of statin-mediated LDL lowering
in CHF to increased levels of endotoxin or reduced levels of coenzyme Q10. In
addition, the 2 largest randomized, double-blind, placebo-controlled clinical
trials (CORONA and GISSI-HF) were discussed. It is clear that more trials are
needed to definitely ascertain the effect of statins on CHF.
PMID- 23154656
TI - New evidence of neuroprotection by lactate after transient focal cerebral
ischaemia: extended benefit after intracerebroventricular injection and efficacy
of intravenous administration.
AB - BACKGROUND: Lactate protects mice against the ischaemic damage resulting from
transient middle cerebral artery occlusion (MCAO) when administered
intracerebroventricularly at reperfusion, yielding smaller lesion sizes and a
better neurological outcome 48 h after ischaemia. We have now tested whether the
beneficial effect of lactate is long-lasting and if lactate can be administered
intravenously. METHODS: Male ICR-CD1 mice were subjected to 15-min suture MCAO
under xylazine + ketamine anaesthesia. Na L-lactate (2 ul of 100 mmol/l) or
vehicle was administered intracerebroventricularly at reperfusion. The
neurological deficit was evaluated using a composite deficit score based on the
neurological score, the rotarod test and the beam walking test. Mice were
sacrificed at 14 days. In a second set of experiments, Na L-lactate (1 umol/g
body weight) was administered intravenously into the tail vein at reperfusion.
The neurological deficit and the lesion volume were measured at 48 h. RESULTS:
Intracerebroventricularly injected lactate induced sustained neuroprotection
shown by smaller neurological deficits at 7 days (median = 0, min = 0, max = 3, n
= 7 vs. median = 2, min = 1, max = 4.5, n = 5, p < 0.05) and 14 days after
ischaemia (median = 0, min = 0, max = 3, n = 7 vs. median = 3, min = 0.5, max =
3, n = 7, p = 0.05). Reduced tissue damage was demonstrated by attenuated
hemispheric atrophy at 14 days (1.3 +/- 4.0 mm(3), n = 7 vs. 12.1 +/- 3.8 mm(3),
n = 5, p < 0.05) in lactate-treated animals. Systemic intravenous lactate
administration was also neuroprotective and attenuated the deficit (median = 1,
min = 0, max = 2.5, n = 12) compared to vehicle treatment (median = 1.5, min = 1,
max = 8, n = 12, p < 0.05) as well as the lesion volume at 48 h (13.7 +/- 12.2
mm(3), n = 12 vs. 29.6 +/- 25.4 mm(3), n = 12, p < 0.05). CONCLUSIONS: The
beneficial effect of lactate is long-lasting: lactate protects the mouse brain
against ischaemic damage when supplied intracerebroventricularly during
reperfusion with behavioural and histological benefits persisting 2 weeks after
ischaemia. Importantly, lactate also protects after systemic intravenous
administration, a more suitable route of administration in a clinical emergency
setting. These findings provide further steps to bring this physiological,
commonly available and inexpensive neuroprotectant closer to clinical translation
for stroke.
PMID- 23154657
TI - Ferromagnetic coupling and spin canting behaviour in heterobimetallic
Re(IV)M(II/III) (M = Co(II/III), Ni(II)) species.
AB - Three novel heterobimetallic Re(IV) compounds of formulae [ReBr(4)(MU-ox)M(4,7
Cl(2)phen)(2)].CH(3)CN.CH(3)NO(2) [M = Co(II) (1) and Ni(II) (2)] and
[ReBr(4)(ox)](3)[Co(III)(5,6-dmphen)(3)](2).CH(3)CN.2CH(3)NO(2).4H(2)O (3) [ox =
oxalate, 4,7-Cl(2)phen = 4,7-dichloro-1,10-phenanthroline and 5,6-dmphen = 5,6
dimethyl-1,10-phenanthroline] have been synthesised and the structures of 1 and 3
determined by single crystal X-ray diffraction. Compound 1 is an oxalato-bridged
Re(IV)Co(II) heterodinuclear complex where the [ReBr(4)(ox)](2-) unit acts as a
bidentate ligand towards the [Co(4,7-Cl(2)phen)(2)](2+) entity, the separation
between Re(IV) and Co(II) across the oxalate being 5.482(1) A. Compound 3 is an
ionic salt whose structure is made up of [Re(IV)Br(4)(ox)](2-) anions and
[Co(III)(5,6-dmphen)(3)](3+) cations plus acetonitrile, nitromethane and water as
solvent molecules. The magnetic properties of 1-3 were investigated in the
temperature range 1.9-300 K. Relatively large ferromagnetic interactions between
Re(IV) and M(II) through the bis(bidentate) oxalato occur in 1 and 2 [J(ReM) =
+11.0 (1) and +12.2 cm(-1) (2), the Hamiltonian being defined as H =
J(ReM)S(Re).S(M)] which are explained on the basis of orbital symmetry
considerations. A behaviour typical of a magnetically diluted Re(IV) complex with
a large and positive value of zero-field splitting for the ground level (D(Re) =
+43 cm(-1)) is observed for 3 in the high temperature range, whereas it exhibits
spin canting in the low temperature domain as well as magnetic ordering below ca.
4.8 K.
PMID- 23154658
TI - Correlative studies on the effects of obesity, diabetes and hypertension on gene
expression in omental adipose tissue of obese women.
AB - OBJECTIVE: A major consequence of obesity is the enormous expansion of and
enhanced inflammatory response seen in visceral adipose tissue. I hypothesized
that the expression of inflammatory markers in visceral omental fat would
correlate with the extent of visceral adiposity as measured by waist
circumference or body mass index and that diabetes and hypertension, defined as
subjects taking anti-hypertensive drugs, would be associated with changes in mRNA
expression in visceral fat. DESIGN AND METHODS: The expression of 106 mRNAs by RT
PCR was examined in observational studies using extracts of omental fat of obese
women undergoing bariatric surgery as well as the circulating levels of some
adipokines. We also compared the mRNA levels of 65 proteins in omental fat
removed during gastric bypass surgery of women with and without hypertension and
those with type 2 diabetes. RESULTS: Out of 106 mRNAs the expression of 10 mRNAs
in omental fat of women not taking anti-hypertensive drugs correlated with waist
circumference while 7 different mRNAs had significant correlations with
circulating glucose. The correlations of waist circumference with mRNA expression
were abolished, except for interleukin (IL)-1 receptor antagonist (IL-1RA), in
women taking anti-hypertensive drugs. The correlations of blood glucose with
omental fat mRNA expression were abolished, except for that of Akt1 and Akt2, in
women taking anti-hypertensive drugs. However, the expression of 4 different
mRNAs in omental fat was affected by circulating glucose in subjects taking anti
hypertensive drugs. The circulating levels of IL-1 RA, but not fatty acid binding
protein 4, adipsin and phospholipase A2, correlated with both waist circumference
and mRNA expression in omental fat. CONCLUSION: In female bariatric surgery
patients, the mRNA expression of some proteins in omental fat was affected by the
degree of obesity, whereas hypertension and diabetes affected a separate set of
mRNAs.Nutrition and Diabetes (2011) 1, e17; doi:10.1038/nutd.2011.14; published
online 26 September 2011.
PMID- 23154659
TI - Qualitative analysis of naturalistic decision making in adults with chronic heart
failure.
AB - BACKGROUND: Self-care of heart failure has been described as a naturalistic
decision-making process, but the data available to defend this description are
anecdotal. OBJECTIVES: The aim of this study was to explore the process used by
adults with chronic heart failure to make decisions about their symptoms.
METHODS: This was a secondary analysis of data obtained from four mixed methods
studies. The full data set held qualitative data on 120 adults over the age of 18
years. For this analysis, maximum variation sampling was used to purposively
select a subset of 36 of the qualitative interviews to reanalyze. RESULTS: In
this sample, equally distributed by gender, 56% Caucasian, between 40 and 98
years, the overarching theme was that decisions about self-care reflect a
naturalistic decision-making process with components of situation awareness with
mental simulation of a plausible course of action and an evaluation of the
outcome of the action. In addition to situation awareness and mental simulation,
three key factors were identified as influencing self-care decision making: (a)
experience; (b) decision characteristics such as uncertainty, ambiguity, high
stakes, urgency, illness, and involvement of others in the decision-making
process; and (c) personal goals. DISCUSSION: These results support naturalistic
decision making as the process used by this sample of adults with heart failure
to make decisions about self-care.
PMID- 23154660
TI - Endothelial dysfunction, macrophage infiltration and NADPH oxidase-dependent
superoxide production were attenuated by erythropoietin in streptozotocin-induced
diabetic rat aorta.
AB - Erythropoietin (EPO) has been used for the management of renal anemia. Recent
studies suggest the pleiotropic properties of EPO in various tissues such as
brain, kidney and vasculature. Diabetes mellitus is a major risk for development
of vascular impairment. The aim of the present study was to investigate the
hypothesis that EPO would be beneficial in inhibiting diabetic macroangiopathy.
Recombinant human EPO (rHuEPO; 150 U/kg, 3 times/week, s.c.) was administered to
streptozotocin-induced diabetic rats for 4 weeks. Streptozotocin (65 mg/kg, i.v.)
significantly increased macrophage infiltration and adhesion molecules, monocyte
chemoattractant protein-1 and osteopontin mRNA levels in the aorta. These
inflammatory changes were suppressed by rHuEPO. Vasodilation in response to
acetylcholine in the aortic ring was impaired in the diabetic rats, and improved
by rHuEPO. rHuEPO inhibited the aortic expression of mRNA for nicotinamide
adenine dinucleotide phosphate (NADPH) oxidase and the NADPH oxidase-dependent
superoxide production and the increase in plasma malondialdehyde concentration in
diabetic rats. rHuEPO also decreased the level of the receptor for advanced
glycation end products in the aorta. We also found an increased expression of
phospho-Akt and endothelial nitric oxide synthase and plasma NOx level in the
rHuEPO-treated group. On the other hand, rHuEPO did not affect blood glucose
levels, hemoglobin A(1c), blood pressure or hematocrit in diabetic rats. These
results indicate that rHuEPO exerts pleiotropic antioxidant and anti-inflammatory
properties in diabetic rat aorta.
PMID- 23154662
TI - Ceramic gentamicin beads in vascular graft infection--a cautionary note.
PMID- 23154663
TI - Hysteroscopic inspection and total curettage are insufficient for discriminating
endometrial cancer from atypical endometrial hyperplasia.
AB - Endometrial cancer (EC) is the most prevalent gynecologic malignancy in Japan.
Atypical endometrial hyperplasia (AEH) is viewed as the premalignant lesion of
EC, however it is often difficult to distinguish EC from AEH. The rate of
concurrent EC in women diagnosed preoperatively with AEH based on endometrial
biopsy was reported as 17-52%. Although hysteroscopic inspection and total
curettage are considered as useful methods to make diagnosis of endometrial
lesions, there is no report using this combined method to discriminate EC from
AEH. The purpose of this study was to examine whether hysteroscopic inspection
and total curettage improve the prevalence of EC among women diagnosed
preoperatively with AEH. We reviewed 22 patients who underwent hysteroscopic
inspection and total curettage and were diagnosed with AEH before undergoing
hysterectomy between November 2001 and May 2011. The diagnosis made with the
hysterectomy specimens revealed AEH in 10 patients (45.5%), endometrial
hyperplasia without atypia in 3 (13.6%), and endometrioid adenocarcinoma, the
most common type of EC, in 9 (40.9%). Endometrioid adenocarcinoma included 7
patients without myometrial invasion (31.8%) and 2 patients with superficial
myometrial invasion (9.1%). There was no hysteroscopic finding that was specific
for EC or AEH. In conclusion, about 41% of women who underwent hysterectomy
under a diagnosis of AEH were found to have coexisting adenocarcinoma, although
the prevalence of EC among those women was similar to that in earlier reports
with endometrial biopsy. Accordingly, we must be careful in planning the
therapeutic strategy for women with a preoperative diagnosis of AEH.
PMID- 23154665
TI - Current world literature.
PMID- 23154664
TI - Experimental estimation of the photons visiting probability profiles in time
resolved diffuse reflectance measurement.
AB - A time-gated intensified CCD camera was applied for time-resolved imaging of
light penetrating in an optically turbid medium. Spatial distributions of light
penetration probability in the plane perpendicular to the axes of the source and
the detector were determined at different source positions. Furthermore, visiting
probability profiles of diffuse reflectance measurement were obtained by the
convolution of the light penetration distributions recorded at different source
positions. Experiments were carried out on homogeneous phantoms, more realistic
two-layered tissue phantoms based on the human skull filled with Intralipid-ink
solution and on cadavers. It was noted that the photons visiting probability
profiles depend strongly on the source-detector separation, the delay between the
laser pulse and the photons collection window and the complex tissue composition
of the human head.
PMID- 23154667
TI - Gold nanorod-covered kanamycin-loaded hollow SiO2 (HSKAu(rod)) nanocapsules for
drug delivery and photothermal therapy on bacteria.
AB - A hybrid bactericidal material, gold nanorod-covered kanamycin-loaded hollow
SiO(2) (HSKAu(rod)) nanocapsules, is constructed. The hybrid material combines
the features of a chemical drug with photothermal physical sterilization which
decreases the dosage of broad-spectrum antibiotic and the physical damage of
biological systems. Hollow SiO(2) nanocapsules are used as carriers for drug
delivery. The nanocapsules load a model drug, kanamycin, and are covered with
gold nanorods to avoid drug leakage and realize photothermal treatment. The
sterilizing effect on the bacterial strain is investigated by incubating E. coli
BL21 with the hybrid nanocapsules and irradiating under near-infrared light (NIR)
for 20 min. A bactericidal effect, i.e., a sterilizing rate of 53.47%, is
achieved for the HSKAu(rod) nanocapsules under NIR irradiation, with respect to a
net sum sterilizing rate of 34.49% for the individual components of the
HSKAu(rod) nanocapsules, e.g., carrier nanocapsules, chemical sterilization of
kanamycin and physical sterilization due to the gold nanorods under NIR
irradiation. It is demonstrated that the combination of chemical drug and
physical sterilization results in an obvious synergistic effect and makes the
sterilization more effective. This novel hybrid has great potential as an
adjuvant therapeutic alternative material for sterilization or even for the
control of disease.
PMID- 23154668
TI - Medical thoracoscopy in multiloculated and organised empyema.
PMID- 23154669
TI - Accuracy of signs of clinical chorioamnionitis in the term parturient.
AB - OBJECTIVE: Uniform histopathologic guidelines were applied to diagnose
chorioamnionitis and estimate the accuracy of clinical signs in term parturients.
STUDY DESIGN: A retrospective cohort study utilized slides from term parturient
placentas with Amniotic Fluid Infection Nosology Committee guidelines as the gold
standard. Sensitivity, specificity and accuracy for fever, maternal tachycardia
and fetal tachycardia were calculated. RESULT: Of 641 placentas, 367 (57.3%) had
histologic chorioamnionitis and 274 (42.7%) were negative. Fever had a
sensitivity of 42%, specificity of 86.5% and accuracy of 61%. Fever, maternal
tachycardia and fetal tachycardia had a sensitivity of 18.3%, specificity of
98.2% and accuracy of 52.4%. CONCLUSION: Histologic chorioamnionitis, frequently
asymptomatic, is a common finding in placentas examined from term parturients.
Clinical signs are not accurate in the diagnosis. Adoption of uniform pathologic
guidelines will facilitate research into the clinical significance of these
lesions in the future.
PMID- 23154670
TI - Passive cooling during transport of asphyxiated term newborns.
AB - OBJECTIVE: To evaluate the efficacy and safety of passive cooling during
transport of asphyxiated newborns. STUDY DESIGN: Retrospective medical record
review of newborns with perinatal asphyxia transported for hypothermia between
July 2007 and June 2010. RESULT: Of 43 newborns transported, 27 were passively
cooled without significant adverse events. Twenty (74%) passively cooled newborns
arrived with temperature between 32.5 and 34.5 degrees C. One newborn arrived
with a temperature <32.5, and 6 (22%) had temperatures >34.5 degrees C. Time
from birth to hypothermia was significantly shorter among passively cooled
newborns compared with newborns not cooled (215 vs 327 min, P<0.01), even though
time from birth to admission to Boston Children's Hospital was similar (252 vs
259 min, P=0.77). Time from birth to admission was the only significant predictor
of increased time to reach target temperature (P=0.001). CONCLUSION: Exclusive
passive cooling achieves significantly earlier initiation of effective
hypothermia for asphyxiated newborns but should not delay transport for active
cooling.
PMID- 23154671
TI - Arthroscopic treatment of fragmented coronoid process with severe elbow
incongruity. Long-term follow-up in eight Bernese Mountain Dogs.
AB - The purpose of this study was to investigate the long-term treatment results of
fragmented coronoid process (FCP) in joints with a radio-ulnar step greater than
3 mm. Treatment of these patients only consisted of fragment removal, without
correction of the incongruity. The eight Bernese Mountain Dogs (11 joints)
included in this study showed obvious clinical signs of elbow disease and were
diagnosed with severe elbow incongruity and concomitant FCP in the time period
from 1999-2003. At that time, elbow radiography, computed tomography, and
arthroscopy were performed. The mean follow-up period was 5.6 years. The follow
up consisted of a telephone questionnaire combined with a clinical and
radiographic re-evaluation at our clinic. The questionnaire revealed that all
dogs were either free of lameness or only lame following heavy exercise. One dog
sporadically required medication after heavy exercise. The owner satisfaction
rate was 100%. The clinical re-evaluation did not reveal any signs of pain or
lameness in all cases. Range-of- motion was decreased in nine of the 11 elbows.
Radiographs revealed an increase in severity of osteoarthritis in every case.In
this case series, arthroscopic fragment removal without treatment of incongruity
was demonstrated to be a valuable treatment option and may provide a satisfactory
long-term outcome.
PMID- 23154672
TI - VAP-1, a novel molecule linked to endothelial damage and kidney function in
kidney allograft recipients.
AB - BACKGROUND/AIMS: VAP-1 (vascular adhesion protein-1) is a copper-containing SSAO
(semicarbazide sensitive amine oxidase) secreted by vascular smooth muscle cells,
adipocytes, endothelial cells with functional monoamine oxidase activity. The
oxidation process generates harmful products that may be involved in
atherosclerosis and vascular damage. Elevation of SSAO activity is observed in
atherosclerosis, diabetes mellitus and obesity. On the other hand, renalase, with
possible monoamine oxidase activity, which breaks down catecholamines like SSAO,
is also expressed in the endothelium as well as in the kidney. The aim of the
study was to assess VAP-1 levels and its correlations with endothelial injury
markers and renalase in 50 kidney allograft recipients. METHODS: Hemoglobin,
urea, creatinine, rate were studied by standard laboratory method in the hospital
central laboratory. We assessed markers of endothelial function/injury: vWF,
thrombomodulin, ICAM, VCAM, CD40L, CD44, CD146, inflammation: hsCRP, and IL-6 and
adipocytokines: leptin, adiponectin, visfatin, apelin with commercially available
assays. RESULTS: The mean serum VAP-1 in Tx was significantly higher comparing to
the control group. In kidney transplant recipients VAP-1 correlated with BMI
(r=0.39, p<0.01), CD44 (r=0.27, p<0.05), hsCRP (r=0.28, p<0.05), serum creatinine
(r=0.29, p<0.05), eGFR (CKD-EPI formula r=-0.27, p<0.05, MDRD r=-0.27,p<0.05,
Cockcroft-Gault r=-0.35,p<0.01), serum urea (r=0.27, p<0.05), CD146 (r=0.49,
p<0.001), CD40L (r=0.26, p<0.06), and renalase (r=0.34, p<0.05). In multiple
regression analysis VAP-1 was predicted 80% by serum creatinine (beta value 0.33,
p=0.01), and CD146 (beta value 43, p=0.0005). CONCLUSION: VAP-1, elevated in
kidney transplant recipients, is predominantly dependent on endothelial damage
and kidney function, which deteriorated with time after kidney transplantation.
PMID- 23154673
TI - Increased incidence of cardiovascular disease: are low-carbohydrate-high-protein
diets truly to blame?
PMID- 23154674
TI - HIV consensus guideline recommends antiretroviral treatment regardless of CD4
count, new regimens and possible regimen change for chronic low level viraemia.
PMID- 23154675
TI - Creating a bio-hybrid signal transduction pathway: opening a new channel of
communication between cells and machines.
AB - Manipulation of signal transduction pathways presents a viable mechanism to
interface cells with electronics. In this work, we present a two-step signal
transduction pathway involving cellular and electronic transduction elements. In
order to circumvent many of the conventional difficulties encountered when
harnessing chemical signalling for the purpose of electronics communication,
gaseous nitric oxide (NO) was selected as the signalling molecule. By genetic
engineering of the nitric oxide synthase protein eNOS and insertion of light
oxygen-voltage (LOV) domains, we have created a photoactive version of the
protein. The novel chimeric eNOS was found to be capable of producing NO in
response to excitation by visible light. By coupling these mutant cells to a
surface modified platinum electrode, it was possible to convert an optical signal
into a chemical one, followed by subsequent conversion of the chemical signal
into an electrical output.
PMID- 23154676
TI - Staffing matters-every shift: data from the Military Nursing Outcomes Database
can be used to demonstrate that the right number and mix of nurses prevent
errors.
AB - OVERVIEW: Data from the Military Nursing Outcomes Database (MilNOD) project
demonstrate that inadequately staffed shifts can increase the likelihood of
adverse events, such as falls with injury, medication errors, and needlestick
injuries to nurses. Such evidence can be used to show that it takes not only the
right number of nursing staff on every shift to ensure safe patient care, but
also the right mix of expertise and experience. Based on findings from the MilNOD
project, the authors present realistic scenarios of common dilemmas hospitals
face in nurse staffing, illustrating the potential hazards for patients and
nurses alike.
PMID- 23154677
TI - Missing incidents in community-dwelling people with dementia: understanding how
these dangerous events differ from dementia-related 'wandering' is critical to
assessment, intervention, and prevention.
AB - OVERVIEW: At every stage of dementia, people with the condition are at risk for
both missing incidents, in which they are unattended and unable to navigate a
safe return to their caregiver, and "wandering," a term often used to describe
repetitive locomotion with patterns such as lapping or pacing. By understanding
the differences between these two phenomena, nurses can teach caregivers how to
anticipate and prevent missing incidents, which are not necessarily related to
wandering. The authors differentiate missing incidents from wandering, describe
personal characteristics that may influence the outcomes in missing incidents,
and suggest strategies for preventing and responding to missing incidents.
PMID- 23154678
TI - Secondary spacer modulated assembly of polyoxometalate based metal-organic
frameworks.
AB - To investigate the influence of a secondary spacer on the resulting structures of
POMOFs containing pytz, five new compounds with different dimensionalities,
[Cu(5)(2-pytz)(6)(H(2)O)(4)][SiMo(12)O(40)].3H(2)O (1), [Cu(3)(2
pytz)(4)bipy][H(2)SiMo(12)O(40)].bipy (2), [Cu(3)(2
pytz)(2)(bipy)(4)(H(2)O)(6)][H(4)SiW(12)O(40)](2).6H(2)O (3), [Cu(2)(2
pytz)(phen)(OH)](2)[SiW(12)O(40)].H(2)O (4), [Cu(3)(4
pytz)(4)(H(2)O)(4)][H(2)SiW(12)O(40)].2H(2)O (5), were synthesized. When only 2
pytz was employed, compound 1 with a 3D framework was obtained, whereas when the
secondary spacers (4,4'-bipy, phen and 4-pytz) were introduced into the reaction
system of 1, compounds 2-5 were obtained and exhibit a broad range of structures,
including 0D, 1D, 2D and 3D frameworks. It can be observed from the architectures
of compounds 1-5 that the secondary spacers have a great effect on the structures
of the MOFs, which results in the formation of various dimensional POMOF
compounds. Additionally, photocatalytic experiments of 1-5 for the photocatalytic
degradation of RhB under UV irradiation were also investigated.
PMID- 23154679
TI - Stearic acid content of abdominal adipose tissues in obese women.
AB - OBJECTIVE: Subcutaneous (SC) adipose tissue stearic acid (18:0) content and
stearoyl-CoA desaturase-1 (SCD1)-mediated production of oleic acid (18:1) have
been suggested to be altered in obesity. The objective of our study was to
examine abdominal adipose tissue fatty acid content and SCD1 mRNA/protein level
in women. SUBJECTS AND METHODS: Fatty acid content was determined by capillary
gas chromatography in SC and omental (OM) fat tissues from two subgroups of 10
women with either small or large OM adipocytes. Samples from 10 additional women
were used to measure SCD1 mRNA and protein expression, total extracellular signal
regulated kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 protein as well as
insulin receptor (IR) expression levels. RESULTS: OM fat 18:0 content was
significantly lower in women with large OM adipocytes compared with women who had
similar adiposity, but small OM adipocytes (2.37+/-0.45 vs 2.75+/-0.30 mg per 100
g adipose tissue, respectively, P?0.05). OM fat 18:0 content was negatively
related to the visceral adipose tissue area (r=-0.44, P=0.05) and serum
triglyceride levels (r=-0.56, P<0.05), while SC fat 18:0 content was negatively
correlated with total body fat mass (BFM) (r=-0.48, P<0.05) and fasting insulin
concentration (r=-0.73, P<0.005). SC adipose tissue desaturation index
(18:1/18:0), SCD1 expression and protein levels were positively correlated with
BFM. Moreover, obese women were characterized by a reduced OM/SC ratio of SCD1
mRNA and protein levels. A similar pattern was observed for ERK1/2 and IR
expression. CONCLUSION: The presence of large adipocytes and increased adipose
mass in a given fat compartment is related to reduced 18:0 content and increased
desaturation index in women, independently of dietary fat intake. The depot
specific difference in ERK1/2 expression and activation, as well as in SCD1 and
IR expression in obese women is consistent with the hypothesis that they may
predominantly develop SC fat, which could in turn help protect from metabolic
disorders.
PMID- 23154680
TI - Proximal correlates of metabolic phenotypes during 'at-risk' and 'case' stages of
the metabolic disease continuum.
AB - OBJECTIVE: To examine the social and behavioural correlates of metabolic
phenotypes during 'at-risk' and 'case' stages of the metabolic disease continuum.
DESIGN: Cross-sectional study of a random population sample. PARTICIPANTS: A
total of 718 community-dwelling adults (57% female), aged 18-92 years from a
regional South Australian city. MEASUREMENTS: Total body fat and lean mass and
abdominal fat mass were assessed by dual energy x-ray absorptiometry. Fasting
venous blood was collected in the morning for assessment of glycated haemoglobin,
plasma glucose, serum triglycerides, cholesterol lipoproteins and insulin. Seated
blood pressure (BP) was measured. Physical activity and smoking, alcohol and diet
(96-item food frequency), sleep duration and frequency of sleep disordered
breathing (SDB) symptoms, and family history of cardiometabolic disease,
education, lifetime occupation and household income were assessed by
questionnaire. Current medications were determined by clinical inventory.
RESULTS: 36.5% were pharmacologically managed for a metabolic risk factor or had
known diabetes ('cases'), otherwise were classified as the 'at-risk' population.
In both 'at-risk' and 'cases', four major metabolic phenotypes were identified
using principal components analysis that explained over 77% of the metabolic
variance between people: fat mass/insulinemia (FMI); BP; lipidaemia/lean mass
(LLM) and glycaemia (GLY). The BP phenotype was uncorrelated with other
phenotypes in 'cases', whereas all phenotypes were inter-correlated in the 'at
risk'. Over and above other socioeconomic and behavioural factors, medications
were the dominant correlates of all phenotypes in 'cases' and SDB symptom
frequency was most strongly associated with FMI, LLM and GLY phenotypes in the
'at-risk'. CONCLUSION: Previous research has shown FMI, LLM and GLY phenotypes to
be most strongly predictive of diabetes development. Reducing SDB symptom
frequency and optimising the duration of sleep may be important concomitant
interventions to standard diabetes risk reduction interventions. Prospective
studies are required to examine this hypothesis.
PMID- 23154681
TI - Abdominal adiposity and daily step counts as determinants of glycemic control in
a cohort of patients with type 2 diabetes mellitus.
AB - OBJECTIVE: Favorable effects of walking levels on glycemic control have been
hypothesized to be mediated through reductions in abdominal adiposity, but this
has not been well studied. We addressed this issue in patients treated for type 2
diabetes. DESIGN: Cross-sectional analysis. SUBJECTS: A total of 201 subjects
with type 2 diabetes underwent assessments of pedometer-measured daily step
counts, blood pressure, A1C and anthropometric measures (2006-2010). Associations
of anthropometric indicators of abdominal adiposity (that is, waist
circumference; waist-to-hip ratio (WHR)) with A1C were evaluated through linear
regression models adjusting for age, ethnicity, sex and the use of insulin and
oral hypoglycemic agents. Models including waist circumference were additionally
adjusted for body mass index (BMI). A similar approach was used to examine A1C
and daily step associations. RESULTS: Among the 190 subjects (mean age 60 years;
mean BMI 30.4 kg m(-2)), mean values (s.d.) for waist circumference and WHR were
respectively, 99.1 cm (13.3) and 0.88 (0.07) in women, and 104.5 cm (13.1) and
0.97 (0.06) in men. Mean A1C and daily step count were respectively, 7.6% (1.4)
and 5 338 steps per day (2609), and were similar for both sexes.There was a 0.51%
(95% confidence interval (CI): 0.10, 0.93) A1C increment per s.d. increase in
waist circumference and a 0.32% (95% CI: 0.08, 0.56) A1C increment per s.d.
increase in WHR in fully adjusted models. Each s.d. increase in daily step count
was associated with clinically significant reductions in waist circumference and
BMI. Each s.d. increase in daily steps was associated with a 0.21% (95% CI: 0.02,
0.41) A1C decrement that declined to 0.16% (95% CI: -0.35, 0.04) with further
adjustment for anthropometric indicators of abdominal adiposity. CONCLUSION:
Higher daily steps may be associated with lower A1C values both directly and via
changes in abdominal adiposity.
PMID- 23154683
TI - Wheat-derived arabinoxylan oligosaccharides with prebiotic effect increase
satietogenic gut peptides and reduce metabolic endotoxemia in diet-induced obese
mice.
AB - BACKGROUND: Alterations in the composition of gut microbiota -known as dysbiosis-
have been proposed to contribute to the development of obesity, thereby
supporting the potential interest of nutrients acting on the gut microbes to
produce beneficial effect on host energetic metabolism. Non-digestible
fermentable carbohydrates present in cereals may be interesting nutrients able to
influence the gut microbiota composition. OBJECTIVE AND DESIGN: The aim of the
present study was to test the prebiotic potency of arabinoxylan oligosaccharides
(AXOS) prepared from wheat bran in a nutritional model of obesity, associated
with a low-grade chronic systemic inflammation. Mice were fed either a control
diet or a high fat (HF) diet, or a HF diet supplemented with AXOS during 8 weeks.
RESULTS: AXOS supplementation induced caecal and colon enlargement associated
with an important bifidogenic effect. It increased the level of circulating
satietogenic peptides produced by the colon (peptide YY and glucagon-like peptide
1), and coherently counteracted HF-induced body weight gain and fat mass
development. HF-induced hyperinsulinemia and the Homeostasis Model Assessment of
insulin resistance were decreased upon AXOS feeding. In addition, AXOS reduced HF
induced metabolic endotoxemia, macrophage infiltration (mRNA of F4/80) in the
adipose tissue and interleukin 6 (IL6) in the plasma. The tight junction proteins
(zonula occludens 1 and claudin 3) altered upon HF feeding were upregulated by
AXOS treatment suggesting that the lower inflammatory tone was associated with
the improvement of gut barrier function. CONCLUSION: Together, these findings
suggest that specific non-digestible carbohydrates produced from cereals such as
AXOS constitute a promising prebiotic nutrient in the control of obesity and
related metabolic disorders.
PMID- 23154684
TI - Treating the small airways.
AB - The final article in this series evaluates the approaches undertaken to treating
the small-airway region of the lungs and the clinical implications of inhaled
therapy targeting the periphery in patients with asthma and chronic obstructive
pulmonary disease.
PMID- 23154685
TI - Challenges in child and adolescent psychiatric education.
PMID- 23154682
TI - Appetite regulation and weight control: the role of gut hormones.
AB - The overwhelming increase in the prevalence of overweight and obesity in recent
years represents one of the greatest threats to the health of the developed
world. Among current treatments, however, gastrointestinal (GI) surgery remains
the only approach capable of achieving significant weight loss results with long
term sustainability. As the obesity prevalence approaches epidemic proportions,
the necessity to unravel the mechanisms regulating appetite control has garnered
significant attention. It is well known that physical activity and food intake
regulation are the two most important factors involved in body weight control. To
regulate food intake, the brain must alter appetite. With this realization has
come increased efforts to understand the intricate interplay between gut hormones
and the central nervous system, and the role of these peptides in food intake
regulation through appetite modulation. This review discusses the central
mechanisms involved in body weight regulation and explores a suite of well
characterized and intensely investigated anorexigenic and orexigenic gut
hormones. Their appetite-regulating capabilities, post-GI surgery physiology and
emerging potential as anti-obesity therapeutics are then reviewed.
PMID- 23154686
TI - Family therapy: the neglected core competence.
PMID- 23154687
TI - Guidelines for the general psychiatry application process and for inter-residency
transitions.
PMID- 23154688
TI - Promoting scholarship during child and adolescent psychiatry residency.
AB - BACKGROUND: In 2003, the Institute of Medicine (IOM) drew attention to the
critical national shortage of psychiatrist-researchers and the need for
competency-based curricula to promote research training during psychiatry
residency as one way to address this shortage at the institutional level. Here,
the authors report on the adaptation, implementation, and results attained with a
broadly applicable, developmental, competency-based framework for promoting
scholarship during child and adolescent psychiatry residency. METHODS: The
authors instituted structural program changes, protecting time for all residents
to engage in scholarly pursuits and a mentorship program to support residents in
their scholarly interests. The authors assessed five graduating classes before
and five classes after these changes were implemented, examining whether these
changes sustained scholarship for residents with previous experience during
general psychiatry residency and whether they promoted emergence of new
scholarship among residents without such experience. RESULTS: The authors
observed a tenfold increase in the number of residents engaged in rigorously
defined scholarly pursuits after the program changes, which helped sustain the
scholarship of more residents with previous experience and promoted the emergence
of more new scholarship among residents without previous experience. CONCLUSION:
The authors conclude that it is possible to sustain and promote scholarship
during child psychiatry residency despite the relatively short duration of the
program and the many requirements for graduation and certification. The changes
implemented were universal in scope and required no special funding mechanisms,
making this approach potentially exportable to other training programs.
PMID- 23154689
TI - Family therapy training in child and adolescent psychiatry fellowship programs.
AB - OBJECTIVE: This study describes the current state of family therapy training in a
sample of child and adolescent psychiatry fellowship programs. METHOD: Child and
adolescent psychiatry fellows (N=66) from seven training programs completed a
questionnaire assessing demographics, family therapy training experiences, common
models of treatment and supervision, attitudes about family therapy, and
perspectives on clinical training and clinical skill. RESULTS: Fellows ascribed a
high degree of importance to family therapy skills, yet most had not seen more
than one outpatient family with family therapy supervision during their training.
They identified structural family therapy and family psychoeducation as the
primary family treatment orientations in their programs. CONCLUSION: Although
child psychiatry fellows believed that strong family therapy skills would benefit
their patients, most had limited supervised experiences with families. Child and
adolescent psychiatry training programs appear to offer exposure to family
therapy without sufficient opportunities to develop proficiency. The author
discusses educational implications for child and adolescent psychiatry.
PMID- 23154690
TI - Reflective team supervision after a frightening event on a psychiatric crisis
service.
AB - OBJECTIVE: The authors demonstrate the value of reflective team supervision as
part of the informal curriculum in an emergency psychiatry setting after a
potentially traumatizing adverse event. METHOD: The article gives a case
presentation of a violent adolescent who eloped from his hospital Emergency
Department and provides a description of team supervision sessions that
facilitated informal learning for residents and medical students after this
event. RESULTS: Reflective team supervision sessions after this event resulted
both in improved resident well-being and learning opportunities, as well as
hospital quality improvement designed to prevent future elopements. CONCLUSIONS:
Reflective team supervision can be an essential component of trainee education to
enhance residents' well-being and to promote both systems-based practice and
practice-based learning. This can be an excellent forum to explore themes of
humility, self-reflection, and professional growth.
PMID- 23154692
TI - Medical students' comfort with pregnant women with substance-use disorders: a
randomized educational study.
AB - OBJECTIVE: The study objective was to determine whether medical students'
attendance at a rehabilitation residence for pregnant women with substance-use
disorders yielded changes in their attitudes and comfort levels in providing care
to this population. METHODS: This randomized educational trial involved 96
consecutive medical students during their obstetrics and gynecology clerkship. In
addition to attending a half-day prenatal clinic designed for women with
substance-use disorders, every student was randomly assigned either to attend
(Study group) or not to attend (Control group) a rehabilitation residence for
pregnant women with substance-use disorders. The primary objective was to measure
differences in responses to a confidential 12-question survey addressing comfort
levels and attitudes, at the beginning and end of the clerkship. RESULTS: Survey
responses revealed improvements in students' comfort levels and attitudes toward
pregnant women with substance-use disorders by attending the clinic alone or the
clinic and residence. Those who attended the residence reported becoming more
comfortable in talking with patients about adverse effects from substance abuse,
more understanding of "street" terms, and stronger belief that patients will
disclose their substance use to providers. Residents expressed more openly their
hardships and barriers while trying to set therapeutic goals. CONCLUSIONS:
Medical students became more comfortable and insightful about pregnant women with
substance-use disorders after attending a rehabilitation residence in addition to
a prenatal clinic dedicated to this population.
PMID- 23154693
TI - Improving child and adolescent psychiatry education for medical students: an
inter-organizational collaborative action plan.
AB - OBJECTIVE: A new Child and Adolescent Psychiatry in Medical Education (CAPME)
Task Force, sponsored by the Association for Directors of Medical Student
Education in Psychiatry (ADMSEP), has created an inter-organizational partnership
between child and adolescent psychiatry (CAP) educators and medical student
educators in psychiatry. This paper outlines the task force design and strategic
plan to address the long-standing dearth of CAP training for medical students.
METHOD: The CAPME ADMSEP Task Force, formed in 2010, identified common challenges
to teaching CAP among ADMSEP's CAPME Task Force members, utilizing focus-group
discussions and a needs-assessment survey. The Task Force was organized into five
major sections, with inter-organizational action plans to address identified
areas of need, such as portable modules and development of benchmark CAP
competencies. RESULTS/CONCLUSION: The authors predict that all new physicians,
regardless of specialty, will be better trained in CAP. Increased exposure may
also improve recruitment into this underserved area.
PMID- 23154694
TI - Teaching to improve parent-child interaction: an educational case study.
PMID- 23154695
TI - Teaching patient-centered care and systems-based practice in child and adolescent
psychiatry.
PMID- 23154697
TI - A four factor model of systems-based practices in psychiatry.
PMID- 23154699
TI - A biopsychosocial approach to HIV/AIDS education for psychiatry residents.
PMID- 23154700
TI - Primary treatment approaches in child and adolescent psychiatry training.
PMID- 23154702
TI - The self-directed, structured summary as a teaching tool in a psychiatry journal
club.
PMID- 23154703
TI - Do I know what I do not know? Self-evaluation of performance in student-run
seminars by psychiatry trainees in India.
PMID- 23154704
TI - Chronic pain: a psychiatrist's personal illness narrative.
PMID- 23154705
TI - Doing data-driven research in training: the experience of two residents.
PMID- 23154706
TI - Electronic evaluation forms and the rate of completion of residency evaluations.
PMID- 23154707
TI - Assessing the need for a multi-modal curriculum in psychopharmacology education.
PMID- 23154708
TI - Disease characteristics should be taken into account when comparing attitudes and
levels of stigma toward psychiatric and medical conditions.
PMID- 23154710
TI - Portrayal of psychiatric disorders: are simulated patients authentic?
PMID- 23154712
TI - Asthma in pregnancy: management strategies.
AB - PURPOSE OF REVIEW: Asthma is one of the most prevalent chronic medical conditions
to complicate pregnancy. With approximately one-third of women experiencing a
worsening of control during the course of their pregnancy, identifying those at
greatest risk has the potential to improve maternal and fetal outcomes for a
large number of pregnancies. Similarly, active management strategies that
prioritize asthma control in this vulnerable population can have a far-reaching
impact. RECENT FINDINGS: Demographic characteristics and patient noncompliance
place certain populations of pregnant women at increased risk of poor asthma
control during pregnancy. In addition, undertreatment and disparities in care of
acute exacerbations during pregnancy likely contribute. Targeted educational
interventions and treatment algorithms using objective markers of disease
activity have shown improved outcomes in asthma control. SUMMARY: Active
management strategies which focus on identifying patient-specific risk factors,
patient and provider education, and targeted treatment interventions can improve
asthma care for women during pregnancy.
PMID- 23154713
TI - A multicenter prospective observational study of triple therapy with rabeprazole,
amoxicillin and metronidazole for Helicobacter pylori in Japan.
AB - OBJECTIVE: Triple therapy with rabeprazole (RPZ), amoxicillin (AMPC) and
metronidazole (MNZ) (RPZ+AMPC+MNZ therapy: RAM therapy) has been approved by the
Japanese Ministry of Health, Labour and Welfare as a second-line therapy for
Helicobacter pylori-positive gastric and duodenal ulcers in Japan. The present
multicenter prospective observational study aimed to investigate the safety and
efficacy of RAM therapy in clinical practice. METHODS: Patients with H. pylori
positive gastric or duodenal ulcers (including ulcer scars) in whom first-line
therapy was unsuccessful were administered 10 mg of RPZ, 750 mg of AMPC and 250
mg of MNZ twice daily for seven days (total: 14 doses) based on an approved dose
and regimen. Patient background factors, including complications, previous
medical history, concomitant drugs, eradication results and adverse events were
recorded by the investigator. RESULTS: The incidence of adverse drug reactions
was 2.21% and the H. pylori eradication rate was 92.8%. Subgroup analyses
performed to investigate the patient background factors affecting safety and
efficacy revealed no factors that significantly affected the incidence of adverse
drug reactions or the H. pylori eradication rate. CONCLUSION: Amid reports of
decreased eradication rates with clarithromycin-based first-line therapy, the
>90%H. pylori eradication rate achieved in the present study demonstrates the
clinical efficacy of RAM therapy in subjects in whom first-line therapy is
unsuccessful.
PMID- 23154714
TI - Influence of glycemic variability on the HbA1c level in elderly male patients
with type 2 diabetes.
AB - OBJECTIVE: To investigate the influence of glycemic variability on the HbA1c
level in elderly male patients with type 2 diabetes (T2DM). METHODS: The 24-h
glucose profiles were obtained using a continuous glucose monitoring system in
291 elderly male type 2 diabetic patients. The relationship between the glycemic
variability and HbA1c level was assessed in these patients. RESULTS: The mean
amplitude of glycemic excursions (MAGE) in patients with HbA1c >=7.0% was
significantly higher than in patients with HbA1c <7.0% (4.33+/-1.67 vs. 3.48+/
1.46 mmol/L, p<0.001). A simple (Pearson's) correlation analysis indicated that
the MAGE was significantly correlated with the HbA1c (r=0.229, p<0.001). Compared
with the lowest quartile, the highest quartile of the MAGE was associated with a
significantly increased risk of having a HbA1c >=7.0% after multiple adjustments
(p (for trend) <0.001). CONCLUSION: The glycemic variability had a significant
influence on the HbA1c level in elderly male patients with T2DM. The present data
suggests that patients with higher glycemic variability might have higher HbA1c
levels.
PMID- 23154715
TI - The impact of a negative history of smoking on survival in patients with non
small cell lung cancer detected with clinic-based screening programs.
AB - OBJECTIVE: The aim of this study was to determine the epidemiological
characteristics of never-smoking patients with non-small cell lung cancer (NSCLC)
detected with clinic-based screening programs, focusing on clinical risk factors
and survival. METHODS: The medical records of NSCLC patients (n=285) diagnosed at
Fujisawa City Hospital between April 2000 and December 2010 with lesions that
were originally detected with clinic-based screening programs in Fujisawa City
were reviewed to identify the clinicopathological variables and survival
outcomes. RESULTS: Of the 285 NSCLC patients, 95 (33.3%) were never-smokers. A
comparison between the never-smoking and ever-smoking patients revealed that the
never-smokers included a significantly greater proportion of women and patients
with adenocarcinoma (86.3% vs. 12.6%: p<0.001 or 94.7% vs. 55.8%: p<0.001,
respectively). The overall survival rate of the never-smoking patients was
significantly superior to that of the ever-smokers (p=0.004). In addition to
smoking status, factors found to be significantly associated with the overall
survival rate in univariate analyses were gender, stage, histology and first line
treatment. A multivariate analysis revealed smoking status to be an independent
prognostic factor in addition to stage and first line treatment. CONCLUSION: The
differences in the clinicopathological factors and survival outcomes between
never-smoking and ever-smoking patients with NSCLC detected with clinic-based
screening programs suggest that persuading people to never start smoking is
important.
PMID- 23154716
TI - Postpartum migraines: a long-term prospective study.
AB - OBJECTIVE: There are many reports regarding the course of migraines during
pregnancy. However, the prevalence and characteristics of migraines during the
postpartum period have not been adequately investigated. We prospectively
investigated the patients suffering from migraines over a long postpartum period
in an obstetrics department in Japan. METHODS: We investigated the course of
migraines experienced during the postpartum period by patients in a postnatal
ward. The patients were surveyed during the first postpartum week and 1, 3, 6 and
12 months after delivery. The patients were provided a headache diary to assess
medication use and migraine attack frequency, severity (the faces pain scale) and
duration. RESULTS: The migraine remission rate was 63%, 83% and 85% during the
first, second and third trimesters, respectively. No patient experienced a
worsening of headaches during pregnancy. Headache recurrence during the first
month after delivery was more frequent in the patients >30 years of age than in
those <=30 years of age (p<0.05). The percentage of women experiencing recurrence
at 1, 3, 6 and 12 months after delivery was 63%, 75%, 78% (n=60) and 87.5%
(n=40), respectively. In breastfeeding patients, the rates were 50%, 65.8%, 71.1%
and 91.7% and in bottle feeding patients, the rates were 86.4%, 90.9%, 95.5% and
81.3%, respectively. CONCLUSION: We found that 85% of the patients with migraines
experience remission during pregnancy and that more than 50% experience
recurrence during the first month after delivery. Until six months after
delivery, breastfeeding is associated with a lower recurrence rate than bottle
feeding.
PMID- 23154717
TI - A patient with gastric adenosquamous carcinoma with intraperitoneal free cancer
cells who remained recurrence-free with postoperative S-1 chemotherapy.
AB - The case of a patient with gastric adenosquamous carcinoma with positive cancer
cells on intraperitoneal washing cytology (CY1) who achieved a long recurrence
free survival is herein reported. A 74-year-old man was found to have
adenosquamous carcinoma of the stomach. Partial gastrectomy was performed, and a
pathological examination confirmed a diagnosis of adenosquamous carcinoma with
invasion into the serosa and lymph node metastasis. S-1 monotherapy was
administered because a cytologic examination revealed that the patient's
peritoneal washings were positive for cancer cells. The patient remains alive
with no recurrence two years and 10 months after undergoing surgery.
Postoperative chemotherapy with S-1 monotherapy is effective for treating
adenosquamous carcinoma of the stomach with CY1 and might contribute to long-term
survival.
PMID- 23154718
TI - Chronic diarrhea as the presenting complaint of systemic lupus erythematosus in a
man.
AB - Systemic lupus can involve any part of the gastrointestinal (GI) tract. Diarrhea
generally results from complications arising from infection, drugs or
pancreatitis. We herein report the case of a 40-year-old hypertensive man with a
psychotic disorder in whom the evaluation of chronic diarrhea revealed a
diagnosis of systemic lupus erythematosus (SLE), diffuse proliferative
glomerulonephritis and protein-losing enteropathy that required treatment with
both steroids and mycophenolate mofetil. Over the following year, the patient
developed atrial fibrillation, miliary tuberculosis and generalized clonic tonic
seizures. He is currently under regular follow-up care and receives
antiepileptics, antihypertensives, diltiazem, amiodarone and warfarin.
PMID- 23154719
TI - Ulcerative colitis associated with isolated unilateral hypoglossal nerve palsy.
AB - We herein describe a rare case of ulcerative colitis associated with unilateral
hypoglossal nerve palsy. A 64-year-old woman developed severe active ulcerative
colitis and was treated with prednisolone. The dose of oral prednisolone was
reduced to 7.5 mg/day, following which the patient noticed slight dysphagia and a
speech disturbance. She was diagnosed with unilateral hypoglossal nerve palsy,
which was thought to be caused by mononeuritis. She was treated with intravenous
methylprednisolone at a dose of 500 mg/day, which improved the neuropathy. When
the neuropathy occurred, the patient was in a mildly active stage of ulcerative
colitis. We concluded that the mononeuritis observed in the present case was
likely an extraintestinal manifestation of ulcerative colitis.
PMID- 23154720
TI - Giant-cell myocarditis complicated by heparin-induced thrombocytopenia.
AB - Giant-cell myocarditis is a fatal autoimmune disorder that is often associated
with other autoimmune diseases. We herein describe a case of giant-cell
myocarditis complicated by heparin-induced thrombocytopenia (HIT). A 71-year-old
woman was admitted to our hospital due to palpitations and ptosis.
Echocardiography revealed hypokinesis in the left basal ventricular walls. Heart
failure gradually developed, and the condition was complicated by HIT. The
patient died of cardiogenic and septic shock caused by agranulocytosis. An
autopsy showed giant-cell myocarditis. When severe left ventricular dysfunction
due to an unknown cause is complicated by HIT, potential diagnoses of giant-cell
and other types of autoimmune myocarditis should thus be investigated.
PMID- 23154721
TI - A puzzling case of phospho-soda-induced hypocalcemia in a patient with multiple
endocrine neoplasia type 1-associated primary hyperparathyroidism.
AB - Although rare, symptomatic hypocalcemia may develop after the administration of
phospho-soda. We herein present the case of a patient with phospho-soda-induced
hypocalcemia who was surprisingly diagnosed with multiple endocrine neoplasia
type 1 (MEN1) caused by a heterozygous mutation in the MEN1 gene
(c628_631delACAG), thus resulting in a frameshift mutation (210ThrfsX224). In
addition to being the first report of phospho-soda-induced hypocalcemia in a
patient with MEN1-associated primary hyperparathyroidism, our report highlights
the complex nature of calcium balance in the human body and helps clinicians to
appreciate how confounding factors might affect the presentation of endocrine
disorders.
PMID- 23154722
TI - Acquired hemophilia A associated with IgG4-related lung disease in a patient with
autoimmune pancreatitis.
AB - Immunoglobulin G4 (IgG4)-related lung diseases can occur in patients with
autoimmune pancreatitis (AIP). However, the causal relationship between AIP and
acquired hemophilia A (AH) is unknown. We herein report the first case of AH
associated with IgG4-related lung disease that developed in a patient with AIP. A
65-year-old asymptomatic man with a history of AIP and sclerosing cholangitis
diagnosed at the age of 57 was admitted to our hospital due to an abnormal
reticulonodular shadow on chest X-ray. An examination of lung biopsy specimens
revealed IgG4-positive plasma cell infiltration in the interstitium. The serum
IgG4 level was elevated. One year later, the patient developed a progressive
severe hematoma in the left femoral muscle. On admission, laboratory examinations
revealed severe anemia with a markedly prolonged activated partial prothrombin
time, a decreased level of factor VIII (FVIII) activity, and the existence of
anti-FVIII antibodies. These findings were consistent with a diagnosis of AH. No
relapse has been observed over the past 25 months, during which time,
corticosteroid therapy has been continuously administered.
PMID- 23154723
TI - Organizing pneumonia complicated by cyst and pneumothorax formation.
AB - We present a case of organizing pneumonia complicated by pneumothorax in
association with cyst formation that developed during corticosteroid treatment.
Although it has been reported that the check-valve mechanism is a plausible cause
of cyst and pneumothorax formation in patients with organizing pneumonia, the
details of the corresponding pathological changes that occur in air-trapping have
not been elucidated. A pathological examination of lung specimens obtained with
video-assisted thoracoscopic surgery suggested that granulation tissues plugging
the bronchiole lumens might be a potential cause of the check-valve mechanism in
this case. In this report, we also reviewed eight other cases of organizing
pneumonia with pneumothorax or cyst formation.
PMID- 23154724
TI - Fatal community-acquired primary Candida pneumonia in an alcoholic patient.
AB - A 54-year-old alcoholic woman developed fulminant community-acquired pneumonia.
Despite receiving intensive support measures, she died four days after admission.
An autopsy revealed bronchopneumonia with clusters of pseudohyphae and yeast-like
fungi, and Candida albicans was isolated from both tracheal aspiration specimens
obtained on admission and the postmortem lungs. The absence of vessel invasion or
any other organ involvement led to a diagnosis of primary Candida pneumonia
secondary to aspiration, rather than pulmonary seeding from systemic infection.
Candida species isolated from respiratory tract samples are usually regarded as
originating from colonization; however, the possibility for true Candida
pneumonia should be taken into account, even in the setting of community-acquired
pneumonia.
PMID- 23154725
TI - Eosinophilic lung disease complicated by Kimura's disease: a case report and
literature review.
AB - Kimura's disease (KD) or eosinophilic lymphogranuloma is a rare chronic
inflammatory disorder of unknown etiology that occurs primarily in Asians. A 51
year-old man diagnosed three years earlier with KD of a left neck nodule was
admitted to our hospital with a productive cough and pulmonary infiltration.
Bronchoscopy was performed, and a diagnosis of eosinophilic lung disease (ELD)
was made. The patient's condition improved after receiving corticosteroid
treatment. Complications such as nephrotic syndrome have been reported in
patients with KD; however, ELD has not been previously described. To the best of
our knowledge, this is the first report of ELD related to KD.
PMID- 23154726
TI - Divergence paralysis caused by acute midbrain infarction.
AB - A 41-year-old woman with idiopathic thrombocytopenic purpura and dyslipidemia
abruptly developed vertigo, truncal ataxia and divergence paralysis. Cranial
magnetic resonance imaging demonstrated the presence of infarction in the left
superior paramedian mesencephalic artery involving the vicinity of the
periaqueductal gray matter. The symptoms rapidly resolved under the
administration of anti-platelet agents. The precise location of the hypothetical
divergence center of the ocular motor system remains unclear because the lesions
responsible for divergence paralysis are rarely identified on neuroimaging. We
emphasize that this is a first reported case of DP caused by acute midbrain
infarction and speculate that the mesencephalic reticular formation may be
partially involved.
PMID- 23154727
TI - Recurrent anterior uveitis with hypopyon revealing relapsing polychondritis.
AB - Relapsing polychondritis (RP) is a rare disease involving cartilaginous
structures, predominantly the ears, nose and laryngotracheobronchial tree. The
eyes, cardiovascular system, peripheral joints, skin, and central nervous system
may also be affected. Involvement of all ocular structures has been described.
Non-granulomatous uveitis is a common feature; however hypopyon is uncommon. We
herein present the case of a 42-year-old man who had been diagnosed with
bronchial asthma for a long period; and who presented with recurrent hypopyon
uveitis as a revealing manifestation of relapsing polychondritis. We emphasize
that RP should therefore be considered in the differential diagnosis of sterile
hypopyon uveitis.
PMID- 23154728
TI - ANCA-associated vasculitis with central retinal artery occlusion developing
during treatment with methimazole.
AB - A 63-year-old woman suddenly developed central retinal artery occlusion following
a slight fever while being treated with methimazole (MMI) for hyperthyroidism.
She was diagnosed to have anti-neutrophil cytoplasmic antibody (ANCA)-associated
vasculitis (AAV) based on increased inflammatory reactions with positive
myeloperoxidase-ANCA in the serum. Her visual acuity remained low despite
immediate treatment with corticosteroids and cyclophosphamide after cessation of
MMI, which may have played a role in the pathogenesis of AAV. Central retinal
artery occlusion is a rare manifestation of AAV; however, it is important with
regard to the possibility of serious sequelae.
PMID- 23154729
TI - Foot ulcers caused by rheumatoid vasculitis in a patient with rheumatoid
arthritis undergoing etanercept treatment.
AB - A 59-year-old woman with a 10-year history of rheumatoid arthritis (RA) presented
with chronic ulcers on both feet while undergoing treatment with etanercept.
Rheumatoid vasculitis (RV) was diagnosed, and the patient was treated with
immunosuppressant drugs and skin grafting. Although anti-tumor necrosis factor
(TNF) agents are known to induce vasculitis, vasculitis can also be caused by
active RA. Accordingly, the cause of vasculitis in RA patients receiving anti-TNF
therapy must be evaluated carefully.
PMID- 23154730
TI - Recurrent Helicobacter cinaedi cellulitis and bacteremia in a patient with
systemic lupus erythematosus.
AB - A 31-year-old woman who had developed systemic lupus erythematosus at 17 years of
age was admitted to the hospital for suspected cellulitis in the lower
extremities. A blood culture performed upon admission to the hospital detected
Helicobacter cinaedi (H. cinaedi), which was also isolated in blood and fecal
cultures obtained on the 42nd hospital day. Bacterial translocation of H. cinaedi
present in the intestines may have led to the development of recurrent bacteremia
and cellulitis. In cases such as this, appropriate antibiotics therapy might be
needed for more than one month. Moreover, H. cinaedi, a cause of emerging
infections, requires a long period of time to grow; therefore it is important to
extend the culture duration when the presence of this bacterium is suspected.
PMID- 23154732
TI - Raoultella ornithinolytica bacteremia in cancer patients: report of three cases.
AB - Raoultella ornithinolytica is a Gram-negative aerobic bacillus reclassified in
the new genus from the Klebsiella species based on new genetic approaches;
however, human infections caused by R. ornithinolytica are rare. We herein report
three cases of R. ornithinolytica bacteremia associated with biliary tract
infections in cancer patients. R. ornithinolytica can be a causative pathogen of
biliary tract infection in cancer patients.
PMID- 23154731
TI - Spondylodiscitis complicated by an epidural abscess and meningitis caused by
Bacteroides fragilis.
AB - Bacteroides fragilis is a rare causative agent of spondylodiscitis. The
pathophysiology of B. fragilis in spondylodiscitis remains largely unclear
because of its rare occurrence. We herein report a case of spondylodiscitis
complicated by an epidural abscess and meningitis; B. fragilis was detected in
the blood of the patient. Moreover, the patient had a splenic abscess that was
confirmed on magnetic resonance imaging. The patient completely recovered with
antimicrobial therapy alone.
PMID- 23154733
TI - Sudden cardiac arrest caused by tuberculous pericarditis with hemorrhagic
pericardial effusion.
AB - As tuberculosis still exists in Japan, tuberculous pericarditis is a major health
issue. Tuberculous pericarditis is difficult to diagnose and leads to poor
outcomes when left untreated. We herein report the case of a patient who was
admitted to the hospital after undergoing resuscitation for cardiopulmonary
arrest. Mycobacterium tuberculosis was detected in his hemorrhagic pericardial
fluid and tuberculous pericarditis was diagnosed. The administration of
antituberculous medication resulted in marked improvements. A diagnosis of
tuberculous pericarditis, in addition to other causes such as malignant tumors,
should therefore be considered in the differential diagnosis for cases presenting
with hemorrhagic pericardial effusion, even in those involving sudden cardiac
arrest.
PMID- 23154734
TI - Tuberculous cellulitis in a patient with chronic kidney disease and polymyalgia
rheumatica.
AB - An 89-year-old man with advanced renal failure, polymyalgia rheumatica and a past
history of tuberculosis was admitted with a high fever. Erythema and swelling
appeared in the femoral region. Since the cellulitis failed to respond to
antibiotic therapy, a skin biopsy was performed. The specimen showed the presence
of epithelioid cell granuloma and panniculitis. Acid-fast organisms were found on
Ziehl-Neelsen staining. A polymerase chain reaction test of tuberculosis was
positive. Although a diagnosis of miliary tuberculosis was suggested,
examinations of a bone marrow biopsy and fundoscopy revealed normal results. The
patient's symptoms improved following treatment with isoniazid, rifampicin and
ethambutol. This case represents an unusual presentation of tuberculous
cellulitis in an immunocompromised patient.
PMID- 23154735
TI - Severe Legionnaires' disease with pneumonia and biopsy-confirmed myocarditis most
likely caused by Legionella pneumophila serogroup 6.
AB - We herein describe the successful treatment of a patient with possible Legionella
pneumophila serogroup 6 infection complicated by pneumonia and myocarditis. A 32
year-old man presented with a five-day history of cough, dyspnea and chest pain.
Chest radiography revealed patchy opacities in both lungs suggestive of bilateral
pneumonia, and a urinary antigen test for Legionella pneumophila was positive.
After admission, the patient developed congestive heart failure due to
pathologically confirmed myocarditis. He was successfully treated with
minocycline, macrolide, steroids and noninvasive positive-pressure ventilation
(NPPV). He eventually recovered with a normalized cardiac function. L.
pneumophila serogroup 6 was isolated from the bathwater in the patient's home.
PMID- 23154736
TI - Elevated coagulation factor VIII plasma activity in a patient with
lymphangiosarcoma.
AB - A 72-year-old woman was referred to our hospital for palliative care. Fifteen
years earlier, she had undergone total hysterectomy and radiotherapy for cervical
cancer. One year before her referral, she visited a hospital due to a gait
disturbance and was diagnosed with lymphangiosarcoma. The level of coagulation
factor VIII plasma activity was >201% (normal range: 62-145%) and the
immunohistochemical results were positive for factor VIII-related antigen in a
tumor specimen. To the best of our knowledge, this is the first report of high
coagulation factor VIII plasma activity in a patient with lymphangiosarcoma.
PMID- 23154737
TI - A giant amebic liver abscess.
PMID- 23154738
TI - Polysplenia in an adult patient.
PMID- 23154739
TI - Kawasaki disease with a giant coronary aneurysm.
PMID- 23154740
TI - Massive thyroid hematoma developing after a fine-needle aspiration biopsy.
PMID- 23154741
TI - Low bone mass in Ehlers-Danlos syndrome.
PMID- 23154742
TI - Churg-Strauss syndrome with endobronchial eosinophilic vasculitis.
PMID- 23154743
TI - Downgaze-limited diplopia caused by midbrain infarction.
PMID- 23154744
TI - Chest wall tuberculosis.
PMID- 23154745
TI - Green plasma and pregnancy.
PMID- 23154746
TI - How much do focal infarcts distort white matter lesions and global cerebral
atrophy measures?.
AB - BACKGROUND: White matter lesions (WML) and brain atrophy are important biomarkers
in stroke and dementia. Stroke lesions, either acute or old, symptomatic or
silent, are common in older people. Such stroke lesions can have similar signals
to WML and cerebrospinal fluid (CSF) on magnetic resonance (MR) images, and may
be classified accidentally as WML or CSF by MR image processing algorithms,
distorting WML and brain atrophy volume from the true volume. We evaluated the
effect that acute or old stroke lesions at baseline, and new stroke lesions
occurring during follow-up, could have on measurement of WML volume, cerebral
atrophy and their longitudinal progression. METHODS: We used MR imaging data from
patients who had originally presented with acute lacunar or minor cortical
ischaemic stroke symptoms, recruited prospectively, who were scanned at baseline
and about 3 years later. We measured WML and CSF volumes (ml) semi-automatically.
We manually outlined the acute index stroke lesion (ISL), any old stroke lesions
present at baseline, and new lesions appearing de novo during follow-up. We
compared baseline and follow-up WML volume, cerebral atrophy and their
longitudinal progression excluding and including the acute ISL, old and de novo
stroke lesions. A non-parametric test (Wilcoxon's signed rank test) was used to
compare the effects. RESULTS: Among 46 patients (mean age 72 years), 33 had an
ISL visible on MR imaging (median volume 2.05 ml, IQR 0.88-8.88) and 7 of the 33
had old lacunes at baseline: WML volume was 8.54 ml (IQR 5.86-15.80) excluding
versus 10.98 ml (IQR 6.91-24.86) including ISL (p < 0.001). At follow-up, median
39 months later (IQR 30-45), 3 patients had a de novo stroke lesion; total stroke
lesion volume had decreased in 11 and increased in 22 patients: WML volume was
12.17 ml (IQR 8.54-19.86) excluding versus 14.79 ml (IQR 10.02-38.03) including
total stroke lesions (p < 0.001). Including/excluding lacunes at baseline or
follow-up also made small differences. Twenty-two of the 33 patients had tissue
loss due to stroke lesions between baseline and follow-up, resulting in a net
median brain tissue volume loss (i.e. atrophy) during follow-up of 24.49 ml (IQR
12.87-54.01) excluding versus 24.61 ml (IQR 15.54-54.04) including tissue loss
due to stroke lesions (p < 0.001). Including stroke lesions in the WML volume
added substantial noise, reduced statistical power, and thus increased sample
size estimated for a clinical trial. CONCLUSIONS: Failure to exclude even small
stroke lesions distorts WML volume, cerebral atrophy and their longitudinal
progression measurements. This has important implications for design and sample
size calculations for observational studies and randomised trials using WML
volume, WML progression or brain atrophy as outcome measures. Improved methods of
discriminating between stroke lesions and WML, and between tissue loss due to
stroke lesions and true brain atrophy are required.
PMID- 23154749
TI - Computational Hammett analysis of redox based oxy-insertion by Pt(II) complexes.
AB - A computational Hammett analysis of oxy-insertion into platinum-aryl bonds is
performed. Modeled transformations involve the two-step conversion of
[((X)bpy)Pt(R)(OY)](+) (R = p- or m-X-C(6)H(4); Y = 4- or 3-X-pyridine; (X)bpy =
4,4'- or 5,5'-X-bpy; X = NO(2), H, OMe, NMe(2)) proceeding through a Pt-oxo
intermediate to form aryloxide [((X)bpy)Pt(OR)(Y)](+), which contrasts a one-step
non-redox (Baeyer-Villiger) oxy-insertion. A structural connection is proposed
between redox and non-redox transition states, linked to, among other parameters,
oxidant identity. The electronic impact of the catalytic components is compared
to previous Hammett studies on OMBV transformations. The Hammett sensitivity for
aryl migration is diminished for the migrating group (R) and leaving group (Y),
components as compared to OMBV transitions, while the bipyridine supporting
ligand (L(n)) has an increased impact. The Hammett impact of R, Y and L(n) upon
the aryl migration transition state is small in a global sense, ca. 5 kcal mol(
1); therefore, we conclude that the metal and oxidant are the most important
factors in controlling oxy-insertion kinetics for these late metal systems. These
results also point to a possible mechanistic advantage for redox over non-redox
functionalization of hydrocarbons to alcohols.
PMID- 23154748
TI - Aggressive B-cell lymphomas: how many categories do we need?
AB - Aggressive B-cell lymphomas are diverse group of neoplasms that arise at
different stages of B-cell development and by various mechanisms of neoplastic
transformation. The aggressive B-cell lymphomas include many types, subtypes and
variants of diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), mantle
cell lymphoma and its blastoid variant, and B lymphoblastic lymphoma. Differences
in histology, cytogenetic and molecular abnormalities, as well as the
relationship with the tumor microenvironment, help define characteristic
signatures for these neoplasms, and in turn dictate potential therapeutic
targets. Rather than survey the entire spectrum of aggressive B-cell lymphomas,
this report aims to identify and characterize important clinically aggressive
subtypes of DLBCL, and explore the relationship of DLBCL to BL and the gray zone
between them (B-cell lymphoma unclassifiable with features intermediate between
DLBCL and BL).
PMID- 23154750
TI - Investigating the robustness of ion beam therapy treatment plans to uncertainties
in biological treatment parameters.
AB - Uncertainties in determining clinically used relative biological effectiveness
(RBE) values for ion beam therapy carry the risk of absolute and relative
misestimations of RBE-weighted doses for clinical scenarios. This study assesses
the consequences of hypothetical misestimations of input parameters to the RBE
modelling for carbon ion treatment plans by a variational approach. The impact of
the variations on resulting cell survival and RBE values is evaluated as a
function of the remaining ion range. In addition, the sensitivity to
misestimations in RBE modelling is compared for single fields and two opposed
fields using differing optimization criteria. It is demonstrated for single
treatment fields that moderate variations (up to +/-50%) of representative
nominal input parameters for four tumours result mainly in a misestimation of the
RBE-weighted dose in the planning target volume (PTV) by a constant factor and
only smaller RBE-weighted dose gradients. Ensuring a more uniform radiation
quality in the PTV eases the clinical importance of uncertainties in the
radiobiological treatment parameters, as for such a condition uncertainties tend
to result only in a systematic misestimation of RBE-weighted dose in the PTV by a
constant factor. Two opposed carbon ion fields with a constant RBE in the PTV are
found to result in rather robust conditions. Treatments using two ion species may
be used to achieve a constant RBE in the PTV irrespective of the size and depth
of the spread-out Bragg peak.
PMID- 23154751
TI - Variation of tibial plateau geometry and cruciate ligament coordinates in six
breeds of dogs.
AB - OBJECTIVES: The first aim of this study was to examine whether or not variations
concerning the conformational characteristics of the proximal surface of the
tibial plateau exist among six different dog breeds as well as within the same
breed. The second aim of this study was to determine the coordinates of the
cruciate ligaments. METHODS: One hundred and four tibias of 52 mature dogs from
six different breeds were used. Photographs of the proximal surface of tibial
plateau were taken, and measurements for the length, width and area of the tibial
plateau, and the lateral and medial condyles were taken. In addition, the
intercondylar width, height of Gerdy's tubercle, popliteal notch depth, and
extensor groove depth were measured and recorded. The quotients from these
measurements were calculated and compared amongst the dog breeds. The coordinates
of the cruciate ligaments, according to the centre of tibial plateau, were also
determined. RESULTS: Based on the calculated quotients, variations in the
geometry of the tibial plateau geometry were common among the breeds. Within the
same breed, on the other hand, length and width measurements of the tibial
plateau were the least variable parameters among the other parameters examined.
The cranial cruciate ligament was located in front of the surface centre of
tibial plateau in all breeds. The position of cranial cruciate ligament was more
variable in the craniocaudal direction than that observed in the mediolateral
direction; this was the exact opposite of caudal cruciate ligament. CLINICAL
SIGNIFICANCE: The inter-breed variations of the quotients determined in the
present study may facilitate attempts aimed to assess the risk factors of stifle
joint injury and to design total knee prostheses.
PMID- 23154752
TI - Fluorescence enhancement from nano-gap embedded plasmonic gratings by a novel
fabrication technique with HD-DVD.
AB - We demonstrate strong electromagnetic field enhancement from nano-gaps embedded
in silver gratings for visible wavelengths. These structures fabricated using a
store-bought HD-DVD worth $10 and conventional micro-contact printing techniques
have shown maximum fluorescence enhancement factors of up to 118 times when
compared to a glass substrate under epi-fluorescent conditions. The novel
fabrication procedure provides for the development of a cost-effective and facile
plasmonic substrate for low-level chemical and biological detection.
Electromagnetic field simulations were also performed that reveal the strong
field confinement in the nano-gap region embedded in the silver grating, which is
attributed to the combined effect of localized as well as propagating surface
plasmons.
PMID- 23154753
TI - Plaque characteristics of asymptomatic carotid stenosis and risk of stroke.
AB - BACKGROUND: The optimal treatment of asymptomatic carotid stenosis (ACS) is
controversial. To optimize the risk-benefit ratio of carotid artery
revascularization, it is crucial to identify ACS patients who are at increased
stroke risk. Recent data suggest that plaque vulnerability depends on its
composition. Therefore, we assessed plaque composition in ACS to determine
predictors for ipsilateral cerebrovascular events. METHODS: 62 patients with 65
ACS >=50% underwent 3-T MRI of the carotid bifurcation (TOF, special dark-blood
weighted noncontrast and contrast-enhanced T(1) and T(2) images) and of the
brain. The different plaque components (lipid core, intraplaque hemorrhage,
calcification and the status of the fibrous cap) were assessed. Furthermore, the
plaque volume and the volume of clinically silent cortical and subcortical
infarcts in the territory of the stenosed carotid artery as seen on FLAIR images
were determined by using a semi-automated software. Carotid stenosis was
considered asymptomatic if there had not been any clinically apparent ischemic
events in the corresponding vascular territory within the previous 6 months.
During follow-up, information on the occurrence of cerebrovascular events,
medical treatment and sonographic changes of the stenosis was collected. RESULTS:
At baseline, 24 ACS (37%) were classified as high grade. A lipid-rich necrotic
core was the dominant plaque component in 16 ACS (25%). The plaque volume was
higher in ACS with a lipid-rich necrotic core as dominant plaque component (p =
0.002) and in patients with prior stroke/TIA (p = 0.010). After a median follow
up of 18.9 months (interquartile range 3.5-30.1) there were 2 ipsilateral strokes
and 3 ipsilateral TIAs. The average annual event rate was 7.7%. A lipid-rich
necrotic core (HR 7.21; 95% CI 1.12-46.28; p = 0.037), sonographic progression of
the stenosis (HR 7.00; 95% CI 1.13-41.34; p = 0.036), history of stroke (HR
11.03; 95% CI 1.23-99.36; p = 0.032), and the volume of clinically asymptomatic
ischemic brain lesions (HR 1.14/cm(3); 95% CI 1.03-1.25; p = 0.008) predicted
cerebrovascular events. Patients on statin therapy at follow-up were at lower
risk of events (HR 0.17; 95% CI 0.03-1.00; p = 0.05). CONCLUSIONS: In addition to
medical history and sonographic findings, a lipid-rich necrotic core within the
plaque turned out as a predictor of cerebrovascular events. Therefore, MR imaging
of carotid plaques deserves further attention and might be helpful to improve
risk stratification of asymptomatic carotid disease. The identified predictors
could be combined in a risk model and tested in larger prospective studies.
PMID- 23154754
TI - Two thermoformable spiral metallic ureteral stents in a patient with ileal
conduit and distal stenosis of the ureters.
AB - The insertion of two thermoformable ureteral titanium spiral stents (Memokath(r)
051) through ileal conduit due to bilateral ureteral stenosis distally has not
been described in the English literature so far. We present the case of a young
female patient with a history of ileal conduit urinary diversion due to
congenital urinary bladder exstrophy, who had multiple previous surgeries and the
insertion of two Memokath(r) ureteral stents in both ureters due to distal
ureteral stenosis.
PMID- 23154755
TI - An international survey of deep brain stimulation procedural steps.
AB - BACKGROUND: Deep brain stimulation (DBS) surgery is standard of care for the
treatment of certain movement disorders. OBJECTIVE: We sought to characterize the
spectrum of steps performed in DBS surgery, at centers around the world where
this surgery is performed. METHODS: We identified the main steps in DBS surgery
workflow and grouped these 19 steps into 3 phases (preoperative, operative, and
postoperative). A survey tool, informed by a pilot survey, was administered
internationally by trained study personnel at high- and low-volume DBS centers.
Procedural components, duration, and surgeon motivational factors were assessed.
Cluster analysis was used to identify procedural and behavioral clusters.
RESULTS: One hundred eighty-five procedure workflow surveys (143 DBS centers) and
65 online surveys of surgeon motivational drivers were completed (45% response
rate). Significant heterogeneity in technique, operative time, and surgeon
motivational drivers was reported across centers. CONCLUSIONS: We provide a
description of the procedural steps involved in DBS surgery and the duration of
these steps, based on an international survey. These data will enable individual
surgeons and centers to examine their own experience relative to colleagues at
other centers and in other countries. Such information could also be useful in
comparing efficiencies and identifying workflow obstacles between different
hospital environments.
PMID- 23154756
TI - Increased arterial stiffness and extracellular matrix reorganization in
intrauterine growth-restricted fetal sheep.
AB - BACKGROUND: Fetal intrauterine growth restriction (IUGR) results in increased
placental resistance to blood flow, fetal hypertension, and increased pulsatility
stresses shown to lead to vascular remodeling. We tested our hypothesis that IUGR
causes decreased compliance in the carotid and umbilical arteries due to altered
extracellular matrix (ECM) composition and structure. METHODS: A sheep model of
placental insufficiency-induced IUGR (PI-IUGR) was created by exposure of the
pregnant ewe to elevated ambient temperatures. Umbilical and carotid arteries
from near-term fetuses were tested with pressure-diameter measurements to compare
passive compliance in control and PI-IUGR tissues. ECM composition was measured
via biochemical assay, and the organization was determined by using histology and
second-harmonic generation imaging. RESULTS: We found that PI-IUGR increased
arterial stiffness with increased collagen engagement, or transition stretch. PI
IUGR carotid arteries exhibited increased collagen and elastin quantity, and PI
IUGR umbilical arteries exhibited increased sulfated glycosaminoglycans.
Histomorphology showed altered collagen-to-elastin ratios with altered cellular
proliferation. Increased stiffness indicates altered collagen-to-elastin ratios
with less elastin contribution leading to increased collagen engagement.
CONCLUSION: Because vessel stiffness is a significant predictor in the
development of hypertension, disrupted ECM deposition in IUGR provides a
potential link between IUGR and adult hypertension.
PMID- 23154757
TI - Noninvasive measurement of intestinal epithelial damage at time of refeeding can
predict clinical outcome after necrotizing enterocolitis.
AB - BACKGROUND: Reintroduction of enteral nutrition in neonates with necrotizing
enterocolitis (NEC) should take place when the gut is ready for its normal
function. Too early a start of oral feeding might lead to disease relapse,
whereas prolonged discontinuation of enteral nutrition is associated with
impaired gut function and parenteral nutrition-related complications. This study
evaluated whether noninvasive urinary measurement of intestinal fatty acid
binding protein (I-FABP) at the time of refeeding can predict clinical outcome in
neonates with NEC. METHODS: Urinary I-FABP concentrations were measured in 21
infants with NEC just before reintroducing enteral nutrition. Poor outcome was
defined as unsuccessful reintroduction of enteral feeding (EF), (re)operation for
NEC, or death related to NEC after reintroduction of EF. RESULTS: Median urinary
I-FABP levels in neonates with poor outcome (n = 5) were significantly higher as
compared with I-FABP levels in neonates with good outcome (n = 16) (P < 0.01). A
clinically significant cutoff value of 963 pg/ml was found to discriminate
between infants with poor outcome and those with good outcome (sensitivity 80%,
specificity 94%). CONCLUSION: Noninvasive urinary I-FABP measurement at time of
refeeding differentiates neonates with poor outcome from neonates with good
outcome in NEC. Urinary I-FABP measurement may therefore be helpful in the timing
of EF in neonates with NEC.
PMID- 23154758
TI - Development of methods to distinguish between durum/common wheat and common wheat
in blended flour using PCR.
AB - A PCR-based method was developed to distinguish between durum/common wheat and
common wheat by leveraging slight differences of DNA sequence in Starch Synthase
II (SS II) coded on wheat A, B and D genomes. A primer pair, SS II ex7-U/L, was
designed to hybridize with a conserved DNA sequence region found in SS II-A, B
and D genes. Another primer pair, SS II-D 1769U/1889L, was constructed to
recognize a unique sequence in the SS II-D gene. The target region of SS II ex7
U/L with the size of 114 bp was amplified from durum and common wheat DNA, while
no amplification was observed from any cereals other than those in the wheat
genus. A DNA fragment with the size of 121 bp was specifically amplified from
common wheat with SS II-D 1769U/1889L. In blended flour prepared from wheat and
other cereals, the developed PCR system composed of two primer pairs effectively
detected durum/common wheat and common wheat. These results suggested that PCR
using two primer pairs is useful for detecting common and/or durum wheat in
blended flour and could be utilized to ensure accurate food labeling.
PMID- 23154759
TI - An endogenous reference gene of common and durum wheat for detection of
genetically modified wheat.
AB - To develop a method for detecting GM wheat that may be marketed in the near
future, we evaluated the proline-rich protein (PRP) gene as an endogenous
reference gene of common wheat (Triticum aestivum L.) and durum wheat (Triticum
durum L.). Real-time PCR analysis showed that only DNA of wheat was amplified and
no amplification product was observed for phylogenetically related cereals,
indicating that the PRP detection system is specific to wheat. The intensities of
the amplification products and Ct values among all wheat samples used in this
study were very similar, with no nonspecific or additional amplification,
indicating that the PRP detection system has high sequence stability. The limit
of detection was estimated at 5 haploid genome copies. The PRP region was
demonstrated to be present as a single or double copy in the common wheat haploid
genome. Furthermore, the PRP detection system showed a highly linear relationship
between Ct values and the amount of plasmid DNA, indicating that an appropriate
calibration curve could be constructed for quantitative detection of GM wheat.
All these results indicate that the PRP gene is a suitable endogenous reference
gene for PCR-based detection of GM wheat.
PMID- 23154760
TI - Aflatoxins B and g contamination and aflatoxigenic fungi in nutmeg.
AB - This study examined the distribution of aflatoxigenic fungi in 25 imported
Indonesian nutmeg samples contaminated with aflatoxins Bs or Bs and Gs. The
incidence of aflatoxigenic fungi in the samples contaminated with high levels of
aflatoxin was significantly higher than that in the samples with low levels of
the toxins(r=0.752). The aflatoxin production of isolates from the samples in
cultures of YES broth was examined by means of TLC and HPLC analyses. The ability
of isolates to produce aflatoxins did not necessarily correlate with the
contamination levels of aflatoxin in the samples. We isolated aflatoxins B and G
producing fungi from 3 samples contaminated with the high levels of aflatoxins B
and G. The aflatoxigenic isolates were identified as Aspergillus nomius and A.
bombycis based on morphological characters, growth rates at 37 degrees C and 42
degrees C and also molecular-genetic methods. Our results indicate that these two
species are mainly responsible for aflatoxin G contamination in nutmeg products.
PMID- 23154761
TI - Determination method of clomeprop and clomeprop acid in livestock and seafood
products by LC-MS/MS.
AB - A method using liquid chromatography with tandem mass spectrometry has been
developed for the determination of clomeprop and its metabolite clomeprop acid in
livestock and seafood products. Clomeprop and clomeprop acid were extracted with
acetone-n-hexane mixture under acidic conditions, and were defatted by liquid
liquid separation using acetonitrile and n-hexane, followed cleanup with SAX and
PSA cartridges. The average recoveries from 10 kinds of food (bovine muscle,
bovine fat, bovine liver, milk, yellowtail, salmon, eel, fresh water clam, egg
and honey) spiked at the level of the MRLs or at uniform limits (0.01 ppm) were
in the range of 81-97% for clomeprop and 93-101% for clomeprop acid.
Repeatability was in the range of 2.1-14% for clomeprop and 1.3-4.0% for
clomeprop acid. The quantitation limits were 0.002 mg/kg for clomeprop and
0.00154 mg/kg (0.002 mg/kg as clomeprop) for clomeprop acid.
PMID- 23154762
TI - Investigation of whether CLSI broth microdilution method is applicable for MICs
Determination of Enterococcus species.
AB - The broth microdilution (BMD) method is an antimicrobial susceptibility testing
method defined as a guideline by the Clinical and Laboratory Standards Institute
(CLSI). To date, the Japanese Veterinary Antimicrobial Resistance Monitoring
System (JVARM), has adopted the agar dilution (AD) method for monitoring
antimicrobial resistances targeting isolates of Enterococcus spp., found in the
fecal flora of food-producing animals, as indicator bacteria. However, the AD
method is tedious, and time-consuming. In order to examine whether it could be
replaced with the BMD method, the two methods were compared in terms of the
correlation of MICs. In this study, the BMD results agreed with the AD results
within +/-1 log(2) dilutions in 72.3% of cases, except for the antimicrobial feed
additive, Nosiheptide (NHT). Similarly, except for NHT, the MIC(50) and MIC(90)
values obtained by the two methods were well correlated. In conclusion, our
results indicate that the BMD method might be suitable for antimicrobial
susceptibility testing targeting Enterococcus spp..
PMID- 23154763
TI - Behavior of pesticides in coffee beans during the roasting process.
AB - In Japan, maximum residue limits for pesticides (MRL) in coffee are set on green
coffee beans, but not roasted coffee beans, although roasted beans are actually
used to prepare coffee for drinking. Little is known about the behavior of
pesticides during the roasting process. In the present study, we examined the
changes in the concentration of pesticide (organochlorine: gamma-BHC, chlordane
and heptachlor) residues in coffee beans during the roasting process. We prepared
green coffee beans spiked with these pesticides (0.2 and 1.0 MUg/g), and the
residue levels in the beans were measured before and after the roasting process.
We determined the residual rate after the roasting process. gamma-BHC was not
detectable at all, and more than 90% of chlordane was lost after the roasting
(3.1 and 5.1% of chlordane remained in the beans spiked with 0.2 and 1.0 MUg/g of
chlordane, respectively). A low level of heptachlor (0.72%) was left in the
coffee beans spiked with 1 MUg/g of heptachlor. Disappearance of gamma-BHC during
the roasting process may be due to the high vapor pressure of gamma-BHC, while
chlordane has a lower vapor pressure. We also examined the behavior of piperonyl
butoxide and atrazine during the roasting process. Piperonyl butoxide behaved
similarly to chlordane, but atrazine disappeared after the roasting process,
because it is unstable to heat.
PMID- 23154764
TI - Discrimination of mushrooms causing food-poisoning incidents by using DNA
sequence analysis.
AB - In this study, the identification of mushrooms by using DNA analysis was
investigated. Our analysis of internal transcribed spacer (ITS) regions revealed
that a DNA-based method could be applicable for samples that are difficult to
distinguish in terms of the morphological characteristics. PCR amplification
using templates extracted from cooked samples gave sufficient fragments to
analyze the sequence. However, treatment with simulated gastric fluid (SGF) for
more than 30 min affected the analysis of the ITS region. Application to samples
of vomit is also discussed.
PMID- 23154766
TI - Ki67 labeling index in neuroendocrine tumors of the gastrointestinal and
pancreatobiliary tract: to count or not to count is not the question, but rather
how to count.
PMID- 23154765
TI - Development and validation of rapid analysis method for multi-class veterinary
drugs in livestock products by LC-MS/MS.
AB - A method for rapid analysis of multi-class residual veterinary drugs in livestock
products was developed and validated in accordance with the Japanese guideline
for pesticides. Using LC-MS/MS, 43 multi-class veterinary drugs, including
sulfonamides, quinolones, coccidiostats and antiparasites, could be analyzed
simultaneously in only 18 minutes. The extraction process was developed by
modifying the QuEChERS approach to provide faster and less expensive extraction.
The samples were extracted by using two kinds of solvent, acetonitrile and
acetonitrile including 1 vol% formic acid, and salted out with magnesium sulfate,
trisodium citrate and sodium chloride. Using these two extractants, 40 out of 43
drugs satisfied the guideline criteria in bovine muscle and swine muscle, 39
drugs were found in chicken muscle, and 37 drugs were found in eggs. The limit of
quantification was less than the MRL for all analytes.
PMID- 23154767
TI - Clinicopathologic analysis of matched primary and recurrent endometrial
carcinoma.
AB - It is unknown whether the type and grade of a primary endometrial carcinoma is
reliably maintained in recurrence. All matched primary and recurrent endometrial
carcinomas diagnosed from 2000 to 2010 at our institution were identified; 34
cases had available slides. Histologic classification was performed using
modifications to the World Health Organization criteria. Immunohistochemical
analysis for p53, p16, progesterone receptor (PR), and DNA mismatch-repair
proteins (MMR) (MLH1, MSH2, MSH6, and PMS2) was performed. Endometrioid carcinoma
recurrences were mostly local, whereas serous carcinoma recurrences were mostly
peritoneal. Compared with endometrioid carcinoma patients, serous carcinoma
patients were older, presented at high stage, and had shorter survival. Serous
carcinomas were the most common recurrent endometrial carcinoma (18/34 cases).
Overall, 21 cases (62%) displayed similar morphology when comparing primary and
recurrent carcinomas, whereas 13 displayed discordant morphology. Seven of 13
endometrioid carcinomas (54%) had a morphologically discordant recurrence,
compared with 3 of 14 serous carcinomas (21%), 1 of 4 morphologically ambiguous
carcinomas (25%), and both mixed epithelial carcinomas. Serous and
morphologically ambiguous carcinomas therefore demonstrated relative morphologic
fidelity compared with endometrioid carcinomas. Four morphologically discordant
cases demonstrated either pure clear cell carcinoma or clear cell features at
recurrence. Seven of 23 matched pairs displayed discordant PR results, with 5
cases, including both endometrioid and serous carcinomas, showing diminished PR
expression at recurrence. p53, p16, and DNA MMR staining results were generally
concordant when evaluating matched pairs, with only occasional exceptions. Sixty
four percent of all pure endometrioid carcinomas and mixed epithelial carcinomas
with an endometrioid component showed loss of expression of MLH1 and/or PMS2; no
serous carcinoma demonstrated this abnormality. Clinical and immunohistochemical
data supported the use of modifications to the World Health Organization
diagnostic criteria. More importantly, the data suggest that when confronted with
recurrent endometrial carcinoma, particularly a serous carcinoma, it is
reasonable to base therapeutic decisions on the type of the primary tumor,
especially if sampling or excising the recurrent tumor is problematic. However,
in light of the PR results, sampling a recurrent endometrioid carcinoma may be
worthwhile if hormonal therapy is planned. Recurrent endometrioid carcinoma may
be enriched for tumors with DNA MMR abnormalities.
PMID- 23154768
TI - Silver-enhanced in situ hybridization for determination of EGFR copy number
alterations in non-small cell lung cancer.
AB - Epidermal growth factor receptor (EGFR) gene mutation and high gene copy number
(CN) predict response to EGFR tyrosine kinase inhibitor therapy in the
adenocarcinoma subtype of non-small cell lung cancer (NSCLC). The aims of this
study were first to compare automated enzyme metallographic silver-enhanced in
situ hybridization (SISH) with conventionally used fluorescence in situ
hybridization (FISH) in the determination of EGFR CN in NSCLC tissue sections,
and second to assess the association of EGFR CN with EGFR mutations and
clinicopathological parameters. FISH and SISH were performed on tissue
microarrays and large sections. Samples from 56 consecutively surgically resected
NSCLC patients (cohort 1) and from 60 selected lung adenocarcinoma patients
(cohort 2) were analyzed. EGFR CN was classified applying the Colorado criteria,
and agreement between both methods was evaluated using kappa values. EGFR CN was
compared with EGFR protein expression and EGFR gene mutations. The results of
SISH and FISH were identical in 114 of the 116 cases examined using the 2
techniques. One case was FISH+, SISH-, and 1 case was FISH- and SISH+. The
agreement between the 2 methods was good in cohort 1 (kappa=0.642 [0.428, 0.823])
and excellent in cohort 2 (kappa=0.963 [0.870, 1.000]). EGFR positivity by FISH
and SISH was associated with high EGFR protein expression (P<0.001) and EGFR
mutation (P<0.001). These results validate the use of SISH for assessing EGFR CN
alterations in NSCLC. The advantage of a permanent result and the possibility of
bright-field microscopy make SISH an attractive alternative to FISH.
PMID- 23154769
TI - Hormone receptor expression in invasive breast cancer among Korean women and
comparison of 3 antiestrogen receptor antibodies: a multi-institutional
retrospective study using tissue microarrays.
AB - Estrogen receptor (ER) and progesterone receptor (PR) are prognostic markers of
breast cancer and predictive markers of response to endocrine therapy. To
determine rates of ER and PR expression in invasive breast carcinoma among Korean
women, the Breast Pathology Study Group of the Korean Society of Pathologists
collected 1198 specimens of invasive breast carcinoma from 6 university
hospitals. Immunohistochemical analysis was carried out using 1 antibody against
PR and 3 antibodies against ER (1D5, 6F11, and SP1). Specimens were evaluated
using the semiquantitative Allred score (scores >2 were considered positive). A
total of 1077 cases were interpretable for all 3 anti-ER antibodies. ER
expression was positive in 68.5% of cases using SP1, in 59.6% using 1D5, and in
58.9% using 6F11. Of 1073 interpretable cases, PR expression was positive in
51.7% of cases. The frequency distribution of Allred scores revealed a bimodal
pattern (complete absence of staining or staining in most cells) for both ER and
PR. Patients with discordant results for 2 different ER antibodies showed a
median overall survival (between that of double-positive cancer and that of
double-negative cancer). Our results showed that the rate of hormone receptor
expression in breast carcinomas among Korean patients did not differ from that of
western patients. In addition, SP1 was the most sensitive antibody for
identifying ER expression in tumors. However, further evaluation is needed to
determine which antibody is the best for selecting patients with discordant
results who are likely to respond to endocrine therapy.
PMID- 23154770
TI - The distribution of microscopic melanoma metastases in sentinel lymph nodes:
implications for pathology protocols.
AB - The utility of sectioning at multiple levels in the histopathologic analysis of
sentinel lymph nodes (SLNs) for melanoma and the correlation of metastasis size
with risk of subsequent metastasis were investigated. Metastatic melanoma was
identified in SLNs from 91 of 475 (19%) melanoma patients with SLN sampling at
the Massachusetts General Hospital between 2004 and 2008. All SLNs were evaluated
by a 9-slide protocol: sets of MART-1, hematoxylin and eosin, and S100 stains at
3 distinct levels separated by 80 MUm. The location and size of the tumor
deposits were evaluated in the context of subsequent metastasis and overall
survival. Of the 91 patients with positive sentinel nodes, all 9 protocol slides
were available for review in 61 (67%). Eleven of 61 patients had no tumor present
in the first set of levels; 2 of these patients died of metastatic melanoma.
Patients in whom 11 or more tumor cells were detected in the sentinel node had a
greater chance of developing subsequent metastases when compared with patients in
whom 10 or fewer tumor cells were detected (P=0.05). Of those with either
metastases >2 mm in diameter or extracapsular extension, 50% developed metastases
beyond the SLN basin. Eliminating 1 of the 3 levels in the SLN detection protocol
would have led to a false-negative diagnosis in 18% of patients.
PMID- 23154771
TI - Molecular genetic evidence supporting the origin of somatic-type malignancy and
teratoma from the same progenitor cell.
AB - Occasionally, testicular teratomas have been observed to occur in association
with somatic-type malignancies. The latter may be seen in the primary germ cell
tumor or, more commonly, in metastases after chemotherapy. The molecular-genetic
relationship between the teratoma and the somatic-type malignancy is uncertain.
We examined 27 pairs of teratoma and somatic-type malignancies in metastatic
lesions. Interphase fluorescence in situ hybridization (FISH) analysis for 12p
overexpression and i(12p) was performed on formalin-fixed, paraffin-embedded
specimens. In addition, we compared the pattern of allelic loss between the
teratoma and the somatic-type malignancy using 4 microsatellite DNA markers
(D1S508, interferon-alpha, D13S317, and D18S543). A laser capture microdissection
technique was used to procure separate tumor components. The somatic-type
malignancies included adenocarcinoma (13), primitive neuroectodermal tumor (5),
sarcoma not otherwise specified (5), squamous cell carcinoma (1), chondrosarcoma
(1), and rhabdomyosarcoma (2). Twenty-one of 27 tumor pairs (78%) showed a
similar pattern of overexpression of 12p and/or i(12p) in both components. Two of
the 27 (7%) tumor pairs showed i(12p) only in the teratomatous component, and 4
of the 27 (15%) tumor pairs showed no abnormalities of chromosome 12p by
interphase FISH. Eight of the 12 (67%) tumor pairs analyzed had identical
patterns of loss of heterozygosity in both the teratoma and the somatic-type
malignancy. Four of the 12 (33%) paired cases showed additional allelic loss at
the interferon-alpha locus in the somatic-type malignant component only. Our data
show that the somatic-type malignancies that develop in germ cell tumors have the
same genetic alterations, detectable by FISH and loss of heterozygosity studies,
as in the corresponding teratoma. These findings support that the somatic-type
malignancies within metastases and the teratomas are clonally related and likely
derived from a common progenitor cell. Interphase FISH can be performed on
formalin-fixed, paraffin-embedded tissue and is a sensitive method for detecting
12p overexpression and i(12p), thus aiding in establishing the germ cell origin
of somatic-type malignancies in this context.
PMID- 23154772
TI - Histologic criteria and pitfalls in the diagnosis of lymphovascular invasion in
radical prostatectomy specimens.
AB - Lymphovascular invasion is a known independent prognostic factor in prostate
cancer. The objective of this study is to describe reliable morphologic features
for identification of lymphovascular invasion in prostatectomy specimens and
avoid misinterpretation of its mimickers. A total of 364 foci of lymphovascular
invasion were analyzed in 264 slides from 170 prostatectomies. The average tumor
volume was 25.5%. Tumor emboli were seen inside the tumor (8%), at the front edge
of the tumor (30%), separated from the tumor (32%), and distant from the tumor
(30%). Tumor emboli were more frequent per case and more often in an
extraprostatic location in lymph node-positive cases (P<0.05). One hundred thirty
four emboli were in a single thin-walled vessel, 227 were in a thin-walled vessel
next to an artery, and 3 were seen inside an artery. Twenty-eight tumor emboli
were attached to a vessel wall, 18 had proteinaceous material in the vascular
lumen, and 14 were surrounded by erythrocytes. The following mimickers were seen:
retraction artifact and perineural invasion-all cases; cancer impinging upon
vascular space-45 foci; tangential sections of endothelium-10 foci; displacement
of benign and collapsed malignant glands-16 and 27 foci, respectively; retraction
with erythrocytes-3 cases; intravascular degenerating tumor cells-3 foci;
malignant glands in atrophic ducts-4 foci; and myofibroblastic proliferation in
thrombosed vessels-2 foci. In 50 stained blocks, CD31 and D2-40 immunostaining
studies confirmed all lymphovascular invasions diagnosed by hematoxylin and eosin
staining and demonstrated emboli in 47 lymphatic and 16 blood vessels. In
summary, the current study identifies features of true lymphovascular invasion
and how to distinguish them from mimickers on routine hematoxylin and eosin
sections.
PMID- 23154773
TI - Conventional chondrosarcoma in a survivor of rhabdoid tumor: enlarging the
spectrum of tumors associated with SMARCB1 germline mutations.
AB - SMARCB1 germline mutations mainly predispose to rhabdoid tumors. However, less
aggressive tumors with a later onset have also been reported in a context of
SMARCB1 constitutional mutation-that is, schwannomatosis and meningiomatosis. No
other tumor type has formally been observed in such a context thus far. We report
on a patient treated for a thoracic malignant rhabdoid tumor at 8 years of age
who subsequently developed a mandibular conventional chondrosarcoma at 13 years
of age. Both tumors showed a loss of BAF47 expression. The malignant rhabdoid
tumor exhibited a large 22q11.2 deletion and an intragenic deletion of SMARCB1
(exons 1 to 3), thus leading to a biallelic inactivation. A 2.8 Mbp deletion
encompassing SMARCB1 was found in the germline. This context was a strong
incentive to investigate SMARCB1 alterations in the second tumor. As expected,
the chondrosarcoma showed the large 22q11.2 deletion but also an additional
c.243C>G(p.Tyr18X) premature stop codon in the remaining allele. This report
relates for the first time a pediatric conventional chondrosarcoma to the wide
family of SMARCB1-deficient tumors. Moreover, we report here the first case of
conventional chondrosarcoma arising in a context of constitutional SMARCB1
deletion and, thus, enlarge the spectrum of this tumor predisposition syndrome.
PMID- 23154774
TI - Malignant gastrointestinal neuroectodermal tumor showing overlapped
immunophenotype with synovial sarcoma: CD99 and SOX10 antibodies are useful in
differential diagnosis.
PMID- 23154776
TI - Human brain cancer studied by resonance Raman spectroscopy.
AB - The resonance Raman (RR) spectra of six types of human brain tissues are examined
using a confocal micro-Raman system with 532-nm excitation in vitro. Forty-three
RR spectra from seven subjects are investigated. The spectral peaks from
malignant meningioma, stage III (cancer), benign meningioma (benign), normal
meningeal tissues (normal), glioblastoma multiforme grade IV (cancer), acoustic
neuroma (benign), and pituitary adenoma (benign) are analyzed. Using a 532-nm
excitation, the resonance-enhanced peak at 1548 cm-1 (amide II) is observed in
all of the tissue specimens, but is not observed in the spectra collected using
the nonresonance Raman system. An increase in the intensity ratio of 1587 to 1605
cm-1 is observed in the RR spectra collected from meningeal cancer tissue as
compared with the spectra collected from the benign and normal meningeal tissue.
The peak around 1732 cm-1 attributed to fatty acids (lipids) are diminished in
the spectra collected from the meningeal cancer tumors as compared with the
spectra from normal and benign tissues. The characteristic band of spectral peaks
observed between 2800 and 3100 cm-1 are attributed to the vibrations of methyl
(?CH3) and methylene (?CH2?) groups. The ratio of the intensities of the spectral
peaks of 2935 to 2880 cm-1 from the meningeal cancer tissues is found to be
lower in comparison with that of the spectral peaks from normal, and benign
tissues, which may be used as a distinct marker for distinguishing cancerous
tissues from normal meningeal tissues. The statistical methods of principal
component analysis and the support vector machine are used to analyze the RR
spectral data collected from meningeal tissues, yielding a diagnostic sensitivity
of 90.9% and specificity of 100% when two principal components are used.
PMID- 23154778
TI - Experimental validation of a finite-difference model for the prediction of
transcranial ultrasound fields based on CT images.
AB - The prevalence of stroke worldwide and the paucity of effective therapies have
triggered interest in the use of transcranial ultrasound as an adjuvant to
thrombolytic therapy. Previous studies have shown that 120 kHz ultrasound
enhanced thrombolysis and allowed efficient penetration through the temporal
bone. The objective of our study was to develop an accurate finite-difference
model of acoustic propagation through the skull based on computed tomography (CT)
images. The computational approach, which neglected shear waves, was compared
with a simple analytical model including shear waves. Acoustic pressure fields
from a two-element annular array (120 and 60 kHz) were acquired in vitro in four
human skulls. Simulations were performed using registered CT scans and a source
term determined by acoustic holography. Mean errors below 14% were found between
simulated pressure fields and corresponding measurements. Intracranial peak
pressures were systematically underestimated and reflections from the
contralateral bone were overestimated. Determination of the acoustic impedance of
the bone from the CT images was the likely source of error. High correlation
between predictions and measurements (R(2) = 0.93 and R(2) = 0.88 for transmitted
and reflected waves amplitude, respectively) demonstrated that this model is
suitable for a quantitative estimation of acoustic fields generated during 40-200
kHz ultrasound-enhanced ischemic stroke treatment.
PMID- 23154780
TI - Mitochondrial DNA damage mediates hyperoxic dysmorphogenesis in rat fetal lung
explants.
AB - BACKGROUND: Numerous studies in cultured cells indicate that damage to
mitochondrial DNA (mtDNA) dictates cellular responses to oxidant stress, yet the
consequences of mtDNA damage have not been studied directly in the preterm lung.
OBJECTIVE: We sought to determine whether hyperoxia-induced fetal lung
dysmorphogenesis is linked to mtDNA damage and establish mtDNA repair as a
potential therapeutic approach for treating lung dysplasia in the preterm
neonate. METHODS: Hyperoxia-induced mtDNA damage was assessed by quantitative
alkaline gel electrophoresis in normoxic (3% O2) and hyperoxic (21% O2) fetal rat
lung explants. A fusion protein construct targeting the DNA repair enzyme
endonuclease III (Endo III) to the mitochondria was used to augment mtDNA repair.
Fetal lung branching and surfactant protein C (SFPTC) were assessed in these
tissues. RESULTS: Hyperoxia induced mtDNA damage in lung explants and was
accompanied by impaired branching morphogenesis and decreased SFPTC mRNA
expression. Treatment of lung explants with Endo III fusion protein prevented
hyperoxia-induced mtDNA damage and restored normal branching morphogenesis and
SFPTC mRNA expression. CONCLUSION: These findings support the concept that mtDNA
governs cellular responses to oxidant stress in the fetal lung and suggest that
modulation of mtDNA repair is a potential pharmacologic strategy in the
prevention of hyperoxic lung injury.
PMID- 23154781
TI - Risk score for predicting recurrence in patients with ischemic stroke: the
Fukuoka stroke risk score for Japanese.
AB - BACKGROUND: Currently, there are only a few risk scores to predict long-term
recurrence of ischemic stroke and no risk score has been developed for the Asian
population. The aim of the present study was to develop a new risk score to
predict 1-year recurrence in Japanese patients with ischemic stroke and compare
it with the other ones. METHODS: Data used in this analysis were extracted from
the Fukuoka stroke registry (FSR) database, including 3,067 Japanese patients who
experienced ischemic stroke. FSR is a multicenter, hospital-based, prospective
registry of Japanese patients with acute stroke. Associations between potential
clinical variables that could be involved in the increase of risk and recurrence
of ischemic stroke within 1 year after initial stroke onset were evaluated using
univariate and multivariate analyses. To calculate risk scores, weighted points
proportionally based on standardized coefficient values were assigned to
variables that were identified to be significant risks for recurrence by
multivariate analysis. The Hosmer-Lemeshow goodness-of-fit test was used to test
agreement between a predicted outcome using a model and an actual observed
outcome. Kaplan-Meier analysis was used to estimate average cumulative recurrence
rates within three risk groups. Intergroup comparisons in recurrence rate among
the risk groups were performed using a log-rank test. RESULTS: Univariate and
multivariate analyses identified nine significant predictors for 1-year
recurrence, to which we assigned the following points: age (65-74 years, 1 point;
>=75 years, 2 points), hypertension (1 point), diabetes mellitus (1 point),
smoker (1 point), atrial fibrillation (1 point), cardiac diseases (1 point),
chronic kidney disease (1 point), nonlacunar stroke (1 point), and previous
ischemic stroke (2 points). The Hosmer-Lemeshow goodness-of-fit test demonstrated
good agreement between the observed and predicted recurrence rate (chi(2) = 2.30,
p = 0.97). The ROC curve for the risk score models showed acceptable discriminant
power with a C-statistic of 0.636 (95% confidence interval: 0.573-0.698). Trends
toward increased risk of recurrence with higher scores were observed. The 1-year
recurrence rates were 2.93, 5.83 and 7.96% in low- (<=3 points), intermediate (4
5 points), and high-risk groups (>=6 points), respectively. Kaplan-Meier curves
with log-rank test showed a significant difference in recurrence among the three
risk groups (p < 0.0001). CONCLUSIONS: A new risk score was developed and
successfully validated. Our results suggest that this simple risk score enables
clinicians to assess 1-year recurrence risk in Japanese patients with ischemic
stroke.
PMID- 23154782
TI - Isolation of mouse mesenchymal stem cells on the basis of expression of Sca-1 and
PDGFR-alpha.
AB - Platelet-derived growth factor receptor alpha (PDGFR-alpha) and stem cell antigen
1 (Sca-1) have recently been identified as selective markers of mouse mesenchymal
stem cells (MSCs). PDGFR-alpha(+)Sca-1(+) (PalphaS) MSCs have augmented growth
potential and robust tri-lineage differentiation compared with standard culture
selected MSCs. In addition, the selective isolation of PalphaS MSCs avoids
cellular contamination that can complicate other methods. Here we describe in
detail our protocol to isolate PalphaS MSCs using flow cytometry. In brief, the
tibia and femora are isolated and crushed using a pestle and mortar. The crushed
bones are then chopped and incubated for 1 h at 37 degrees C in 20 ml of DMEM
containing 0.2% (wt/vol) collagenase. The cell suspension is filtered before red
blood cell lysis and incubated with the following antibodies: allophycocyanin
(APC)-conjugated PDGFR-alpha, FITC-conjugated Sca-1, phycoerythrin (PE)
conjugated CD45 and Ter119. Appropriate gates are constructed on a cell sorter to
exclude dead cells and lineage (CD45(+)Ter-119(+))-positive cells. Approximately
10,000 PalphaS MSCs may then be isolated per mouse. The total protocol takes ~7 h
to complete.
PMID- 23154783
TI - Exosome-mediated delivery of siRNA in vitro and in vivo.
AB - The use of small interfering RNAs (siRNAs) to induce gene silencing has opened a
new avenue in drug discovery. However, their therapeutic potential is hampered by
inadequate tissue-specific delivery. Exosomes are promising tools for drug
delivery across different biological barriers. Here we show how exosomes derived
from cultured cells can be harnessed for delivery of siRNA in vitro and in vivo.
This protocol first describes the generation of targeted exosomes through
transfection of an expression vector, comprising an exosomal protein fused with a
peptide ligand. Next, we explain how to purify and characterize exosomes from
transfected cell supernatant. Next, we detail crucial steps for loading siRNA
into exosomes. Finally, we outline how to use exosomes to efficiently deliver
siRNA in vitro and in vivo in mouse brain. Examples of anticipated results in
which exosome-mediated siRNA delivery is evaluated by functional assays and
imaging are also provided. The entire protocol takes ~3 weeks.
PMID- 23154785
TI - Bifunctional heterometallic Ln3+-Gd3+ (Ln = Eu, Tb) hybrid silica microspheres:
luminescence and MRI contrast agent property.
AB - A novel series of homometallic and heterometallic lanthanide (Eu(3+)(Tb(3+))
Gd(3+)) hybrid silica microspheres (EDTA-(Eu(Tb)-Gd)-TTA-SiO(2)) are synthesized
with 2-thenoyltrifluoroacetone (TTA) functionalized silane and
ethylenediaminetetraacetic acid (EDTA) by sol-gel process, whose physical
characterization are carried out and especially the luminescence and the magnetic
resonance imaging (MRI) contrast agent properties are discussed. These hybrids
present uniform silica microsphere morphology with particle size of 1 MUm.
Comparing to the homometallic hybrid silica microsphere EDTA-Ln-TTA-SiO(2)
without Gd(3+) ion, the heterometallic hybrid silica microspheres EDTA-Eu-Gd-TTA
SiO(2) exhibit stronger luminescent intensity, longer lifetime and higher
luminescent quantum efficiency, which is due to the fact that inert ion Gd(3+)
can enhance the luminescence of the Eu(3+) or Tb(3+) within the hybrid system. In
addition, the MRI relaxivity of the heterometallic lanthanide hybrid silica
microspheres in water is assessed, showing a lower T1 relaxation rate than
homometallic gadolinium hybrid one (EDTA-Gd-TTA-SiO(2)). Both of them show higher
T1 relaxation rate than the conventional Gd chelate of diethylenetriamine
pentaacetic acid. These bifunctional hybrid materials exhibit both luminescent
and MRI magnetic contrast agent properties, whose further investigation can be
expected to have potential application in practical fields such as optical
storage and sensors, etc.
PMID- 23154784
TI - The use of phage display to generate conformation-sensor recombinant antibodies.
AB - We describe a phage display approach that we have previously used to generate
conformation-sensor antibodies that specifically recognize and stabilize the
oxidized, inactive conformation of protein tyrosine phosphatase 1B (PTP1B). We
use a solution-based panning and screening strategy conducted in the presence of
reduced active PTP1B, which enriches antibodies to epitopes unique to the
oxidized form while excluding antibodies that recognize epitopes common to
oxidized and reduced forms of PTP1B. This strategy avoids conventional solid
phase immobilization owing to its inherent potential for denaturation of the
antigen. In addition, a functional screening strategy selects single-chain
variable fragments (scFvs) directly for their capacity for both specific binding
and stabilization of the target enzyme in its inactive conformation. These
conformation-specific scFvs illustrate that stabilization of oxidized PTP1B is an
effective strategy to inhibit PTP1B function; it is possible that this approach
may be applicable to the protein tyrosine phosphatase (PTP) family as a whole.
With this protocol, isolation and characterization of specific scFvs from immune
responsive animals should take ~6 weeks.
PMID- 23154786
TI - Detection of meniscal tears by arthroscopy and arthrotomy in dogs with cranial
cruciate ligament rupture: a retrospective, cohort study.
AB - OBJECTIVES: To evaluate and compare detection of meniscal tears associated with
cranial cruciate ligament insufficiency by either arthroscopy or arthrotomy.
METHODS: A retrospective, cohort study was completed with stifles (n = 531) of
dogs with cranial cruciate ligament rupture. Either a medial parapatellar
arthrotomy or an arthroscopy procedure was performed and groups were compared for
significant differences in meniscal tears detected using logistic regression
analysis. RESULTS: Arthroscopy was performed on 58.8% and arthrotomy on 41.2% of
the stifles. In total, 44.4% of the examined stifles had meniscal tears. Meniscal
tears were found in 38.8% of the stifles examined by arthrotomy, and 48.4% of
those examined by arthroscopy. Overall, the rate of detection of a meniscal tear
was significantly different (p = 0.019) between the groups, and meniscal tears
were observed more frequently by arthroscopy than by arthrotomy (odds ratio 1.54;
95% confidence interval 1.07 - 2.22). CLINICAL SIGNIFICANCE: These results
suggest that arthroscopy may be more sensitive than arthrotomy for detection of
meniscal pathology in clinical patients. However, these results must be
interpreted with caution since this was a retrospective study. Randomized
prospective clinical studies are required to further test this hypothesis.
PMID- 23154787
TI - Higher dietary intakes of potassium, calcium and magnesium are associated with a
reduced risk of developing vascular dementia.
PMID- 23154788
TI - Microlesion effect as a predictor of the effectiveness of subthalamic deep brain
stimulation for Parkinson's disease.
AB - BACKGROUND: Microlesion effect (MLE) is a commonly observed phenomenon after
electrode insertion into the subthalamic nucleus (STN) for deep brain stimulation
(DBS). OBJECTIVES: The aim of this study was to determine the presence of the MLE
in the early postoperative period and the relationship between MLE and STN DBS.
METHODS: 74 patients with Parkinson's disease were included in this study. Motor
symptoms were evaluated preoperatively, within 48 h after electrode implantation
and at 6 months with United Parkinson's Disease Rating Scale part III (UPDRS
III). According to the improvement level with MLE, all participants were
stratified into three groups: (1) less than 20%; (2) 20-40%, and (3) more than
40% in OFF medication states. The degree of improvement in UPDRS-III with DBS ON
for each MLE group was assessed at the 6-month follow-up. Regression analysis was
applied for the evaluation of the relationship between MLE and improvement with
DBS ON. RESULTS: Mean results in UPDRS-III with the MLE in ON and OFF medication
states were 22.1 +/- 10.5 and 42.1 +/- 14 points, respectively. At the 6-month
follow-up, with active stimulation, results tended to further ameliorate to 14.6
(59.4%) points in ON and 20.8 (55.3%) in OFF. Mean improvement in MLE groups
were: 33.6% group 1, 47.5% group 2 and 61.4% group 3. Regression analysis
revealed a positive correlation between the MLE and results at 6 months with DBS
ON. CONCLUSION: Results proved the presence of MLE in the early postoperative
period. Furthermore, a positive correlation between MLE and improvement degree
with active stimulation was observed.
PMID- 23154789
TI - Risk of bleeding complications after preoperative antiplatelet withdrawal versus
continuing antiplatelet drugs during transurethral resection of the prostate and
prostate puncture biopsy: a systematic review and meta-analysis.
AB - OBJECTIVE: To systematically evaluate the risk of antiplatelet drugs (APs) on
bleeding complications in urological surgery. METHODS: Studies were sought and
included in this review if they were clinical controlled trials and involved
transurethral resection of the prostate (TURP) and prostate puncture biopsy
(PPB), which compared preoperative AP withdrawal (control group) with continuing
APs (experimental group) and revealed bleeding complications as outcomes. A
literature search was conducted of the electronic databases PubMed, Ovid,
ScienceDirect and Embase for studies published between 1990 and 2012. Two
reviewers independently screened the studies for eligibility, evaluated the
quality and extracted the data from the eligible studies, with confirmation by
cross-checking. There was evidence of publication bias based on Egger's test and
funnel plot. Data were processed using Cochrane Review Manager 5.0 software.
RESULTS: Nine studies involving 3,145 cases met the inclusion criteria and were
included in the meta-analysis. The baselines of patients' characteristics were
comparable in all studies. The meta-analysis results showed that no differences
were found in risk of bleeding after (1) TURP (OR 1.26, 95% CI 0.80-2.00, p =
0.32) or (2) PPB (OR 0.89, 95% CI 0.45-1.76, p = 0.73). CONCLUSION: Preoperative
APs do not raise the risk of surgical bleeding complications in prostatectomy and
PPB. Because of few studies and small samples, more high-quality trials with
larger samples and longer follow-ups are proposed.
PMID- 23154790
TI - Surfactant modification of aggregation-induced emission material as biocompatible
nanoparticles: facile preparation and cell imaging.
AB - Water soluble and biocompatible fluorescent organic nanoparticles based on
aggregation-induced emission (AIE) material were facilely prepared by mixing AIE
material and surfactant. The utilization of such fluorescent organic
nanoparticles for cell imaging applications was further explored.
PMID- 23154791
TI - Dynamic tissue perfusion measurement: a new tool for characterizing renal
perfusion in renal cell carcinoma patients.
AB - INTRODUCTION: Renal cell carcinoma (RCC) is characterized by intense angiogenesis
with hyperexpression of proangiogenic factors. This study explored the potential
of dynamic tissue perfusion measurement (DTPM) to detect differences in tissue
perfusion between kidneys with RCC and corresponding healthy kidneys. PATIENTS
AND METHODS: 30 patients with unilateral, histologically confirmed RCC underwent
DTPM by color Doppler ultrasound. Before scheduled surgery, Doppler ultrasound
data were acquired from four transverse areas of the affected kidney and the
contralateral healthy kidney. Doppler ultrasound data were recorded over a 10
second period and characteristic tissue perfusion parameters were determined.
RESULTS: The kidneys with RCC displayed characteristic changes in perfusion
parameters. A significant increase in signal intensity and a significant decrease
in flow resistance were noted. A combination of several DTPM parameters was used
to distinguish correctly between kidneys bearing RCC or healthy kidneys with up
to 75% accuracy. There was no association between the perfusion parameters and
the pathological characteristics of the respective tumors. CONCLUSIONS: DTPM is a
promising tool for the evaluation of whole-organ tissue perfusion. This study
demonstrates the feasibility of performing DTPM measurements in kidneys bearing
RCC lesions. In tumors that are characterized by extensive neovascularization,
this method has the potential to be a valuable diagnostic tool.
PMID- 23154792
TI - Directed surface attachment of nanomaterials via coiled-coil-driven self
assembly.
AB - Numerous nanoscale devices and materials have been fabricated in recent years
using a variety of biological scaffolds. However, the interfacing of these
devices and materials into existing circuits and ordered arrays has proved
problematic. Here, we describe a simple solution to this problem using self
assembly of the peptide coiled-coil heterodimer ACID:BASE to immobilize M13
bacteriophage particles to specific locations on a patterned gold surface.
Surface plasmon resonance demonstrated that free ACID peptides will assemble onto
a surface derivatized with BASE. We then displayed the ACID peptide on the pIX
coat protein of M13 and showed that these phage particles permit formation of the
coiled-coil resulting in specific surface attachment. The ACID:immobilized BASE
affinities appear to be similar for free peptide and phage-displayed ACID.
Finally, we fabricated two gold electrodes, separated by a 200 nm gap, coated one
of them with BASE and showed that this allows localization of the M13:ACID onto
the functionalized electrode.
PMID- 23154793
TI - Postoperative cerebral white matter damage associated with cerebral
hyperperfusion and cognitive impairment after carotid endarterectomy: a diffusion
tensor magnetic resonance imaging study.
AB - BACKGROUND: Cerebral hyperperfusion after carotid endarterectomy (CEA), even when
asymptomatic, often impairs cognitive function. However, conventional magnetic
resonance (MR) imaging rarely demonstrates structural brain damage associated
with postoperative cognitive impairment. MR diffusion tensor imaging (DTI) is
potentially more sensitive for detection of white matter damage. Among the common
parameters derived by DTI, fractional anisotropy (FA) is a marker of tract
integrity, and mechanical disruption of axonal cylinders and loss of continuity
of myelin sheaths may be responsible for reduced FA in white matter. The purpose
of the present study was to determine whether postoperative cerebral white matter
damage that can be detected by FA derived by DTI is associated with cerebral
hyperperfusion after CEA and correlates with postoperative cognitive impairment.
METHODS: In 70 patients undergoing CEA for ipsilateral internal carotid artery
stenosis (>=70%), cerebral blood flow (CBF) was measured using single-photon
emission computed tomography (SPECT) before and immediately after CEA and on
postoperative day 3. FA values in cerebral white matter were assessed using DTI
before and 1 month after surgery. These values were normalized and analyzed using
statistical parametric mapping 5. In each corresponding voxel in the pre- and
postoperative normalized FA maps of each patient, a postoperative FA value minus
a preoperative FA value was calculated, and a voxel with postoperatively reduced
FA was defined based on data obtained from healthy volunteers. The number of
voxels with postoperatively reduced FA was calculated and defined as the volume
with postoperatively reduced FA. Neuropsychological testing, consisting of the
Wechsler Adult Intelligence Scale Revised, the Wechsler Memory Scale and the Rey
Osterreith Complex Figure test, was also performed preoperatively and after the
first postoperative month. Postoperative cognitive impairment on
neuropsychological testing in each patient was defined based on data obtained
from patients with asymptomatic unruptured cerebral aneurysms. RESULTS: Post-CEA
hyperperfusion on brain perfusion SPECT (CBF increase >=100% compared with
preoperative values) and postoperative cognitive impairment on neuropsychological
testing were observed in 11 (16%) and 9 patients (13%), respectively. The volume
with postoperatively reduced FA in cerebral white matter ipsilateral to surgery
was significantly greater in patients with post-CEA hyperperfusion than in those
without (p < 0.0001). This volume in cerebral white matter ipsilateral to surgery
was also significantly associated with postoperative cognitive impairment (95%
confidence interval, 1.559-8.853; p = 0.0085). CONCLUSIONS: Cerebral
hyperperfusion after CEA results in postoperative cerebral white matter damage
that correlates with postoperative cognitive impairment.
PMID- 23154794
TI - Switchable skin window induced by optical clearing method for dermal blood flow
imaging.
AB - Optical imaging techniques have shown tremendous potential for assessing
cutaneous microcirculation, but the imaging depth and contrast is limited by the
strong scattering of skin. Current skin windows have to be fulfilled by surgical
operation and suffer from some side effects. In this study, a switchable skin
window was developed by topical application of an optical clearing agent (OCA)
and saline on rat skin in vivo. The validity of the skin window was evaluated by
the laser speckle contrast imaging technique, and the safety of OCA to the body
was tested through histologic examinations. The results indicated that
administration of OCA or saline on rat skin in vivo can open or close the window
of skin repeatedly for three days. With the repair effect of hyaluronic acid and
Vaseline, it is able to repeatedly visualize the dermal blood vessels and flow
distribution. Long-term observation shows that there is no abnormal reflection in
micro-structure, body weight, organ coefficients, histopathologic lesions, or
toxic reactions compared with a control group. This switchable window will
provide an effective tool not only for cutaneous microcirculation with laser
speckle contrast imaging, but also for diagnosis and treatment of peripheral
vascular diseases, including tumor research with various optical imaging
techniques.
PMID- 23154796
TI - Thalamotomy as a treatment option for tremor after ineffective deep brain
stimulation.
AB - BACKGROUND: As the number of deep brain stimulation (DBS) surgeries increases,
complications from malpositioned electrodes, tolerance to stimulation and loss of
efficacy have also increased. Our objective was to assess thalamotomy as a
salvage treatment option after ineffective DBS. METHODS: A retrospective chart
analysis of patients who underwent ipsilateral stereotactic thalamotomy after an
ineffective ventrointermediate nucleus DBS procedure was undertaken. Patient
outcome was based on follow-up visit chart notes, and a nonvalidated patient
telephone questionnaire to assess patients' perception of tremor and functional
ability after thalamotomy. RESULTS: Six patients with essential tremor and 1 with
tremor-predominant Parkinson's disease met our inclusion criteria. Thalamotomies
were undertaken for ineffective DBS due to dysarthria and paresthesias with
programming in 2 patients, tremor that failed to respond to increased DBS despite
a lack of side effects in 2 patients, malpositioned electrode in 2 patients, and
sudden loss of DBS efficacy following eye surgery in 1 patient. Following
thalamotomy, 3 patients reported improvement in symptoms and function, 3 patients
reported improvement in symptoms that were not reflected in functional
improvement, and 1 patient reported no improvement in symptoms or function.
CONCLUSION: Thalamotomy may provide a viable salvage solution in patients who
fail to respond to DBS due to complications such as malpositioned electrodes,
tolerance to stimulation or loss of efficacy.
PMID- 23154795
TI - Impact of margin size on the predicted risk of radiogenic second cancers
following proton arc therapy and volumetric modulated arc therapy for prostate
cancer.
AB - We previously determined that the predicted risk of radiogenic second cancer in
the bladder and rectum after proton arc therapy (PAT) was less than or equal to
that after volumetric modulated arc therapy (VMAT) with photons, but we did not
consider the impact of margin size on that risk. The current study was thus
conducted to evaluate margin size's effect on the predicted risks of second
cancer for the two modalities and the relative risk between them. Seven treatment
plans with margins ranging from 0 mm in all directions to 6 mm posteriorly and 8
mm in all other directions were considered for both modalities. We performed risk
analyses using three risk models with varying amounts of cell sterilization and
calculated ratios of risk for the corresponding PAT and VMAT plans. We found that
the change in risk with margin size depended on the risk model but that the
relative risk remained nearly constant with margin size, regardless of the amount
of cell sterilization modeled. We conclude that while margin size influences the
predicted risk of a second cancer for a given modality, it appears to affect both
modalities in roughly equal proportions so that the relative risk between PAT and
VMAT is approximately equivalent.
PMID- 23154799
TI - Direct coupling of nitriles and aniline to form the triazapentadiene species
[upper bond 1 start]Rh(III){NH=C(R)N(Ph)C(R=N[upper bond 1 end]H}.
AB - The facile and high-yield reaction between aniline and cis-positioned nitriles of
[((t)bpy)(2)Rh(NCR)(2)][OTf](3) [R = Me (2), Ph (3); (t)bpy = 4,4'-di-tert-butyl
2,2'-bipyridine; OTf = CF(3)SO(3)(-)] produces the Rh(III)-triazapentadiene
species [((t)bpy)(2)[upper bond 1 start]Rh{NH=C(R)N(Ph)C(R=N[upper bond 1
end]H}][OTf](3) [R = Me (4), Ph (5)]. It represents the first example of direct
coupling between two RCN ligands and a primary amine to form this type of
metallacycle. X-ray structures of 2 and 4 are reported.
PMID- 23154808
TI - Evolution of genetic and genomic features unique to the human lineage.
AB - Given the unprecedented tools that are now available for rapidly comparing
genomes, the identification and study of genetic and genomic changes that are
unique to our species have accelerated, and we are entering a golden age of human
evolutionary genomics. Here we provide an overview of these efforts, highlighting
important recent discoveries, examples of the different types of human-specific
genomic and genetic changes identified, and salient trends, such as the
localization of evolutionary adaptive changes to complex loci that are highly
enriched for disease associations. Finally, we discuss the remaining challenges,
such as the incomplete nature of current genome sequence assemblies and
difficulties in linking human-specific genomic changes to human-specific
phenotypic traits.
PMID- 23154809
TI - Adaptive evolution: evaluating empirical support for theoretical predictions.
AB - Adaptive evolution is shaped by the interaction of population genetics, natural
selection and underlying network and biochemical constraints. Variation created
by mutation, the raw material for evolutionary change, is translated into
phenotypes by flux through metabolic pathways and by the topography and dynamics
of molecular networks. Finally, the retention of genetic variation and the
efficacy of selection depend on population genetics and demographic history.
Emergent high-throughput experimental methods and sequencing technologies allow
us to gather more evidence and to move beyond the theory in different systems and
populations. Here we review the extent to which recent evidence supports long
established theoretical principles of adaptation.
PMID- 23154812
TI - Surgical management of radial head luxation in a dog using an external skeletal
traction device.
AB - A five-month-old Airedale Terrier was presented with a history of right thoracic
limb lameness. Clinical and radiographic examinations revealed caudolateral
luxation of the right radial head. Surgical intervention involved an oblique
proximal radial osteotomy and gradual craniomedial traction of the radial head
using an external skeletal fixator (ESF) incorporating a traction device. The
radial head was gradually reduced over 16 days. After radiographic confirmation
of appropriate radial head reduction, a consolidation phase followed, with
removal of the traction ESF after 24 days. Follow-up radiographs documented
remodelling of the radial head. Clinical follow-up three years postoperatively
revealed nearly normal ground reaction forces. Activity was unrestricted and
there was no requirement for analgesic medications.
PMID- 23154811
TI - Asymmetric synthesis of 2,3-dihydroquinolin-4-one derivatives catalyzed by a
chiral bisguanidium salt.
AB - Worth its salt: An orgnaocatalytic asymmetric intramolecular aza-Michael reaction
and one-pot bromination reaction of activated alpha,beta-unsaturated ketones have
been realized using a chiral bisguanidium salt. Optically enriched 2-aryl- and 2
alkyl-substituted dihydroquinones and brominated dihydroquinones could be
obtained (up to 99% yield and 99% ee for the aza-Michael reaction; and up to 95%
yield, 96:4 d.r., and 95% ee for the bromination reaction).
PMID- 23154810
TI - Human mitochondrial DNA: roles of inherited and somatic mutations.
AB - Mutations in the human mitochondrial genome are known to cause an array of
diverse disorders, most of which are maternally inherited, and all of which are
associated with defects in oxidative energy metabolism. It is now emerging that
somatic mutations in mitochondrial DNA (mtDNA) are also linked to other complex
traits, including neurodegenerative diseases, ageing and cancer. Here we discuss
insights into the roles of mtDNA mutations in a wide variety of diseases,
highlighting the interesting genetic characteristics of the mitochondrial genome
and challenges in studying its contribution to pathogenesis.
PMID- 23154813
TI - A new paradigm for the diagnosis and management of unknown primary tumors of the
head and neck: a role for transoral robotic surgery.
AB - OBJECTIVES/HYPOTHESIS: In 2% to 3% of patients with cancer metastatic to cervical
lymph nodes, a primary tumor will not be found despite exhaustive diagnostic
efforts. The treatment for these patients includes cervical lymphadenectomy
followed by radiation to areas with increased risk of harboring a mucosal
primary. Wide-field radiation therapy increases the incidence of xerostomia and
dysphagia. Localizing a primary tumor has thus both therapeutic and quality-of
life implications, allowing possible complete surgical excision, concentrated
radiation therapy, and potential deintensification of adjuvant therapy. With
improved visualization and freedom of motion, transoral robotic surgery (TORS) is
an innovative surgical modality that allows resection of oropharyngeal subsites
with minimal morbidity. STUDY DESIGN: Retrospective chart review. METHODS: Ten
patients with unknown primary tumors of the head and neck were identified. All
patients underwent a cervical biopsy, positron-emission tomography/computed
tomography, formal endoscopy, and bilateral tonsillectomy. When the initial
endoscopy and biopsies did not localize a primary tumor, all patients underwent
transoral robotic base of tongue resection. RESULTS: Evaluation of the patients'
oropharyngeal mucosa using the robot did not reveal an obvious lesion and no
palpable tumors were appreciated in the resected specimens. In 9/10 (90%)
patients, pathologic examination revealed invasive squamous cell carcinoma (SCCA)
with a mean diameter of 0.9 cm. CONCLUSIONS: Unknown primary SCCA presents a
diagnostic challenge to the head and neck surgeon. We present a small series of
tumors that would have been treated as unknown primaries under traditional
diagnostic and therapeutic algorithms. TORS base of tongue resection identified
primary tumors in 90% patients with minimal morbidity.
PMID- 23154815
TI - Effects of deep brain stimulation in the caudal zona incerta on verbal fluency.
AB - BACKGROUND: Deep brain stimulation (DBS) of the caudal zona incerta (cZi) is a
relatively unexplored and promising treatment in patients with severe essential
tremor (ET). Preliminary data further indicate that the ability to produce
language may be slightly affected by the treatment. OBJECTIVE: To evaluate the
effects on verbal fluency following cZi DBS in patients with ET. METHOD:
Seventeen consecutive patients who had undergone DBS of the cZi for ET were
tested regarding verbal fluency before surgery, 3 days after surgery and after 1
year. Ten patients were also evaluated by comparing performance on versus off
stimulation after 1 year. RESULTS: The total verbal fluency score decreased
slightly, but significantly, from 22.7 (SD = 10.9) before surgery to 18.1 (SD =
7.5) 3 days after surgery (p = 0.036). After 1 year the score was
nonsignificantly decreased to 20.1 (SD = 9.7, p = 0.2678). There was no
detectable difference between stimulation on and off after 1 year. CONCLUSION:
There was a tendency of an immediate and mostly transient postoperative decline
in verbal fluency following cZi DBS for ET. In some of the patients this
reduction was, however, more pronounced and also sustained over time.
PMID- 23154814
TI - Angiotensin II induces TSLP via an AT1 receptor/NF-KappaB pathway, promoting Th17
differentiation.
AB - BACKGROUND: Adaptive immunity plays a critical role in atherosclerosis and
hypertension. T helper 17 (Th17) cells, as a new T-cell lineage, are involved in
cardiovascular diseases. Dendritic cells (DCs) are the professional antigen
presenting cells with the pivotal role in orchestrating adaptive immunity. Thymic
stromal lymphopoietin (TSLP) can activate DCs and trigger adaptive immune
responses. What the role of TSLP in atherosclerosis and hypertension has not been
investigated. METHODS AND RESULTS: We measured the expression of TSLP in primary
rat vascular smooth muscle cells (VSMCs) exposed to angiotensin II (Ang II) and
evaluated the capacity of TSLP induced by Ang II to induce the differentiation of
Th17 Cells. We then sought to identify the involved upstream regulatory
mechanisms. We found that VSMCs express TSLP in response to Ang II in an AT1
receptor/NF-KappaB manner. TSLP can induce the differentiation of Th17 Cells by
triggering DCs. CONCLUSION: Through DC activation, Ang II-induced TSLP enhances
Th17-driven immune response in atherosclerosis and hypertension.
PMID- 23154816
TI - High yield transfer of ordered nanowire arrays into transparent flexible polymer
films.
AB - The factors affecting transfer of nanowire arrays from their substrates into
flexible PDMS films have been systematically investigated. Experiments were
carried out on gallium phosphide nanowires with a standard length of 10 MUm with
varying pitch (0.2-1.5 MUm). The important factors were found to be penetration
of the PDMS within the nanowire arrays and the strength/rigidity of the PDMS
film. The PDMS penetration between wires in the arrays is affected by both the
viscosity of the PDMS solution and the presence of air pockets trapped within
nanowire arrays, particularly at small pitches. Dilution with hexane and curing
in a vacuum desiccator solve the wire penetration problem, and an increase in
cure/base ratio increases the rigidity and strength of the PDMS. The procedures
for preparation and deposition of the PDMS solution are optimized and a high
yield, up to 95%, of wire transfer across a range of nanowire pitches has been
obtained.
PMID- 23154817
TI - Enhanced photocoagulation with catheter-based diffusing optical device.
AB - A novel balloon catheter-based diffusing optical device was designed and
evaluated to assist in treating excessive menstrual bleeding. A synthetic fused
silica fiber was micro-machined precisely to create scattering segments on a 25
mm long fiber tip for uniform light distribution. A visible wavelength
(lambda=532 nm) was used to specifically target the endometrium due to the high
vascularity of the uterine wall. Optical simulation presented 30% wider
distribution of photons along with approximately 40% higher irradiance induced by
addition of a glass cap to the diffuser tip. Incorporation of the optical
diffuser with a polyurethane balloon catheter considerably enhanced coagulation
depth and area (i.e., 3.5 mm and 18.9 cm2 at 1 min irradiation) in tissue in
vitro. The prototype device demonstrated the coagulation necrosis of 2.8+/-1.2
mm (n=18) and no thermal damage to myometrium in in vivo caprine models. A
prototype 5 cm long balloon catheter-assisted optical diffuser was also evaluated
with a cadaveric human uterus to confirm the coagulative response of the uterine
tissue as well as to identify the further design improvement and clinical
applicability. The proposed catheter-based diffusing optical device can be a
feasible therapeutic tool to photocoagulate endometrial cell layers in an
efficient and safe manner.
PMID- 23154818
TI - Diagnosis: clinician's gut feeling helps detect children with serious infection.
PMID- 23154819
TI - Microfluidic ultralow interfacial tensiometry with magnetic particles.
AB - We describe a technique that measures ultralow interfacial tensions using
paramagnetic spheres in a co-flow microfluidic device designed with a magnetic
section. Our method involves tuning the distance between the co-flowing interface
and the magnet's center, and observing the behavior of the spheres as they
approach the liquid-liquid interface-the particles either pass through or are
trapped by the interface. Using threshold values of the magnet-to-interface
distance, we make estimates of the two-fluid interfacial tension. We demonstrate
the effectiveness of this technique for measuring very low interfacial tensions,
O(10(-6)-10(-5)) N m(-1), by testing solutions of different surfactant
concentrations, and we show that our results are comparable with measurements
made using a spinning drop tensiometer.
PMID- 23154822
TI - Surgical repair of a tibial fracture in a two-week-old grey seal (Halichoerus
grypus).
AB - OBJECTIVE: To report the successful management of a suspected infected tibial
fracture in a common grey seal. STUDY DESIGN: Case report. ANIMAL: Female common
grey seal (Halichoerus grypus), 2 weeks old, 20 kg. METHODS: A closed, complete,
transverse fracture of the left tibial distal diaphysis was debrided, reduced and
stabilized using a string-of-pearls (SOP) locking plate covered with
polymethylmethacrylate impregnated with gentamicin. Fracture of the ipsilateral
fibula was left untreated. Postoperative radiographs were obtained immediately,
and at 10 days, three weeks, and six weeks post-surgery, and a computed
tomographic examination was performed 2.5 months post- surgery. A species
specific progressive rehabilitation programme was conducted. RESULTS: Bone
healing of both fractures and absence of injury of the distal tibial growth plate
were evident on the 2.5 month follow-up examination, and also full range-of
motion of the flipper was preserved and no lameness or difficulty with swimming
and hunting were detected. On computed tomography, signs of chronic left
coxofemoral and ilial wing trauma were incidentally detected. The seal was
released three months postoperatively. CONCLUSION: A transverse infected distal
fracture of the tibia and fibula in a young common grey seal was successfully
managed with the combination of single SOP plating of the tibia, local antibiotic
release and a specific rehabilitation programme. CLINICAL RELEVANCE: Surgical
treatment of a long-bone fracture in a wild immature grey seal was successful
with a combination of techniques adapted to the species.
PMID- 23154823
TI - Rolled-up magnetic microdrillers: towards remotely controlled minimally invasive
surgery.
AB - Self-folded magnetic microtools with sharp ends are directed at enabling drilling
and related incision operations of tissues, ex vivo, in a fluid with a viscosity
similar to that of blood. These microtools change their rotation from a
horizontal to a vertical one when they are immersed into a rotational magnetic
field. Novel self-assembly paradigms with magnetic materials can enable the
creation of remotely controlled and mass-produced tools for potential
applications in minimally invasive surgery.
PMID- 23154824
TI - Nanoepitaxy of GaAs on a Si(001) substrate using a round-hole nanopatterned SiO2
mask.
AB - GaAs is grown by metal-organic vapor-phase epitaxy on a 55 nm round-hole
patterned Si substrate with SiO(2) as a mask. The threading dislocations, which
are stacked on the lowest energy facet plane, move along the SiO(2) walls,
reducing the number of dislocations. The etching pit density of GaAs on the 55 nm
round-hole patterned Si substrate is about 3.3 * 10(5) cm(-2). Compared with the
full width at half maximum measurement from x-ray diffraction and
photoluminescence spectra of GaAs on a planar Si(001) substrate, those of GaAs on
the 55 nm round-hole patterned Si substrate are reduced by 39.6 and 31.4%,
respectively. The improvement in material quality is verified by transmission
electron microscopy, field-emission scanning electron microscopy, Hall
measurements, Raman spectroscopy, photoluminescence, and x-ray diffraction
studies.
PMID- 23154827
TI - Dissection of the potential characteristic of miRNA-miRNA functional synergistic
regulations.
AB - MicroRNAs (miRNAs), as master gene regulators, control various cellular processes
through the post-transcriptional regulatory network. miRNA synergetic regulations
are gradually identified by experimental or computational evidence. However, the
potential characteristic underlying miRNA synergism remains a mystery. Based on
the constructed miRNA-miRNA functional synergetic networks (MFSNs), we attempted
to systematically dissect their potential characteristic from three levels:
sequence, secondary structure and transcriptional regulation. As a result,
functional synergetic miRNA pairs exhibit high seed sequence and secondary
structure similarity, and these characteristics are significant even when
analyzing synergism between miRNAs from different families. Additionally,
synergistic miRNAs tend to share a common transcriptional regulatory mechanism. A
striking property of miRNAs with both synergism and co-regulation is their
central roles in the MFSN, and tends to be involved in complex diseases. The
potential characteristic in these three levels are validated to be robust by
analyzing different MFSNs. Finally, we identified four tightly cooperative miRNA
sub-networks which are also co-regulated by transcription factors, all of which
regulate many important functions, including embryonic development, oncogenesis
and micromanagement of metastasis, helping us to further understand the
"language" of transcriptional and post-transcriptional regulation from a cross
layer view.
PMID- 23154825
TI - Lumican regulates ventilation-induced epithelial-mesenchymal transition through
extracelluar signal-regulated kinase pathway.
AB - BACKGROUND: Mechanical ventilation used in patients with acute lung injury can
damage pulmonary epithelial cells through production of inflammatory cytokines
and excess deposition of the extracellular matrix protein lumican. Lumican
participates in macrophage inflammatory protein (MIP)-2 and transforming growth
factor-beta1 (TGF-beta1) signaling during the fibroproliferative phase of acute
lung injury, which involves a process of epithelial-mesenchymal transition (EMT).
The mechanisms regulating interactions between mechanical ventilation and lung
injury are unclear. We hypothesized that lung damage and EMT by high tidal volume
(Vt) mechanical stretch causes upregulation of lumican that modulates MIP-2 and
TGF-beta1 through the extracellular signal-regulated kinase (ERK) 1/2 pathway.
METHODS: Male C57BL/6 mice (either wild type or lumican null) aged 3 months and
weighing between 25 and 30 g were exposed to low Vt (6 mL/kg) or high Vt (30
mL/kg) mechanical ventilation with room air for 2 to 8 h. Nonventilated mice were
used as control subjects. RESULTS: We found that high Vt mechanical ventilation
increased microvascular permeability, neutrophil influx, production of free
radicals, MIP-2 and TGF-beta1 proteins, positive staining of alpha-smooth muscle
actin and S100A4/fibroblast-specific protein-1, Masson trichrome staining and
extracellular collagen, and activation of lumican and ERK1/2 in wild-type mice.
Decreased staining of the epithelial marker E-cadherin was also observed.
Mechanical stretch-augmented EMT was attenuated with lumican-deficient mice and
pharmacologic inhibition of ERK1/2 activity by PD98059. CONCLUSIONS: The data
suggest that lumican promotes high Vt mechanical ventilation-induced lung injury
and EMT through the activation of the ERK1/2 pathway.
PMID- 23154829
TI - AN AUTOMATIC FEATURE BASED MODEL FOR CELL SEGMENTATION FROM CONFOCAL MICROSCOPY
VOLUMES.
AB - We present a model for the automated segmentation of cells from confocal
microscopy volumes of biological samples. The segmentation task for these images
is exceptionally challenging due to weak boundaries and varying intensity during
the imaging process. To tackle this, a two step pruning process based on the Fast
Marching Method is first applied to obtain an over-segmented image. This is
followed by a merging step based on an effective feature representation. The
algorithm is applied on two different datasets: one from the ascidian Ciona and
the other from the plant Arabidopsis. The presented 3D segmentation algorithm
shows promising results on these datasets.
PMID- 23154830
TI - NIR light controlled photorelease of siRNA and its targeted intracellular
delivery based on upconversion nanoparticles.
AB - The most notable role of small interfering RNA (siRNA) is in RNA interference
(RNAi) and post-transcriptional gene silencing, which leads to a surge of
interest in RNAi for both biomedical research and therapeutic applications.
However, "naked" siRNA cannot cross cellular membranes freely because of highly
negative charges which limits its utility for gene therapy. In this work, a
system of near-infrared (NIR) light-induced siRNA release from silica coated
upconversion nanoparticles (Si-UCNPs) is presented. These Si-UCNPs were
functionalized with cationic photocaged linkers through covalent bonding, which
could effectively adsorb anionic siRNA through electrostatic attractions and were
easily internalized by living cells. Upon NIR light irradiation, the photocaged
linker on the Si-UCNPs surface could be cleaved by the upconverted UV light and
thus initiated the intracellular release of the siRNA. The in vitro agarose gel
electrophoresis and intracellular imaging results indicated that the Si-UCNPs
based gene carrier system allowed effective siRNA delivery and the applications
of NIR light instead of direct high energy UV irradiation may greatly guarantee
less cell damage.
PMID- 23154832
TI - Myositis ossificans circumscripta of the triceps muscle in a Rottweiler dog.
AB - A 20-month-old male Rottweiler dog was presented with the complaint of chronic
right forelimb lameness that was unresponsive to conservative treatment. Physical
examination allowed for the topographical identification of the source of the
problem as a firm enlargement of the soft tissues that was partially movable from
humeral bone and compatible with an alteration of the triceps brachii muscle.
Radiographic images showed signs that were highly suggestive of myositis
ossificans. Computed tomography allowed for a more accurate characterization of
the lesion, to exclude involvement of the elbow joint and humeral bone, and to
localize anatomically the lesion in the caput accessorium and longum of the
triceps brachii muscle. Surgical excision of the ossified portion of the triceps
muscle was performed. Histological examination of the excised tissue
substantiated the diagnosis of myositis ossificans. A one year clinical and
radiographic follow-up examination showed a complete recovery, with no evidence
of complications or recurrence. Despite myositis ossificans in dogs having
previously been identified in the hindlimbs, this case of myositis ossificans
circumscripta of the triceps muscle suggests that it may also occur in the
muscles of the forelimb.
PMID- 23154831
TI - Acquired hypermethylation of the P16INK4A promoter in abdominal paraganglioma:
relation to adverse tumor phenotype and predisposing mutation.
AB - Recurrent alterations in promoter methylation of tumor suppressor genes (TSGs)
and LINE1 (L1RE1) repeat elements were previously reported in pheochromocytoma
and abdominal paraganglioma. This study was undertaken to explore CpG methylation
abnormalities in an extended tumor panel and assess possible relationships
between metastatic disease and mutation status. CpG methylation was quantified by
bisulfite pyrosequencing for selected TSG promoters and LINE1 repeats.
Methylation indices above normal reference were observed for DCR2 (TNFRSF10D),
CDH1, P16 (CDKN2A), RARB, and RASSF1A. Z-scores for overall TSG, and individual
TSG methylation levels, but not LINE1, were significantly correlated with
metastatic disease, paraganglioma, disease predisposition, or outcome. Most
strikingly, P16 hypermethylation was strongly associated with SDHB mutation as
opposed to RET/MEN2, VHL/VHL, or NF1-related disease. Parallel analyses of
constitutional, tumor, and metastasis DNA implicate an order of events where
constitutional SDHB mutations are followed by TSG hypermethylation and 1p loss in
primary tumors, later transferred to metastatic tissue. In the combined material,
P16 hypermethylation was prevalent in SDHB-mutated samples and was associated
with short disease-related survival. The findings verify the previously reported
importance of P16 and other TSG hypermethylation in an independent tumor series.
Furthermore, a constitutional SDHB mutation is proposed to predispose for an
epigenetic tumor phenotype occurring before the emanation of clinically
recognized malignancy.
PMID- 23154833
TI - Surviving the macrophage: tools and tricks employed by Mycobacterium
tuberculosis.
AB - Mycobacterium tuberculosis has evolved to withstand one of the most inhospitable
cells within the human body, namely the macrophage, a cell that is normally
geared toward the destruction of any invading microbe. How M. tuberculosis
achieves this is still incompletely understood; however, a number of mechanisms
are now known that provide advantages to M. tuberculosis for its survival and
proliferation inside the macrophage. While some of these mechanisms are mediated
by factors released by M. tuberculosis, others rely on host components that are
being hijacked to benefit survival of M. tuberculosis within the macrophage as
well to avoid the generation of an effective immune response. Here, we describe
several of these mechanisms, also pointing out the potential usage of this
knowledge toward the development of novel strategies to treat tuberculosis.
Furthermore, we attempt to put the 'macrophage niche' into context with other
intracellular pathogens and discuss some of the generalities as well as
specializations that M. tuberculosis employs to survive.
PMID- 23154834
TI - Patient and facility characteristics associated with benzodiazepine prescribing
for veterans with PTSD.
AB - OBJECTIVE: Practice guidelines used in the Veterans Health Administration (VHA)
caution against benzodiazepine use by veterans with posttraumatic stress disorder
(PTSD) because of inefficacy and safety concerns. Although use has declined, the
VHA prescription rate is >=30% nationally. To inform intervention design, this
study examined patient- and facility-level correlates of benzodiazepine
prescribing. METHODS: This cross-sectional study used 2009 national
administrative VHA data to identify veterans with PTSD, benzodiazepine
prescriptions, and various patient and facility characteristics. Correlates of
benzodiazepine prescribing were determined with multivariable hierarchical logit
models. RESULTS: Among 137 VHA facilities, 495,309 veterans with PTSD were
identified, and 150,571 (30.4%) received a benzodiazepine prescription. Patient
characteristics independently associated with benzodiazepine use included female
gender, age >=30 years, rural residence, service-connected disability >=50%,
Vietnam-era service, duration of PTSD diagnosis, and a comorbid anxiety disorder.
However, case-mix adjustment for these variables accounted for <1% of prescribing
variation. Facility characteristics independently associated with higher use
included lower PTSD visit volume, higher rates of duplicate prescribing
(concurrent use of more than one drug from a class), and lower rates of trazodone
prescribing. These findings were corroborated in replication analyses.
CONCLUSION: The ultimate goal is to ensure consistent access to guideline
concordant PTSD treatment across the VHA. This study furthered this objective by
identifying characteristics associated with benzodiazepine prescribing. Findings
suggest that interventions could be designed to target individual high-volume
prescribers or influence prescribing culture at the facility level.
PMID- 23154835
TI - Risk for adjacent segment and same segment reoperation after surgery for lumbar
stenosis: a subgroup analysis of the Spine Patient Outcomes Research Trial
(SPORT).
AB - STUDY DESIGN: Subgroup analysis of a prospective, randomized database. SUMMARY OF
BACKGROUND DATA: Reoperation due to recurrence of index level pathology or
adjacent segment disease is a common clinical problem. Despite multiple studies
on the incidence of reoperation, there have been few comparative studies
establishing risk factors for reoperation after spinal stenosis surgery. The
hypothesis of this subgroup analysis was that lumbar fusion or particular patient
characteristics, such as obesity, would render patients with lumbar stenosis more
susceptible to reoperation at the index or adjacent levels. METHODS: The study
population combined the randomized and observational cohorts enrolled in Spine
Patient Outcomes Research Trial for treatment of spinal stenosis. The surgically
treated patients were stratified according to those who had reoperation (n = 54)
or no reoperation (n = 359). Outcome measures were assessed at baseline, 1 year,
2 years, 3 years, and 4 years. The difference in improvement between those who
had reoperation and those who did not was determined at each follow-up period.
RESULTS: Of the 413 patients who underwent surgical treatment of spinal stenosis,
54 (13%) underwent a reoperation within 4 years. At baseline, there were no
significant differences in demographic characteristics or clinical outcome scores
between reoperation and nonreoperation groups. Furthermore, between groups there
were no differences in the severity of symptoms, obesity, physical examination
signs, levels of stenosis, location of stenosis, stenosis severity, levels of
fusion, levels of laminectomy, levels decompressed, operation time, and
intraoperative or postoperative complications. There was an increased percentage
of patients with duration of symptoms greater than 12 months in the reoperation
group (56% reoperation vs. 36% no reoperation, P < 0.008). At final follow-up,
there was significantly less improvement in the outcome of the reoperation group
in MOS 36-item Short-Form Health Survey physical function (14.4 vs. 22.6, P <
0.05), Oswestry Disability Index (-12.4 vs. -21.1, P < 0.01), and Sciatica
Bothersomeness Index (-5 vs. -8.1, P < 0.006). CONCLUSION: Lumbar fusion and
instrumentation were not associated with increased rate of reoperation at index
or adjacent levels compared with nonfusion techniques. The only specific risk
factor for reoperation after treatment of spinal stenosis was duration of
pretreatment symptoms more than 12 months. The overall incidence of reoperations
for spinal stenosis surgery was 13%, and reoperations were equally distributed
between index and adjacent lumbar levels. Reoperation may be related to the
natural history of spinal degenerative disease.
PMID- 23154836
TI - Evidence for juvenile disc herniation in a homo erectus boy skeleton.
AB - STUDY DESIGN: An analysis and differential diagnosis of bony alterations in the
lower lumbar vertebrae of a Homo erectus boy skeleton. OBJECTIVE: To analyze low
back problems during early human evolution. SUMMARY OF BACKGROUND DATA: Back
problems in modern humans are often attributed to our upright, bipedal locomotion
that is thought to place huge mechanical stresses on the vertebral column.
However, little is known of this situation during the course of human evolution.
METHODS: We analyzed the lower lumbar spine of the most complete early hominid
skeleton, the 1.5-million-year-old Homo erectus boy KNM-WT 15000 from
Nariokotome, Kenya, who died at an age of approximately 8 years. We use bony
alterations as indirect evidence for disc disease in the absence of soft tissue.
RESULTS: We describe an extensive osteophytic anterior curved remodeling of the
left superior articular process of L5 and formation of a new joint at the
underside of the left pedicle of L4. This indicates collisional facet joint
subluxation, most likely as the result of juvenile traumatic disc herniation.
CONCLUSIONS: This indirect evidence of possible juvenile disc herniation in a
Homo erectus boy skeleton represents the earliest known case of this typical
human ailment that is intricately linked to upright bipedalism. The extensive
bony remodeling of the articular processes of L4 and L5 suggests that the disc
herniation occurred several months before his death. Disabling backache and
recurrent sciatica might have, at least, temporarily restricted his daily
activities, which indicates advanced social care and nursing in early Homo. We
hypothesize that the early Homo intervertebral discs were more vulnerable to
injury compared with modern humans because of a relatively small vertebral cross
sectional area.
PMID- 23154837
TI - Highly monodisperse rattle-structured nanomaterials with gold nanorod core
mesoporous silica shell as drug delivery vehicles and nanoreactors.
AB - Rattle-structured nanomaterials composed of a gold nanorod in a mesoporous silica
nanocapsule (AuNR@mSiO(2)) were prepared by a novel solution-based consecutive
process. The drug-loading properties of the nanomaterial and regrowth control of
the core nanoparticles were also studied.
PMID- 23154838
TI - Transduction of pressure signal to electrical signal upon sudden increase in
turgor pressure in Chara corallina.
AB - By taking advantage of large cell size of Chara corallina, we analyzed the
membrane depolarization induced by decreased turgor pressure (Shimmen in J Plant
Res 124:639-644, 2011). In the present study, the response to increased turgor
pressure was analyzed. When internodes were incubated in media containing 200 mM
dimethyl sulfoxide, their intracellular osmolality gradually increased and
reached a steady level after about 3 h. Upon removal of dimethyl sulfoxide,
turgor pressure quickly increased. In response to the increase in turgor
pressure, the internodes generated a transient membrane depolarization at its
nodal end. The refractory period was very long and it took about 2 h for full
recovery after the depolarizing response. Involvement of protein synthesis in
recovery from refractoriness was suggested, based on experiments using
inhibitors.
PMID- 23154839
TI - Unusual 9,19 : 24,32-dicyclotetracyclic triterpenoids from Lygodium japonicum.
AB - Lygodipenoids A (1) and B (2), two novel C33 tetracyclic triterpenoids with a new
9,19 : 24,32-dicyclopropane skeleton, were isolated from the whole grass of
Lygodium japonicum. Their structures were elucidated by spectroscopic and
chemical means. Compounds 1 and 2 were tested in transfected cultured human
embryonic kidney 293 HEK293 cells for an agonist assay, and compound 1 was
identified as a partial agonist for liver X receptor alpha.
PMID- 23154840
TI - Phytochemical analysis and cytotoxicity towards multidrug-resistant leukemia
cells of essential oils derived from Lebanese medicinal plants.
AB - Juniperus excelsa fruit essential oil as well as J. oxycedrus, Cedrus libani, and
Pinus pinea wood essential oils have been obtained with yields between 2.2 +/-
0.3 % to 3.4 +/- 0.5 % and analyzed by gas chromatography. Sesquiterpenes mainly
characterized C. libani and J. oxycedrus essential oils, while in P. pinea and J.
excelsa, monoterpenes were the most abundant compounds. In J. oxycedrus, cis
calamenene (7.8 %), cuparene (3.8 %), and cis-thujopsenal (2.0 %) have been
detected for the first time. The cytotoxic activity of these essential oils
against drug-sensitive CCRF-CEM and multidrug-resistant P-glycoprotein-expressing
CEM/ADR5000 leukemia cells has been investigated (IC50 values: 29.46 to 61.54
ug/mL). Remarkably, multidrug-resistant CEM/ADR5000 cells did not reveal cross
resistance, indicating that these essential oils might be useful to treat
otherwise drug-resistant and refractory tumors.
PMID- 23154841
TI - Neuroprotective compounds from Salix pseudo-lasiogyne twigs and their anti
amnesic effects on scopolamine-induced memory deficit in mice.
AB - Bioassay-guided fractionation of an 80% methanolic extract of Salix pseudo
lasiogyne twigs has resulted in the isolation of two new compounds (1-2) along
with ten known ones (3-12). The new compounds were determined to be 3'-O
acetylsalicin (1) and 2',6'-O-acetylsalicortin (2) by using spectroscopic
analyses. Compounds (3-12) were identified as salicin (3), 2'-O-acetylsalicin
(4), salicortin (5), 2'-O-acetylsalicortin (6), 3'-O-acetylsalicortin (7), 6'-O
acetylsalicortin (8), 2'-O-(E)-rho-coumaroylsalicortin (9), grandidentatin (10),
isograndidentatin (11), and saligenin (12). Among the isolated compounds,
compounds 2, 5, 6, 7, and 8 bearing 1-hydroxy-6-oxo-2-cyclohexenecarboxylate
moiety significantly inhibited lipopolysaccharide-induced nitric oxide production
in BV2 microglial cells in vitro. Further, we studied anti-amnesic activities of
the 80% methanolic extract, the EtOAc fraction, and compound 6 from S. pseudo
lasiogyne. They exerted a significant cognitive-enhancing effect on scopolamine
induced memory deficit in mice. In addition, they also significantly increased
the reduced activities of glutathione reductase and superoxide dismutase and the
glutathione content in the hippocampus and cortex of scopolamine-induced amnesic
mice.
PMID- 23154843
TI - Phenylpropanoid-substituted procyanidins and tentatively identified procyanidin
glycosides from hawthorn (Crataegus spp.).
AB - The rational use of hawthorn leafs and flowers from Crataegus spp. for declining
cardiac performance is mainly due to flavon-C-glycosides and oligomeric
procyanidins (OPC). From OPC-enriched extracts from different batches, a dimeric
phenylpropanoid-substituted procyanidin (cinchonain II b, 1) was isolated and
characterized by MS, CD, and NMR. Also the presence of higher oligomeric
cinchonains (degree of polymerization 3 to 8) in hawthorn extracts was shown by a
specific ultrahigh-pressure liquid chromatography-ESI-qTOF-MS method.
Interestingly, strong evidence for the occurrence of oligomeric procyanidin
hexosides was found by ultrahigh-pressure liquid chromatography-ESI-qTOF-MS
analysis which additionally revealed the presence of peaks indicative of dimeric
procyanidin hexosides by their exact mass, which were clearly distinguishable
from the cinchonain II type peaks.
PMID- 23154842
TI - Suppression of melanin synthesis by the phenolic constituents of sappanwood
(Caesalpinia sappan).
AB - Sappanwood (Caesalpinia sappan Linn.) is used as an herbal medicine. It is
sometimes used to treat skin damage or as a facial cleanser. In the present
study, the methanol (MeOH) extract of sappanwood was found to inhibit melanin
synthesis in cultured human melanoma HMV-II cells stimulated with forskolin, and
six active compounds (1-5 and 7) were isolated from the extract along with a non
active compound (6). Compounds 2-7 were identified as sappanchalcone (2), 3'
deoxy-4-O-methylsappanol (3), brazilein, (4), brazilin (5), sappanol (6), and 4-O
methylsappanol (7). Compound 1 was a new compound, and its structure was
determined to be (6aS,11bR)-7,11b-dihydro-6H-indeno[2,1-c]chromene-3,6a,10,11
tetrol by spectroscopic analyses. Among the six active compounds, brazilin (5)
(EC50: 3.0 +/- 0.5 uM) and 4-O-methylsappanol (7) (EC50: 4.6 +/- 0.7 uM) strongly
suppressed melanin synthesis in HMV-II cells. Bioactive compounds showed moderate
cytotoxicities against HMV-II cells with IC50 values of 83.1 +/- 4.0 uM (for 2),
72.0 uM +/- 2.4 (for 3), 33.8 +/- 1.1 uM (for 4), 18.4 +/- 0.8 uM (for 5), and
20.2 +/- 0.8 (for 7), respectively. Brazilin (5) selectively suppressed the
expression of mRNAs for tyrosinase-related protein (TYRP) 2 and tyrosinase but
did not influence the expression of TYRP1. These results suggest that brazilin
(5) is a new class of melanin inhibitor and that sappanwood could be used as a
cosmetic material.
PMID- 23154844
TI - Validation of a novel algorithm for quantification of the percentage of signal
fractionation in atrial fibrillation.
AB - AIMS: Catheter ablation for paroxysmal atrial fibrillation (AF) is rapidly
becoming a standard practice. There is literature to support that catheter
ablation of persistent AF requires additional 'substrate modification'. In
clinical practice, operators rely on automated fractionation maps created by
three-dimensional anatomic mapping systems to rapidly assess complex
'fractionated' signals (CFAE). These systems use differing algorithms to automate
the process. The agreement between operators and contemporary algorithms has not
been examined. We sought to assess the agreement between operators and a novel
method of quantification calculating percentage fractionation (PF). METHODS AND
RESULTS: Expert opinion on 80 atrial electrogram 4 s signals of varying levels of
activity were gathered and pooled for comparison. Twelve independent experts
visually quantified the signal fractionation and offered a threshold level for
ablation. We developed an algorithm to find sites with high continuous electrical
activity, or high PF. Correlation between experts and PF was 0.78 [P < 0.01, 95%
confidence interval (CI) (0.68-0.86)]. Receiver operating characteristics curve
sensitivity and specificity for PF were 0.7727 and 0.8103 at the optimal cut-off
point of 58.45 PF with area under curve 0.89 CI (0.80-0.99). CONCLUSION: The PF
statistic represents a more robust and intuitive measure to represent
fractionated atrial activity; importantly it demonstrates excellent agreement
with expert users and presents a new standard for algorithm assessment. Use of a
PF statistic should be considered in automated mapping systems.
PMID- 23154845
TI - [Imaging strategies for knee injuries].
AB - Injuries of the knees are common. The Ottawa knee rule provides decisional
support to determine whether radiographs are indicated or not. With the use of
ultrasound it is possible to detect defects of the extensor ligaments and the
anterior cruciate ligament. Furthermore, it is possible to detect indirect signs
of an intra-articular fracture, e.g. lipohemarthrosis. In complex fractures, e.g.
tibial plateau fractures, further diagnostic procedures with multislice computed
tomography (CT) are needed for accurate classification and preoperative planning.
Multislice CT with CT angiography enables three-dimensional reconstruction of the
knee and non-invasive vascular imaging for detection of vascular injury. Magnetic
resonance imaging (MRI) is the gold standard for detection of occult fractures
and injuries of the ligaments and menisci. Higher field strengths can be used to
improve the diagnostics of cartilage lesions. Virtual MR arthrography is superior
to conventional MRI for detection of cartilage lesions especially after meniscus
surgery.
PMID- 23154846
TI - [Radiological findings, evaluation and treatment of patellofemoral pain after
total knee arthroplasty].
AB - Total knee arthroplasty (TKA) is one of the most successful operative procedures
over the last decades in orthopedic surgery; however, some patients suffer from
pain, limited range of motion, instability, infections or other complications
postoperatively. Patellofemoral pain (PFP) in particular is a common problem
after TKA and often necessitates revision surgery. Mainly increasing and
localized contact pressure and patella maltracking are held responsible for PFP
but the reasons vary. Diagnostics and therapy of PFP is not easy to manage and
should be treated following a clinical pathway. The authors suggest that patients
with PFP should be categorized after basic diagnostic measures according to the
suspected diagnosis: (1) tendinosis, (2) mechanical reasons, (3) intra-articular
non-mechanical reasons and (4) neurogenic/psychiatric reasons. Efficient
application of special diagnostic measures and further therapy is facilitated by
this classification.
PMID- 23154847
TI - [Imaging of postarthroscopic complications after knee injuries].
AB - The most common joint injuries in professional and recreational sports
participants and also in the total population are knee injuries. Arthroscopy is
indicated if this modality will improve the patient outcome and potential long
term complications can be avoided. Although uncommon, complications following
arthroscopy are mostly evaluated by magnetic resonance imaging (MRI). For
planning further therapy strategies following postarthroscopic complications,
e.g. if anterior cruciate ligament (ACL) reconstruction is required, digital
radiographs and computed tomography (CT) are helpful. This article provides an
overview of the different procedures for surgical treatment which are a
prerequisite for the analysis of postarthroscopic images. In addition typical
complications after treatment of meniscal and chondral injuries as well as after
ACL reconstruction are described and typical signs in MRI, radiography and CT are
explained in detail.
PMID- 23154848
TI - [Femoral osteonecrosis - Ahlbaeck's disease].
AB - Osteonecrosis of the knee can present as a spontaneous, primary (SPON) or a
secondary clinical entity (SON). The natural history of SPON follows a course of
several sequential stages which seem to be irreversible in later stages of both
entities. Early diagnosis of ON is crucial and the earlier the stage of the
lesion at the time of diagnosis, the better the prognosis. Clinically, early
diagnosis and treatment of ON might prevent unnecessary surgery in cases with a
concomitant degenerative meniscal tear. From a medicolegal viewpoint early-stage
ON should be ruled out prior to surgery as arthroscopy has recently been
associated with ON. Recent biopsy studies showed that SPONK is most likely caused
by insufficiency fractures which seem to appear as osteonecrotic lesions in later
stages of the disease due to failed bone healing.
PMID- 23154849
TI - [Tumor-like diseases of the knee joint].
AB - CLINICAL/METHODICAL ISSUE: Radiological diagnostics of tumor-like lesions of the
knee joint. STANDARD RADIOLOGICAL METHODS: Magnetic resonance imaging (MRI),
computed tomography (CT) and X-ray imaging. PERFORMANCE: Up to now there have
been no studies regarding sensitivity and specificity of the various diagnostic
tools (MRI, CT, X-ray) for the visualization of soft tissue tumors of the knee.
PRACTICAL RECOMMENDATIONS: The method of first choice for detecting soft tissue
tumors and tumor-like lesions in the knee joint is MRI.
PMID- 23154850
TI - [Tumors and pseudotumors of the mediastinum].
AB - Space occupying lesions of the mediastinum are relatively common. They represent
a wide spectrum of diseases including highly malignant tumors requiring immediate
further diagnostic and therapeutic procedures as well as clinically insignificant
findings and normal variants. This review provides an overview of different
mediastinal tumors and pseudotumors. Furthermore, it aims at enabling the reader
to classify mediastinal lesions according to the pathogenesis and clinical
significance. Localization of the lesion within a specific mediastinal
compartment may suggest the etiology and thus the differential diagnosis. Also,
morphological imaging criteria may suggest the diagnosis. The reader of this
review should be able to reliably classify mediastinal lesions which exhibit
these specific features without histological examination.
PMID- 23154852
TI - A CURVICYLINDRICAL COORDINATE SYSTEM FOR THE VISUALIZATION AND SEGMENTATION OF
THE ASCIDIAN TAIL.
AB - State of the art biological imaging methods, such as confocal microscopy, create
3D volumes by sampling on a cartesian grid. This cartesian coordinate system is
often not convenient for visualization and analysis of multi layered organs or
tissues. The ascidian embryonic tail, for example, is organized along
anterioposterior (AP), dorsoventral (DV) and left-right (LR) axes that are
locally orthogonal but curved in the XYZ microscope space. Here, we propose a
"curvicylindrical" coordinate system for analysis of such biological structures.
By extracting representative paths that traverse different tissue layers, the
embryo can be visualized in a small number of 2D images (3 images in the case of
the ascidian tail). As we demonstrate, this reduction of the dimensionality from
3D to 2D facilitates the initialization process for high quality segmentation of
different cell types, and identification of tissue boundaries.
PMID- 23154853
TI - Unravelling homeostatic interactions in inhibitory and excitatory networks in
human motor cortex.
PMID- 23154854
TI - Of apples and oranges: GABA and glutamate transmission in neurones of the nucleus
tractus solitarii could not be more different.
PMID- 23154855
TI - The elusive roles of NMDA receptor amino-terminal domains.
PMID- 23154856
TI - [Stage diving - a dangerous "sport"].
PMID- 23154857
TI - An endovascular technique for treatment of high-risk iatrogenic aortic
pseudoaneurysms with the ethylene vinyl alcohol copolymer onyx and aortic stent
grafting.
PMID- 23154858
TI - [Intrapancreatic accessory spleen - an important differential diagnosis of
primary pancreatic tail neoplasia].
PMID- 23154859
TI - [Interventional treatment of splenic vein thrombosis and esophageal varices
hemorrhage].
PMID- 23154860
TI - [A rare but serious radiological diagnosis view - emphysematous pyelonephritis].
PMID- 23154861
TI - [Ipilimumab-induced hypophysitis].
PMID- 23154862
TI - [Dose area product of pediatric VCUG with regard to the strongly lowered German
diagnostic reference levels].
AB - PURPOSE: To compare the dose area products of pediatric VCUG in daily practice
with the dramatically reduced official German diagnostic reference levels, which
are based on selected data. MATERIALS AND METHODS: 413 consecutive pediatric VCUG
examinations were analyzed. RESULTS: The mean dose area product of all
examinations was 0.97 dGycm2. This is below the lowest reference level that is
valid for neonates. In 12 cases (5.6 %) the achieved dose area product was higher
than the corresponding reference level. CONCLUSION: Using the available
techniques for radiation protection, it is possible in the daily routine to meet
the official diagnostic reference levels for children, which have been reduced by
up to 80 %, even though these levels are based on a selected, possibly non
representative data set.
PMID- 23154863
TI - Dual nucleophilic/electrophilic capture of in situ generated iminium ethers:
towards the synthesis of functionalized amide building blocks.
AB - Rearranging its feathers: The transformation of simple linear amides into a
diverse range of branched, functionalized products by conversion to iminium
esters is followed by sequential treatment with nucleophiles and electrophiles
(see scheme). The method takes advantage of a novel Claisen rearrangement and the
use of aromatic substrates greatly facilitates the formation of the intermediate
iminium ether.
PMID- 23154864
TI - Quality of life of oropharyngeal cancer patients with respect to treatment
strategy and p16-positivity.
AB - OBJECTIVES/HYPOTHESIS: To assess the quality of life in long-term survivors with
oropharyngeal cancer (OPSCC), compare the results with our historic cohort in
relation to the radiation technique, and explore the influence of treatment
strategy and p16 expression on quality of life (QoL). STUDY DESIGN: Retrospective
chart analysis and patient response to EORTC QLQ-C30 and EORTC QLQ-H&N35 survey
questionnaires. METHODS: 98/120 (82%) survivors treated by primary intensity
modulated chemoradiation (n = 55), or surgery with (n = 30) or without (n = 13)
adjuvant radiotherapy (RT), completed and returned the questionnaires. RESULTS:
Surgically treated patients complained about significantly less troubles with dry
mouth and teeth compared to the nonsurgically treated group. Comparing patients
treated with surgery alone and those receiving any kind of RT (primary or
adjuvant) the latter group complained about significantly more problems. Patients
with p16-positive tumors demonstrated significantly higher tumor stages, but
significantly better scores in physical and role functions. CONCLUSIONS: Early
disease can be treated with high long-term QoL by surgery alone. Primary surgery
with postoperative RT in selected patients with limited primary tumors and
advanced neck disease renders excellent QoL. Our results suggest that IMRT is
superior to former radiation techniques with regard to QoL, and should be
considered as standard of care in patients undergoing RT for OPSCC. Patients with
p16 positive tumors appear to show not only a better outcome but also report on a
better QoL.
PMID- 23154865
TI - Enhanced heterodimerization of Bax by Bcl-2 mutants improves irradiated cell
survival.
AB - B Cell Lymphoma-2 (Bcl-2) protein suppresses ionizing radiation-induced apoptosis
in hemato-lymphoid system. To enhance the survival of irradiated cells, we have
compared the effects and mechanism of Bcl-2 and its functional variants, D34A
(caspase-3 resistant) and S70E (mimics phosphorylation on S70). Bcl-2 and its
mutants were transfected into hematopoietic cell line and assessed for cell
survival, clonogenicity and cell cycle perturbations upon exposure to ionizing
radiation. The electrostatic potential of BH3 cleft of Bcl-2/mutants and their
heterodimerization with Bcl-2 associated X protein (Bax) were computationally
evaluated. Correspondingly, these results were verified by co-immunoprecipitation
and western blotting. The mutants afford higher radioprotective effect than Bcl-2
in apoptotic and clonogenic assays at D(0) (radiation dose at which 37 % cell
survival was observed). The computational and functional analysis indicates that
mutants have higher propensity to neutralize Bax protein by heterodimerization
and have increased caspase-9 suppression capability, which is responsible for
enhanced survival. This study implies potential of Bcl-2 mutants or their
chemical/peptide mimics to elicit radioprotective effect in cells exposed to
radiation.
PMID- 23154866
TI - Molecular basis of primary iron overload in India and the role of serum-derived
factors in hepcidin regulation.
PMID- 23154867
TI - Relapse of aHUS after discontinuation of therapy with eculizumab in a patient
with aHUS and factor H mutation.
PMID- 23154868
TI - Prenatal diagnosis of ambient cistern cyst.
PMID- 23154869
TI - Strain assessment in surgically resected inflammatory and neoplastic bowel
lesions.
AB - PURPOSE: To investigate whether ultrasound-based strain imaging can discriminate
between colorectal adenocarcinomas and stenotic Crohn's lesions in newly resected
surgical specimens. MATERIALS AND METHODS: Resected surgical specimens from 27
patients electively operated for colorectal tumors or stenotic lesions from
Crohn's disease were prospectively examined with ultrasonography using a Hitachi
HV 900 US scanner with real-time elastography (RTE). Three different methods were
applied to assess tissue strain: A four-level categorical visual classification,
a continuous visual analog scale (VAS, 0 - 100) and a strain ratio (SR)
measurement between the lesion and surrounding reference tissue. The imaged
sections were marked and subsequently examined by a pathologist. Results from RTE
were evaluated according to diagnosis, degree of fibrosis, inflammatory
parameters, tumor stage and grade. RESULTS: 16 sections from Crohn's lesions, 18
sections from adenocarcinomas and 4 sections from adenomas were examined. Both
adenocarcinomas and Crohn's lesions were found to be harder than the surrounding
tissue, but they could not be discriminated from each other by any of the strain
imaging evaluation methods. All adenocarcinomas had significantly higher strain
ratios than adenomas. The categorical classification differentiated poorly
between Crohn's lesions, adenocarcinomas and adenomas. Categorical evaluation and
VAS score showed fair interobserver agreement. SR measurements provided semi
quantitative strain data and added improved information about elasticity
properties, despite substantial intra-observer variation. CONCLUSION:
Sonoelastography with SR measurements and visual evaluation of strain differences
could not differentiate stenotic Crohn's lesions from adenocarcinomas in resected
bowel specimens. A small number of adenomas were found to be significantly softer
than adenocarcinomas using the same evaluation methods. The tumor stage or grade
did not have a significant impact on the elastography results.
PMID- 23154870
TI - Imaging features of intrahepatic biliary cystadenoma and cystadenocarcinoma on B
mode and contrast-enhanced ultrasound.
AB - PURPOSE: To investigate the imaging features of intrahepatic biliary cystadenoma
and cystadenocarcinoma on B-mode and contrast-enhanced ultrasound. MATERIALS AND
METHODS: The B-mode and contrast-enhanced ultrasound features of 6 intrahepatic
biliary cystadenomas and 7 intrahepatic biliary cystadenocarcinomas were
retrospectively analyzed, and the differences between cystadenomas and
cystadenocarcinomas were compared. RESULTS: There were no significant differences
between cystadenomas and cystadenocarcinomas in terms of patient gender, age,
lesion location, size, and shape (all p > 0.05). On conventional ultrasound,
biliary cystadenomas were more likely to be multilocular (6/6 for cystadenoma vs.
2/7 for cystadenocarcinoma) and cystadenocarcinomas more likely presented the
features of a mural or septal nodule and a nodule diameter > 1.0 cm (0/6 for
cystadenoma vs. 5/7 for cystadenocarcinoma). On contrast-enhanced ultrasound,
hyper-enhancement (n = 4) or iso-enhancement (n = 2) was present in the cystic
wall, septations or mural nodules of the cystadenomas during the arterial phase
and the enhancement washed out to hypo-enhancement (n = 6) during the late phase.
Cystadenocarcinomas also showed hyper-enhancement (n = 4) or iso-enhancement (n =
3) in the cystic wall, septations or mural nodules during the arterial phase and
iso-enhancement (n = 1) or hypo-enhancement (n = 6) during the late phase.
CONCLUSION: Intrahepatic biliary cystadenomas are more typically multilocular
cystic lesions. A mural or septal nodule and a nodule diameter greater than 1.0
cm on conventional ultrasound are suggestive of cystadenocarcinomas. Contrast
enhanced ultrasound is helpful for depicting the vascularity of the lesions but
there was no significant difference between cystadenomas and cystadenocarcinomas.
PMID- 23154871
TI - Dynamic contrast-enhanced ultrasound (DCE-US) for easy and rapid evaluation of
hepatocellular carcinoma compared to dynamic contrast-enhanced computed
tomography (DCE-CT)--a pilot study.
AB - PURPOSE: To check the feasibility of the easy quantification of tumor
vascularization derived from dynamic contrast-enhanced ultrasound (DCE-US) in
comparison to dynamic contrast-enhanced computed tomography (DCE-CT) in patients
with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: 19 patients with
cirrhosis and histologically proven HCC prospectively underwent CEUS (SonoVue)
and CT (Imeron400). Following CEUS, the software ImageJ was used for the easy
quantification of the echogenicity in HCC lesions and tumor-free liver
parenchyma. For DCE-CT we used the software Hepacare and created arterial
enhancement fraction color maps of the whole liver and HCC lesions. RESULTS:
Unifocal/multifocal HCCs were detected in 12/7 (US) and 10/9 patients (CT) and
biopsied nodules were defined as a reference lesion with a median of 40 mm (US)
and 42 mm (CT). CEUS showed HCC-typical hyper-/hypoenhancement in the
arterial/late phase in 16/19 reference lesions, while all reference lesions
showed an HCC-typical vascular pattern in CT. With DCE-US, quantitative
assessment could not be performed in 3/19 patients due to respiratory motion or
insufficient image quality. 13/16 reference lesions showed an HCC-typical
vascular pattern. Quantitative assessment was possible with DCE-CT in all
patients and all reference nodules showed HCC-typical values of the arterial
enhancement fraction. There was no statistical difference between CEUS, DCE-US
and DCE-CT in the quantitative assessment of contrast enhancement. CONCLUSION:
The quantitative evaluation of DCE-US was feasible in HCC without a statistical
difference with respect to DCE-CT. Further studies with a larger study population
including small nodules <= 2 cm are needed to assess whether this technique is
helpful in routine ultrasound.
PMID- 23154872
TI - Protein surface and core dynamics show concerted hydration-dependent activation.
AB - By specifically labeling leucine/valine methyl groups and lysine side chains
"inside" and "outside" dynamics of proteins on the nanosecond timescale are
compared using neutron scattering. Surprisingly, both groups display similar
dynamics as a function of temperature, and the buried hydrophobic core is
sensitive to hydration and undergoes a dynamical transition.
PMID- 23154873
TI - Clinical impact of A/H1/N1/09 influenza in patients with cirrhosis: experience
from a nosocomial cluster of infection.
AB - A/H1N1/09 influenza is associated with a high risk of complications in patients
with chronic diseases, but data on morbidity and mortality in patients with
cirrhosis are limited. A cluster of A/H1N1/09 infection in 48 patients admitted
to a Gastro-Hepatology Unit is reported. Nosocomial spread, clinical outcome, and
viral characteristics of A/H1N1/09 strains from a study group of 48 inpatients
(21 and 27 with and without cirrhosis, respectively) were compared with those
from a control group of 44 outpatients with mild influenza-like illness and
without cirrhosis. A/H1N1/09 infection was confirmed in 8/48 (17%) inpatients.
A/H1N1/09 infection rate did not differ in patients with and without cirrhosis
(4/21, 19%; 4/27, 15%), but three patients with cirrhosis died of pneumonia and
acute respiratory distress syndrome, with fungal or bacterial superinfection in
two cases, despite antiviral treatment. None of patients without cirrhosis died.
Viral sequences showed the presence of hemagglutinin mutation D222G in two out of
three fatal cases and S183P in seven out of eight infected patients. These
mutants were not detected in the outpatients group. Even if A/H1N1/09 infection
rate in hospitalized patients with and without cirrhosis was not significantly
different, cirrhosis and D222G/S183P substitutions were significantly associated
with severe disease and poor outcome, also suggesting fungal or bacterial
superinfection and portal hypertension as risk factors for A/H1N1/09 disease
severity in patients with cirrhosis. Vaccination, preventive and early treatment
and a strict control of nosocomial spread should be activated carefully in
patients with cirrhosis during epidemics influenza.
PMID- 23154874
TI - Should lamivudine monotherapy be stopped or continued in patients infected with
hepatitis B with favorable responses after more than 5 years of treatment?
AB - Regarding the limited evidence for determining the optimal duration of antiviral
treatment for hepatitis B, the long-term outcome of patients with favorable
responses to over 5 years of lamivudine monotherapy was investigated. Two hundred
seventy-one patients who had received lamivudine for at least 5 years were
enrolled. Ultimately, 72 patients without YMDD mutations and showing hepatitis B
virus (HBV) DNA levels <2.5 pg/ml after 5 years of treatment were analyzed. Mean
treatment duration with lamivudine was 9.1 +/- 2.6 years. During the treatment,
HBeAg and HBsAg loss/seroconversion rates were 95 and 6.9%, respectively.
Decompensation and hepatocellular carcinoma (HCC) developed in 2.8 and 6.9% of
patients, respectively. Old age and cirrhosis were risk factors for HCC
development. Finally, 11.1% of patients developed YMDD mutations after 8.3 +/-
2.4 years of treatment. There was no hepatic decompensation among the patients
who developed delayed YMDD mutations. Sixteen patients who achieved a complete
response stopped lamivudine and four patients showed relapses 10.3 +/- 8.5 months
after stopping lamivudine. Relapsed patients had more cirrhotic livers and higher
rates of HBeAg positivity at 5 years than patients who maintained complete
response. The present study suggests that patients who do not develop YMDD
mutations over 5 years of treatment with lamivudine may continue lamivudine
monotherapy until the loss of HBsAg. However, even for the patients showing
favorable response over 5 years of treatment, those in older ages, with cirrhosis
or who show poor HBeAg responses should be on careful monitoring to detect the
development of viral mutations, relapse and even HCC.
PMID- 23154875
TI - Molecular analysis of hepatitis B virus in Bulgaria.
AB - Hepatitis B virus infection is a global health problem. Based on the sequence
divergence of the entire genome, hepatitis B virus has been classified into eight
genotypes which have a characteristic geographic distribution. To date, no data
are available on the molecular epidemiology of hepatitis B virus in Bulgaria. The
aim of the present study was to reconstruct the epidemiological history of HBV
genotypes/subgenotypes circulating in Bulgaria using a phylodynamic approach and
a Bayesian statistical inference framework. Sequence analysis of the
HBsAg/Reverse Transcriptase overlapping genomic regions revealed that D1 and A2
were the subgenotypes detected most frequently in the patients examined. The
tMRCA estimations of the few HBV D1 Bulgarian significant clades dated back to 23
27 years ago, corresponding to the early 1980s. The HBV A2 Bulgarian sequences
fell into two closely related supported clusters dated to 2003 and 1996 years,
respectively, suggesting a more recent introduction of subgenotype A2 into
Bulgaria. The study provides new information about the HBV subgenotypes in
Bulgaria.
PMID- 23154876
TI - Baseline factors and early viral response (week 4) to antiviral therapy with
peginterferon and ribavirin for predicting sustained virologic response in
patients infected with hepatitis C virus genotype 1: a multicenter study.
AB - Both baseline predictive factors and viral response at week 4 of therapy are
reported to have high predictive ability for sustained virologic response to
peginterferon and ribavirin combination therapy in patients with hepatitis C
virus (HCV) genotype 1. However, it is not clear how these baseline variables and
week 4 response should be combined to predict sustained virologic response. In
this multicenter study, the authors investigated the impact of baseline
predictive factors on the predictive value of week 4 viral response. Receiver
operating characteristic curve analyses were performed to evaluate the ability of
week 4 reduction in HCV RNA levels to predict sustained virologic response in 293
Japanese patients infected with HCV genotype 1b. Analyses were performed in all
patients and in patient subgroups stratified according to baseline variables.
Overall, week 4 viral reduction demonstrates a high predictive ability for
sustained virologic response. The sensitivity, specificity, positive predictive
value (PPV), negative predictive value, and accuracy were higher than those of
viral reduction at week 12. However, the best cut-off levels differ depending on
the baseline factors and they were lower in patients with unfavorable baseline
predictors. When patients had the TG/GG rs8099917 genotype, the best cut-off was
markedly low with low PPV. Week 4 viral response can be a predictor of sustained
virologic response in patients with HCV genotype 1 and is better than week 12
viral response. However, the cut-off levels should be modified based on the
baseline predictive variables.
PMID- 23154877
TI - Comparison of two commercial ELISA systems for evaluating anti-EBNA1 IgG titers.
AB - High IgG titers against the Epstein-Barr virus nuclear antigen, EBNA-1, have been
strongly correlated with the risk of developing multiple sclerosis. ELISAs are
used frequently to measure EBNA-1 titers, however concerns remain regarding the
accuracy of results. Ordering absolute results into rank quintiles for analysis
may be preferable. Using 120 serum samples, two commercially available ELISAs
(produced by DiaSorin and VirionSerion) were compared, both in terms of absolute
results and rank quintiles. The positive predictive value of the VirionSerion
ELISA was 99.1% when compared to the DiaSorin ELISA, however, the negative
predictive value was 64.3%. Sensitivity and specificity were acceptable at 95.5%
and 90.0%, respectively. There was poor correlation between absolute results,
R(2) = 0.49; and the kappa coefficient for rank quintiles was low at 0.23.
Although sensitivity and specificity appear adequate, the poor negative
predictive value and kappa coefficient are of major concern. Care must be taken
when selecting assays for experimental use.
PMID- 23154878
TI - Shedding of polyomavirus in the saliva of immunocompetent individuals.
AB - The aim of this study was to investigate and compare the frequency of BKV, JCV,
WUV, and KIV in the saliva of healthy individuals. Samples were analyzed for the
presence of polyomaviruses (BKV, JCV, WUV, and KIV) DNA by real-time PCR. Of the
291 samples tested, 71 (24.3%) were positive for at least one of the screened
polyomaviruses. Specifically, 12.7% (37/291) were positive for WUV, 7.2% (21/291)
positive for BKV, 2.4% (7/291) positive for KIV, and 0.3% (1/291) positive for
JCV. BKV and WUV co-infections were detected in 1.7% (5/291) of individuals. No
other co-infection combinations were found. The mean number of DNA copies was
high, particularly for WUV and BKV, indicating active replication of these
viruses. Polyomavirus detection was higher among individuals 15-19 years of age
(46.0%; 23/50) and >=50 years of age (33.3%; 9/27). However, the detection rate
in the first group was almost 1.7* greater than the latter. WUV infections were
more frequent in individuals between the ages of 15 and 19 years and the
incidence decreased with age. By contrast, BKV excretion peaked and persisted
during the third decade of life and KIV infections were detected more commonly in
subjects >=50 years old. These findings reinforced the previous hypotheses that
saliva may be a route for BKV transmission, and that the oral cavity could be a
site of virus replication. These data also demonstrated that JCV, WUV, and KIV
may be transmitted in a similar fashion.
PMID- 23154879
TI - Respiratory syncytial virus protects against the subsequent development of
ovalbumin-induced allergic responses by inhibiting Th2-type gammadelta T cells.
AB - Respiratory syncytial virus (RSV) infection has been hypothesized to be a risk
factor for the development of allergy and asthma, but epidemiologic studies in
humans still remain inconclusive. The association between RSV infection and
allergic diseases may be dependent on an atopic background and previous history
of RSV infection. It has been reported that RSV infection before sensitization to
an allergen decreased the production of Th2-like cytokines in the lung and the
levels of allergen-specific Th2-type antibodies in the serum. However, the
underlying mechanisms are largely unknown. In the present study, the role of
pulmonary gammadelta T cells in RSV-affected, allergen-induced airway
inflammation was investigated. BALB/c mice were sensitized to or challenged with
ovalbumin (OVA) and infected with RSV either before or after the sensitization
period. It became clear that sensitization and challenge of mice with OVA induced
a large influx of gammadelta T cells to the lungs. However, prior RSV infection
inhibited the infiltration of gammadelta T cells as well as activated gammadelta
T cells, characterized by expression of CD40L or CD69 molecular in the cell
surface. Moreover, prior RSV infection elevated the type 1 cytokine gene
expression but suppressed type 2 cytokine expression in the lung gammadelta T
cells. Adoptive transfer of gammadelta T cells from OVA-sensitized and challenged
mice increased airway inflammation, suggesting that gammadelta T cells may play a
proinflammatory role in allergic responses. These results described here support
the idea of an unknown gammadelta T cell-dependent mechanism in the regulation of
RSV-affected, allergen-induced allergic airway responses.
PMID- 23154880
TI - Molecular characterization of serotype G9 rotaviruses circulating in South Korea
between 2005 and 2010.
AB - A total of 18 rotavirus G9 strains in South Korea were collected during five
rotavirus seasons between 2005 and 2010. The relationship between these strains
was examined by analyzing the genetic variation of two major structural genes,
VP7 and VP4. All the rotavirus isolates were of the G9P[8] genotype. The VP7
phylogenetic analysis demonstrated that all of the G9 rotaviruses circulating in
South Korea belonged to lineage IIId and were within three single clusters. The
amino acid comparison of the antigenic regions of the VP7 gene suggests possible
common progenitors of these strains. Phylogenetic analysis of P[8] VP4 genotypes
indicated three lineages, P[8]-2, P[8]-3, and P[8]-4, with P[8]-3 being the most
common. The results of this study provide information on the genetic relatedness
of rotavirus G9 strains circulating in South Korea over recent years and can be
utilized for the development of effective vaccines and the identification of
reference strains for future efficacy studies.
PMID- 23154881
TI - Inhibition of Tulane virus replication in vitro with RNA interference.
AB - RNA interference (RNAi), a conserved mechanism triggered by small interfering RNA
(siRNA), has been used for suppressing gene expression through RNA degradation.
The replication of caliciviruses (CVs) with RNAi was studied using the Tulane
virus (TV) as a model. Five siRNAs targeting the non-structural, the major (VP1)
and minor (VP2) structural genes of the TV were developed and the viruses were
quantified using quantitative real time PCR (qPCR) and tissue culture infective
dose (TCID(50) ) assay. Treatment of the cells with siRNA 4 hr before viral
inoculation significantly reduced viral titer by up to 2.6 logs and dramatically
decreased viral RNA copy numbers and viral titers 48 hr post infection in four of
the five siRNAs studied. The results were confirmed by Western blot, in which the
major structural protein VP1 was markedly reduced in both the cells and the
culture medium. Two small protein bands of the shell (S) and protruding (P)
domains of the viral capsid protein were also detected in the cell lysates,
although their role in viral replication remains unknown. Since the TV shares
many biological properties with human noroviruses (NoVs), the successful
demonstration of RNAi in TV replication would provide valuable information in
control of acute gastroenteritis caused by human NoVs.
PMID- 23154882
TI - Sorafenib inhibits in vitro osteoclastogenesis by down-modulating Mcl-1.
AB - The effect of the multi-kinase inhibitor Sorafenib was investigated in an in
vitro model of human osteoclastogenesis, represented by peripheral blood
mononuclear cells (PBMCs) induced to differentiate into osteoclast-like cells in
presence of receptor activator of nuclear factor kappa B ligand (RANKL) plus
macrophage-colony stimulating factor (M-CSF). Sorafenib significantly inhibited
osteoclastic formation at clinically achievable concentrations (1-3 MUM) and
promoted autophagia with minimal induction of apoptosis. At the molecular levels,
the M-CSF + RANKL combination increased the expression level of the Bcl-2 family
member Mcl-1 protein, which is known to play a key role in the control of both
cell survival and autophagia. The simultaneous treatment with Sorafenib
significantly down-regulated endogenous Mcl-1 expression. Conversely, over
expression of Mcl-1 in primary human macrophages significantly counteracted the
anti-osteoclastic activity of Sorafenib, strongly suggesting that Mcl-1 down
regulation played a major role in mediating the inhibitory activity of Sorafenib
in cells of the osteoclastic lineage.
PMID- 23154884
TI - Placental extract protects bone marrow-derived stem/progenitor cells against
radiation injury through anti-inflammatory activity.
AB - Placental extracts have been reported to have anti-oxidative and anti
inflammatory activities. Because there is increasing evidence that ionizing
radiation induces the release of reactive oxygen species (ROS) and inflammatory
cytokines, we examined the protective effects of a placental extract against
radiation injury. C57BL/6 mice were exposed to 1 Gy of gamma-ray radiation every
day for 5 days, and placental extract (1 mg/day) was administrated orally soon
after each exposure. At 2 days after the last irradiation, mice were euthanized
to examine the numbers, colony-forming capacity, and DNA damage of
stem/progenitor cells in the peripheral blood and bone marrow. To understand the
related mechanisms, we also measured the levels of intracellular and
mitochondrial ROS, and 8-OHdG in the plasma and urine, and IL-6 and TNF-alpha in
the plasma. Compared with the placebo treatment, oral administration of placental
extract significantly increased the number and colony-forming capacity, but
decreased the DNA damage of bone marrow stem/progenitor cells. However, neither
the levels of intracellular and mitochondrial ROS in bone marrow cells, nor the
levels of 8-OHdG in the urine and plasma significantly differed between groups.
Interestingly, in comparison with the placebo treatment, placental extract
significantly decreased the levels of the inflammatory cytokines IL-6 and TNF
alpha in the plasma. Placental extract significantly attenuated the acute
radiation injury to bone marrow-derived stem/progenitor cells, and this
protection is likely to be related to the anti-inflammatory activity of the
placental extract.
PMID- 23154885
TI - Repeated administration of centhaquin to pregnant rats did not affect postnatal
development and expression of endothelin receptors in the brain, heart or kidney
of pups.
AB - The effect of repeated administration of centhaquin to pregnant rats on postnatal
development, and expression of ETA and ETB receptors was determined. Pregnant
rats were treated daily with either saline or centhaquin for 2 weeks. Male rat
pups were sacrificed on day 1, 7, 14 and 28 of birth. Brain, kidney and heart
were removed to study the expression of ETA and ETB receptor protein levels. Body
weight of pregnant rats increased steadily in both vehicle and centhaquin groups.
Expression of ETA receptors in the heart and kidney was similar in vehicle and
centhaquin treated postpartum rats, but was significantly increased in the brain
of centhaquin treated postpartum rats. No change in expression of ETB receptors
was observed. In postnatal rats, mean body weight and weights of the brain,
kidney and heart increased proportionally with advancing age and were similar in
vehicle and centhaquin groups. The expression of ETA receptors in the brain,
heart and kidneys was similar in vehicle and centhaquin groups. ETB receptor
expression significantly (p<0.001) decreased by 72% and 70% on day 28 compared to
rats of age 1, 7 and 14 days in control and centhaquin groups, respectively.
Centhaquin treated rats showed similar expression of ETA and ETB receptors
compared to vehicle treatment. This study suggests that repeated administration
of centhaquin was well tolerated by pregnant rats that gave birth to normal pups.
Centhaquin did not affect postnatal development of rats and had similar
expression of ETA and ETB receptors compared to control pups.
PMID- 23154883
TI - The nonfermentable dietary fiber hydroxypropyl methylcellulose modulates
intestinal microbiota.
AB - Diet influences host metabolism and intestinal microbiota; however, detailed
understanding of this tripartite interaction is limited. To determine whether the
nonfermentable fiber hydroxypropyl methylcellulose (HPMC) could alter the
intestinal microbiota and whether such changes correlated with metabolic
improvements, C57B/L6 mice were normalized to a high-fat diet (HFD), then either
maintained on HFD (control), or switched to HFD supplemented with 10% HPMC, or a
low-fat diet (LFD). Compared to control treatment, both LFD and HPMC reduced
weight gain (11.8 and 5.7 g, respectively), plasma cholesterol (23.1 and 19.6%),
and liver triglycerides (73.1 and 44.6%), and, as revealed by 454-pyrosequencing
of the microbial 16S rRNA gene, decreased microbial alpha-diversity and
differentially altered intestinal microbiota. Both LFD and HPMC increased
intestinal Erysipelotrichaceae (7.3- and 12.4-fold) and decreased Lachnospiraceae
(2.0- and 2.7-fold), while only HPMC increased Peptostreptococcaceae (3.4-fold)
and decreased Ruminococcaceae (2.7-fold). Specific microorganisms were directly
linked with weight change and metabolic parameters in HPMC and HFD mice, but not
in LFD mice, indicating that the intestinal microbiota may play differing roles
during the two dietary modulations. This work indicates that HPMC is a potential
prebiotic fiber that influences intestinal microbiota and improves host
metabolism.
PMID- 23154886
TI - Synthesis, biological activity and molecular modeling of 4-fluoro-N-[omega
(1,2,3,4-tetrahydroacridin-9-ylamino)-alkyl]-benzamide derivatives as
cholinesterase inhibitors.
AB - The aim of this study was to synthesize and determine the biological activity of
new derivatives of 4-fluorobenzoic acid and tetrahydroacridine towards inhibition
of cholinesterases. Compounds were synthesized in condensation reaction between 9
aminoalkyl-tetrahydroacridines and the activated 4-fluorobenzoic acid. Properties
towards inhibition of acetyl- and butyrylcholinesterase were estimated according
to Ellman's spectrophotometric method. Among synthesized compounds the most
active were compounds 4a and 4d. These compounds, in comparison with tacrine,
were characterized by the similar values of IC50. Among all obtained compounds,
4d presented the highest selectivity towards inhibition of acetylcholinesterase.
Molecular modeling studies revealed that all derivatives presented similar
extended conformation in the gorge of acetylcholinesterase, however, there were 2
main conformations in the active center of butyrylcholinesterase: bent and
extended conformation.
PMID- 23154887
TI - A validated HPLC method for the determination of eriocalyxin B in plasma and its
application to pharmacokinetic studies.
AB - The purpose of this study was to determine EriB in plasma by using the method of
HPLC and collect the preclinical pharmacokinetic parameters of EriB.The analysis
involved a simple liquid-liquid extraction. After making alkaline with NaOH,
plasma was extracted with diethyl ether and the organic extract was then
evaporated. From there, the residue was reconstituted in to the mobile phase.
Chromatographic separation was achieved on the C18 column using acetonitrile and
0.1% triethylamine as mobile phase delivered at 1.0 ml/min. The UV detector
wavelength was set at 233 nm. Standard curves were linear over the concentration
range of 50-2 500 ng/ml.The mean predicted concentrations of the quality control
(QC) samples deviated by less than 3% from the corresponding nominal values; the
intra-assay and inter-assay precision of the assay were within 10% relative
standard deviation. The extraction recovery of EriB was more than 80%.The
developed method has been applied to the pharmacokinetic study of EriB in rats.
PMID- 23154888
TI - Pharmacokinetics and potential advantages of a new oral solution of levothyroxine
vs. other available dosage forms.
AB - To better understand the pharmacokinetics and potential advantages of a
levothyroxine oral solution vs. tablets and soft gel capsules.4 randomized, 2
treatment, single-dose (600 mcg levothyroxine), 2-way crossover bioequivalence
studies in 84 healthy subjects were analyzed. Samples were collected before
dosing and until 48-72 h post-dose to calculate noncompartmental baseline
adjusted pharmacokinetic parameters: maximum concentration, time to maximum
concentration, and area-under-the-concentration-time-curve from 0 to 48 h and
from 0 to 2 h.Mean pharmacokinetic parameters (+/-standard deviation) for
tablets, capsules and solution, respectively, were: area-under-the-concentration
time-curve from 0 to 2 h (ng*h/mL)=68.4+/-32.8, 64.4+/-24.4, 99.1+/-22.7; area
under-the-concentration-time-curve from 0 to 48 h (ng*h/mL)=1 632+/-424, 1 752+/
445, 1 862+/-439; maximum concentration (ng/mL)=67.6+/-20.9, 68.0+/-15.9, 71.4+/
16.0; time of maximum concentration (hours)=2.25+/-0.99, 2.38+/-1.58, 1.96+/
1.07. Overall rate and extent of exposure were not statistically different
between formulations, but a faster onset of absorption for the solution was
suggested (greater area-under-the-concentration-time-curve from 0 to 2 h and
faster time to maximum concentration by an average of 30 min).Levothyroxine rate
and extent of exposure are similar between tested formulations. The solution
appears however to reach systemic circulation quicker as dissolution is not
needed before absorption starts. The solution's greater early exposure and a
faster time to maximal concentration of around 30 min may be of benefit to
minimize drug-food interactions and deserves further investigations.
PMID- 23154889
TI - High-voltage pyrophosphate cathode: insights into local structure and lithium
diffusion pathways.
AB - Ion-transport paths: combined modeling and neutron diffraction studies provide
atomic-scale insights into Li(2)FeP(2)O(7), a material proposed for a new lithium
battery cathode with reversible electrode operation at the highest voltage of all
known Fe-based phosphates. The results indicate that Li(+) ions are transported
rapidly through a 2D network along the paths shown in green in the picture.
PMID- 23154890
TI - Men in science.
PMID- 23154893
TI - Looping in on Ndc80 - how does a protein loop at the kinetochore control
chromosome segregation?
AB - Segregation of chromosomes during mitosis requires the interaction of dynamic
microtubules with the kinetochore, a large protein structure established on the
centromere region of sister chromatids. The core microtubule-binding activity of
the kinetochore resides in the KMN network, an outer kinetochore complex. As part
of the KMN network, the Ndc80 complex, which is composed of Ndc80, Nuf2, Spc24,
and Spc25, is able to bind directly to microtubules and has the ability to track
with depolymerizing microtubules to produce chromosome movement. The Ndc80
complex binds directly to microtubules through a calponin homology domain and an
unstructured tail in the N terminus of the Ndc80 protein. A recent flurry of
papers has highlighted the importance of an internal loop region in Ndc80 in
establishing end-on attachment to microtubules. Here I discuss these recent
findings that suggest that the Ndc80 internal loop functions as a binding site
for proteins required for kinetochore-microtubule interactions.
PMID- 23154897
TI - Comparison of Goldmann applanation and dynamic contour tonometry in a population
of Mexican open-angle glaucoma patients.
AB - To compare intraocular pressure (IOP) measurements obtained with Goldmann
applanation (GAT) and dynamic contour tonometry (DCT) in a Mexican population. 40
glaucoma patients were included in this cross-sectional observational cohort
study. IOP measurements were performed in the following order: DCT, ultrasonic
pachymetry and GAT, with a 5-minute difference between each measurement, between
8 am and 2 pm. Only DCT measurements of good quality (Q <= 3) were accepted. GAT
measurements were made three times with the same Goldmann tonometer, previously
checked for calibration errors, and the mean was used for statistical purposes.
The IOP (mean [standard deviation], 95 % confidence interval [CI]) measured with
the Goldmann tonometer (13.2 [2.4], 12.4-14.0 mmHg) was significantly lower than
that obtained with the DCT (18.4 [3.3], 17.0-19.2 mmHg), p < 0.0001. Pearson's
correlation coefficients between CCT and IOP measured with GAT and DCT were (r =
0.24, 95 % CI = 0.07-0.52, p = 0.133) and (r = 0.13, 95 % CI = -0.19 to 0.43, p =
0.412), respectively. The concordance correlation coefficient between GAT and DCT
was r c = 0.3, 95 % CI = 0.17-0.41). DCT seems to overestimate the IOP as
compared to GAT. Additionally, although there was a good correlation between the
IOP measurements assessed with either GAT or DCT, the agreement was poor.
PMID- 23154898
TI - Healthcare and the patient experience: harmonizing care and environment.
PMID- 23154899
TI - Reconsidering the semiprivate inpatient room in u.s. Hospitals.
AB - In the past 5 years, U. S. hospitals have virtually abandoned the semiprivate
inpatient room. The inconclusiveness of recent research, however, indicates that
this room type remains a potentially viable care delivery setting in both
developed and developing countries for specific patient cohorts and care
scenarios during hospitalization. Although the U.S. healthcare industry has
embraced the all-private room hospital, does the semiprivate room have a place at
all in the 21st-century American hospital? Literature on the subject, both for
and against, is summarized. This is followed by a proposal for a case study
prototype and its functional integration within a conventional medical/surgical
unit in a U.S. hospital. The results suggest that a tempered reintroduction of
semiprivatism affords opportunities for socialization, patient-family
transactions and amenities, and staff effectiveness without compromising patient
safety. Implications for environmental stewardship with respect to the carbon
neutral hospital of the 21st century are cited, as are priorities for further
evidence-based design research on this issue.
PMID- 23154900
TI - Patient-centered care: a healthcare reform imperative and a hospital design
opportunity.
PMID- 23154901
TI - The biomechanics of patient room standardization.
AB - BACKGROUND: The prevailing focus on cognitive load reduction in healthcare
environment standardization excludes a domain of healthcare delivery that could
contribute significantly to safety and efficiency through standardization, but it
has escaped discussion in the context of the biomechanics of care delivery.
Inappropriate biomechanics not only can harm caregivers but compromise care
delivery. Little, however, is known regarding the biomechanics of patient care
and the way it interacts with the configurational issues typically targeted in
healthcare environment standardization. OBJECTIVES: Examine the types of
potentially harmful or stressful actions exhibited by nurses during patient care
delivery in an acute medical/surgical setting. Examine the sources influencing
unsafe actions. METHOD: Twenty nurses provided three types of simulated care in
an experimental setting involving nine care configurations that were
systematically manipulated. A kinesiology expert coded 80 simulation segments
representing two types of task and two levels of environmental challenge to
identify potentially stressful and harmful actions. Exploratory and regression
analyses were conducted on the data. RESULTS: Analysis suggests that a
considerable proportion of potentially harmful and stressful actions are
associated with the design of the physical elements as opposed to the
configurational factors typically addressed in standardization. Both of these
factors interact to produce work-arounds that result in unsafe actions.
CONCLUSION: The standardization of healthcare environments needs a larger
framework to address both cognitive lapses and the biomechanics of care delivery.
PMID- 23154902
TI - The impact of daylight and views on ICU patients and staff.
AB - OBJECTIVE: Using a pre-test/post-test quasi-experimental study in two New
Hampshire ICUs, the impact of daylight and window views on patient pain levels,
length of stay, staff errors, absenteeism, and vacancy rates were examined. One
ICU was operational until 2007, the second opened in 2007. ICU patients were
randomly selected from cardiac surgery, pneumonia, and chronic obstructive
pulmonary disease admissions of one or more days, 58 from the old ICU, and 52
from the new. Regular medical staff members assigned to the unit between October
2006 and September 2007 (old unit) and March 2008 and February 2009 (new unit)
were included. RESULTS: Variables other than unit design had a more significant
impact on relative pain levels in each unit. Comparing light levels independent
of ICU assignment supported the hypothesis that increased light levels reduce
pain perception and length of stay, but the relationship was not statistically
significant. One trend, not statistically significant, suggested that view was
associated with reduced pain perception. A decrease in incident filings supported
the hypothesis that improved natural light and views reduced errors, but results
were not statistically significant. Some subcategories demonstrated significance.
Mean absenteeism per person decreased from 38 to 23 hours from the old unit to
the new (p = 0.05). Average vacancy rates decreased by 25% (from 10.12% to 7.49%
staff openings per year) in the old and new units (p = 0.04). CONCLUSION: High
levels of natural light and window views may positively affect staff absenteeism
and staff vacancy. Factors such as medical errors, patient pain, and length of
stay require additional research.
PMID- 23154903
TI - Impact of imaging room environment: staff job stress and satisfaction, patient
satisfaction, and willingness to recommend.
AB - BACKGROUND: The built environment significantly affects the healthcare
experiences of patients and staff. Healthcare administrators and building
designers face the opportunity and challenge of improving healthcare experience
and satisfaction through better environmental design. OBJECTIVE: The purpose of
the study was to evaluate how a novel environmental intervention for imaging
rooms, which integrated multiple elements of healing environments including
positive distractions and personal control over environment, affects the
perceptions and satisfactions of its primary users-patients and staff. METHODS:
Anonymous questionnaire surveys were conducted to compare patient and staff
perceptions of the physical environment, satisfaction, and stress in two types of
imaging rooms: imaging rooms with the intervention installed (intervention rooms)
and traditionally designed rooms without the intervention (comparison rooms).
RESULTS: Imaging technologists and patients perceived the intervention rooms to
be significantly more pleasant-looking. Patients in the intervention rooms
reported significantly higher levels of environmental control and were
significantly more willing to recommend the intervention rooms to others.
CONCLUSIONS: The environmental intervention was effective in improving certain
aspects of the imaging environment: pleasantness and environmental control.
Further improvement of the imaging environment is needed to address problematic
areas such as noise.
PMID- 23154904
TI - Wall finish selection in hospital design: a survey of facility managers.
AB - OBJECTIVE: This paper seeks to analyze healthcare facility managers' perceptions
regarding the materials used for interior wall finishes and the criteria used to
select them. It also examines differences in wall finish materials and the
selection process in three major hospital spaces: emergency, surgery, and in
patient units. These findings are compared with healthcare designers' perceptions
on similar issues, as currently documented in the literature. BACKGROUND:
Hospital design and the materials used for hospital construction have a
considerable effect on the environment and health of patients. A 2002 survey
revealed which characteristics healthcare facility designers consider when
selecting materials for healthcare facilities; however, no similar study has
examined the views of facility managers on building finish selection. METHODS: A
22-question survey questionnaire was distributed to 210 facility managers of
metropolitan, for-profit hospitals in Texas; IRB approval was obtained.
Respondents were asked to rank 10 interior wall finish materials and 11 selection
criteria for wall finishes. Data from 48 complete questionnaires were analyzed
using descriptive statistics and nonparametric statistical analysis methods.
RESULTS: The study found no statistically significant differences in terms of
wall finish materials or the characteristics for material selection in the three
major spaces studied. It identified facility managers' four most-preferred wall
finish materials and the five-most preferred characteristics, with a statistical
confidence level of greater than 95%. CONCLUSIONS: The paper underscores the
importance of incorporating all perspectives: facility designers and facility
managers should work together toward achieving common organizational goals.
PMID- 23154905
TI - Perceived neighborhood environments and leisure-time walking among korean adults:
an application of the theory of planned behavior.
AB - OBJECTIVE: To examine personal, social, and perceived environmental factors
related to leisure-time walking behavior among Korean adults using the framework
of the Theory of Planned Behavior (TPB). BACKGROUND: Sedentary lifestyle and
physical inactivity contribute to rising obesity rates and chronic diseases among
Korean adults. Understanding correlates of walking is necessary to develop
effective interventions to promote regular walking. METHODS: A cross-sectional
survey was conducted in 2008 among 424 Korean adults. Participants completed a
questionnaire on perceived neighborhood environment, the TPB constructs, and
leisure-time walking behavior. RESULTS: Those who participated in leisure-time
walking had more positive perceptions of aesthetics and expressed greater
perceived behavioral control (PBC) and intention of walking than nonwalkers.
Also, walking correlated with intention and PBC, and perceived crime safety.
Intentions were moderately to strongly associated with attitude, PBC, and
subjective norm. Integrating TPB constructs and the perceived environment
variable (crime safety) resulted in a moderate fit of the data [chi(2)= 2.372, df
= 5; p = 0.796; NFI = 0.99; RMSEA = 0.00] with approximately 45.6% variance of
intention and 19.4% of the response variance of walking explained. The model
showed that perceived safety from crime was not directly related to leisure-time
walking, but indirectly predicted walking through the TPB model. CONCLUSIONS:
Perceived safety was identified as an important environmental variable among
Korean adults, and the TPB offered a good prediction of walking behavior.
Identifying individual, social, and neighborhood environmental correlates of
walking can help develop policies to promote public health for a more active and
healthier community.
PMID- 23154906
TI - Creativity, decision making, and evidence-based design.
PMID- 23154907
TI - Generating evidence from day-to-day activities: methodological issues-part 2.
PMID- 23154908
TI - Innovations in hospital architecture.
PMID- 23154909
TI - Letter to the editors.
PMID- 23154910
TI - Switching between O- and C-glycosyltransferase through exchange of active-site
motifs.
PMID- 23154914
TI - Versatile bottom-up approach to stapled pi-conjugated helical scaffolds:
synthesis and chiroptical properties of cyclic o-phenylene ethynylene oligomers.
AB - Spring loaded: the smallest members of a family of carbon nanocoils (CNCs),
adopting a fixed helical structure, have been synthesized by introduction of one
or two staples in o-phenylene ethynylene oligomers. The chiroptical responses of
the systems having enantiopure L-tartrate-derived staples confirmed the induced
helicity. Theoretical studies suggest that these CNCs are pseudoelastic.
PMID- 23154913
TI - Effect of a synthetic link N peptide nanofiber scaffold on the matrix deposition
of aggrecan and type II collagen in rabbit notochordal cells.
AB - Self-assembling peptide nanofiber scaffolds have been studied extensively as
biological materials for 3-dimensional cell culture and repairing tissue defects
in animals. However, few studies have applied peptide nanofiber scaffolds in the
tissue engineering of intervertebral discs (IVDs). In this study, a novel
functionalized peptide scaffold was specifically designed for IVD tissue
engineering, and notochordal cells (NCs) as an alternative cell source for IVD
degeneration were selected to investigate the bioactive scaffold material. The
novel RADA16-Link N self-assembling peptide scaffold material was designed by
direct coupling to a bioactive motif link N. The link N nanofiber scaffold (LN
NS) material was obtained by mixing pure RADA16-I and RADA16-Link N (1:1)
designer peptide solutions. Although live/dead cell assays showed that LN-NS and
RADA16-I scaffold materials were both biocompatible with NCs, the LN-NS material
significantly promoted NC adhesion compared with that of the pure RADA16-I SAP
scaffold material. The depositions of aggrecan and type II collagen, which are
significant markers for IVD cells, were remarkably increased. Furthermore, the
results indicated that the link N motif, the matrix analog of the nucleus
pulposus, significantly promoted the accumulation of other extracellular matrices
in vitro. We conclude that the novel LN-NS material is a promising biological
scaffold material, and may have a broad range of applications in IVD tissue
engineering.
PMID- 23154915
TI - Bohn's nodules: an under-recognised entity.
PMID- 23154916
TI - Neurodevelopmental outcomes of extremely premature infants conceived after
assisted conception: a population based cohort study.
AB - OBJECTIVE: To compare neurodevelopmental outcomes of extremely preterm infants
conceived after assisted conception (AC) compared with infants conceived
spontaneously (non-AC). DESIGN: Population-based retrospective cohort study.
SETTING: Geographically defined area in New South Wales and the Australian
Capital Territory, Australia served by a network of 10 neonatal intensive care
units. PATIENTS: Infants <29 weeks' gestation born between 1998 and 2004.
INTERVENTION: At 2-3 years corrected age, 1473 children were assessed with either
the Griffiths Mental Developmental Scales or the Bayley Scales of Infant
Development. MAIN OUTCOME MEASURE: Moderate/severe functional disability defined
as developmental delay (Griffiths General Quotient or Bayley Mental Developmental
Index >2 SD below the mean), cerebral palsy (unable to walk without aids),
deafness (bilateral hearing aids or cochlear implant) or blindness (visual acuity
<6/60 in the better eye). RESULTS: Mortality and age at follow-up were comparable
between the AC and non-AC groups. Developmental outcome was evaluated in 217
(86.5%) AC and 1256 (71.7%) non-AC infants. Using multivariate adjusted analysis,
infants born after in-vitro fertilisation at 22-26 weeks' gestation (adjusted OR
1.79, 95% CI 1.05 to 3.05, p=0.03) but not at 27-28 weeks' gestation (adjusted OR
0.81, 95% CI 0.37 to 1.77; p=0.59) had higher rate of functional disability than
those born after spontaneous conception. CONCLUSIONS: AC is associated with
adverse neurodevelopmental outcome among high risk infants born at 22-26 weeks'
gestation. This finding warrants additional exploration.
PMID- 23154917
TI - A carborane-derivative "click" reaction under heterogeneous conditions for the
synthesis of a promising lipophilic MRI/GdBNCT agent.
AB - In this study, the Huisgen reaction has been used to functionalise a carborane
cage with a lipophilic moiety and a 1,4,7,10-tetraazacyclododecane-1,4,7,10
tetraacetic acid (DOTA) ligand to obtain a new Gd boron neutron-capture therapy
(BNCT)/magnetic resonance imaging (MRI) agent. The introduction of the triazole
units has been accomplished under both heterogeneous conditions, by the use of a
Cu-supported ionic-liquid catalyst, and homogeneous conditions. The ability of
the Gd complex of the synthesised ligand to form stable adducts with low-density
lipoproteins (LDLs) has been evaluated and then MRI has been performed on tumour
melanoma cells incubated in the presence of a Gd-complex/LDL imaging probe. It
has been concluded that the high amount of intracellular boron necessary to
perform BNCT can be reached even in the presence of a relatively low-boron
containing LDL concentration.
PMID- 23154918
TI - Cardiac output measured by uncalibrated arterial pressure waveform analysis by
recently released software version 3.02 versus thermodilution in septic shock.
AB - To evaluate the 3.02 software version of the FloTrac/VigileoTM system for
estimation of cardiac output by uncalibrated arterial pressure waveform analysis,
in septic shock. Nineteen consecutive patients in septic shock were studied.
FloTrac/VigileoTM measurements (COfv) were compared with pulmonary artery
catheter thermodilution-derived cardiac output (COtd). The mean cardiac output
was 7.7 L min(-1) and measurements correlated at r = 0.53 (P < 0.001, n = 314).
In Bland-Altman plot for repeated measurements, the bias was 1.7 L min(-1) and 95
% limits of agreement (LA) were -3.0 to 6.5 L min(-1), with a %error of 53 %. The
bias of COfv inversely related to systemic vascular resistance (SVR) (r = -0.54,
P < 0.001). Above a SVR of 700 dyn s cm(-5) (n = 74), bias was 0.3 L min(-1) and
95 % LA were -1.6 to 2.2 L min(-1) (%error 32 %). Changes between consecutive
measurements (n = 295) correlated at 0.67 (P < 0.001), with a bias of 0.1 % (95 %
limits of agreement -17.5 to 17.0 %). All changes >10 % in both COtd and COfv (n
= 46) were in the same direction. Eighty-five percent of the measurements were
within the 30 degrees -330 degrees of the polar axis. COfv with the latest
software still underestimates COtd at low SVR in septic shock. The tracking
capacities of the 3.02 software are moderate-good when clinically relevant
changes are considered.
PMID- 23154923
TI - Intrinsically copper-64-labeled organic nanoparticles as radiotracers.
AB - PET friendly: labels for PET imaging are incorporated into completely organic
porphysomes by using a fast (30 min), one-pot, high-yielding (>95 %) procedure to
produce highly stable (>48 h) radiolabeled nanoparticles that show the highest
specific activity ever reported for a (64) Cu-labeled nanoparticle. These (64) Cu
porphysomes can be accurately and noninvasively tracked in vivo.
PMID- 23154924
TI - Toward libraries of biotinylated chondroitin sulfate analogues: from synthesis to
in vivo studies.
AB - Chondroitin sulfate-E (CS-E) oligosaccharidic analogues (di to hexa) were
prepared from lactose. In these compounds, the 2-acetamido group was replaced by
a hydroxyl group. This modification speeded up the synthesis, and large
oligosaccharides were constructed in a few steps from a lactose-originated block.
The protecting groups used were as follows; Fmoc for hydroxyl groups to be
glycosylated, allyl group for anomeric position protection, and
trichoroacetimidate leaving groups were used to prepare up to octasaccharides. We
took advantage of the presence of allyl group to develop a click biotinylation,
through its transformation into a 3-azido-2-hydroxyl propyl group in two steps
(epoxidation and sodium azide epoxide opening). The biotinylating agent was a
water-soluble propargylated and biotinylated triethylene glycol (PEG). By using
surface plasmon resonance (SPR), it was shown that the di-, tetra-, and
hexasaccharides display a binding affinity and selectivity toward HSF/GSF and
CXCL12 similar to that of CS-E. A parallel study confirmed their mimicry of
natural compounds, based on the hexasaccharide interaction with Otx2, a
homeodomain protein involved in brain maturation, thus validating our
simplification approach to synthesize bioactive GAG.
PMID- 23154925
TI - Encephalopathy and liver transplantation.
AB - Liver transplantation (LT) candidates experience frequently episodic or
persistent hepatic encephalopathy. In addition, these patients can exhibit
neurological comorbidities that contribute to cognitive impairment in the pre
transplant period. Assessment of the respective contribution of hepatic
encephalopathy or comorbidities in the cognitive manifestations is critical to
estimate the neurological benefits of restoring liver function. Magnetic
resonance imaging and spectroscopy are useful to assess the impact of liver
failure or comorbidities. This assessment is critical to decide liver transplant
in difficult cases. In the early postoperative period, LT is commonly complicated
by a confusional syndrome. The possible role of persisting hepatic encephalopathy
in its development has not been clearly established. The origin is usually
considered multifactorial and relates to complications following LT, such as
infections, rejection, primary liver dysfunction, immunosuppressors, etc.... The
diagnosis and treatment is based in the recognition of comorbidities and optimal
care of metabolic disturbances. Several studies have demonstrated recovery of
cognitive function after LT in patients that have exhibited hepatic
encephalopathy. However, some deficits may persist specifically among patients
with persistent HE. Other factors present before LT that contribute to a worse
neuropsychological outcome after LT are diabetes mellitus and alcohol
consumption. Long-term after LT, cognitive function may worsen in relation to
vascular risk factors.
PMID- 23154926
TI - Dyskinesia associated with hyperglycemia and basal ganglia hyperintensity: report
of a rare diabetic complication.
AB - The syndrome of dyskinesia associated with hyperglycemia and basal ganglia
hyperintensity on T1 - weighted MR images is rare and most often affects elderly
patients with type 2 diabetes. We report a case of a 79 year-old female patient
who presented to the ED with a 12 h history of a left sided hemichoreoathetosis.
Laboratory results revealed pronounced nonketotic hyperglycemia [27 mmol/L (486
mg/dL); HbA1c 140 mmol/mol (15 %)] and brain MRI showed bilateral T1
hyperintensity in the basal ganglia, more noticeable on the right side. One week
before she had been admitted with a diagnosis of transient ischemic attack
consisting in left hemiparesthesia, also with nonketotic hyperglycemia [38.9
mmol/L (700 mg/dL)] and was discharged home with partial correction of her
metabolic disturbance. The movement disorder did not improve with adequate
glycemic control so haloperidol was started. Six weeks later she was seen on an
outpatient basis. She still had minimal residual involuntary movements of the
left arm and leg. Laboratory exams revealed a well controlled diabetes mellitus
[glycemia 6.0 mmol/L (109 mg/dL), HbA1c 57 mmol/mol (7.4 %)]. In conclusion, the
syndrome of dyskinesia associated to hyperglycemia and hyperintensity in the
basal ganglia on T1 - weighted MR images is a rare, intriguing and yet
incompletely understood complication of diabetes mellitus. The increasing number
of reported cases may help to better understand its peculiarities such as the
existence of a clear clinical radiological dissociation and to unveil
pathophysiological aspects. We suggest the possibility that the metabolic
disturbances unmask a previous established asymptomatic striatum vasculopathy.
PMID- 23154927
TI - Age-dependent deficits in fear learning in heterozygous BDNF knock-out mice.
AB - Beyond its trophic function, the neurotrophin BDNF (brain-derived neurotrophic
factor) is well known to crucially mediate synaptic plasticity and memory
formation. Whereas recent studies suggested that acute BDNF/TrkB signaling
regulates amygdala-dependent fear learning, no impairments of cued fear learning
were reported in heterozygous BDNF knock-out mice (BDNF(+/-)). Since brain BDNF
levels are known to decline with aging, we hypothesized that BDNF(+/-) mice might
show reduced fear learning at older ages. Indeed, BDNF(+/-) animals revealed an
age-dependent deficit in fear learning 3 mo after birth and beyond. Since there
were no alterations between the two genotypes during the conditioning training
and when testing short-term memory, this learning deficit most likely reflects a
deficit in memory consolidation. Importantly, there were no differences in
spontaneous motor behavior and baseline anxiety in BDNF(+/-) animals at any age
tested. Following behavioral testing quantification of BDNF levels in the
basolateral amygdala with a sensitive BDNF ELISA revealed a positive correlation
between the levels of BDNF in the amygdala and the individual learning
performance. However, the age-dependent decline in the efficiency of fear
conditioning in BDNF(+/-) mice was not accompanied by reduced BDNF expression in
the amygdala. Thus, while reduced BDNF levels in general correlate with less
efficient fear learning, this lack of BDNF can be compensated in young but not in
older animals, suggesting that the cellular mechanisms responsible for fear
learning consolidation become BDNF-dependent 3 mo after birth.
PMID- 23154929
TI - The episodic engram transformed: Time reduces retrieval-related brain activity
but correlates it with memory accuracy.
AB - We took snapshots of human brain activity with fMRI during retrieval of realistic
episodic memory over several months. Three groups of participants were scanned
during a memory test either hours, weeks, or months after viewing a documentary
movie. High recognition accuracy after hours decreased after weeks and remained
at similar levels after months. In contrast, BOLD activity in a retrieval-related
set of brain areas during correctly remembered events was similar after hours and
weeks but significantly declined after months. Despite this reduction, BOLD
activity in retrieval-related regions was positively correlated with recognition
accuracy only after months. Hippocampal engagement during retrieval remained
similar over time during recall but decreased in recognition. Our results are in
line with the hypothesis that hippocampus subserves retrieval of real-life
episodic memory long after encoding, its engagement being dependent on retrieval
demands. Furthermore, our findings suggest that over time episodic engrams are
transformed into a parsimonious form capable of supporting accurate retrieval of
the crux of events, arguably a critical goal of memory, with only minimal network
activation.
PMID- 23154928
TI - Fan-shaped body neurons are involved in period-dependent regulation of long-term
courtship memory in Drosophila.
AB - In addition to its established function in the regulation of circadian rhythms,
the Drosophila gene period (per) also plays an important role in processing long
term memory (LTM). Here, we used courtship conditioning as a learning paradigm
and revealed that (1) overexpression and knocking down of per in subsets of brain
neurons enhance and suppress LTM, respectively, and (2) suppression of synaptic
transmission during memory retrieval in the same neuronal subsets leads to
defective LTM. Further analysis strongly suggests that the brain region critical
for per-dependent LTM regulation is the fan-shaped body, which is involved in
sleep-induced enhancement of courtship LTM.
PMID- 23154930
TI - Metallo-foldamers with backbone-coordinative oxime peptides: control of secondary
structures.
AB - Metal-mediated secondary structures of peptide-based foldamers were constructed
using artificial backbone-coordinative oxime peptides. Complexation of the
peptides with Pd(II) afforded several mononuclear and dinuclear secondary
structures such as helices and hairpins as confirmed by single-crystal XRD and
NMR analyses.
PMID- 23154931
TI - Highly enantioselective intermolecular Stetter reaction of simple acrylates:
synthesis of alpha-chiral gamma-ketoesters.
AB - Simple Stetter: A novel N-heterocyclic carbene (NHC) was designed by combining an
electron-rich 2,6-dimethoxy substituent and an underestimated yet promising
chiral motif. With this NHC in hand, a highly enantioselective intermolecular
Stetter reaction of simple acrylates was developed, yielding versatile alpha
chiral gamma-ketoesters. This represents the first catalytic asymmetric route
towards these valuable compounds (see scheme).
PMID- 23154932
TI - Total structure and electronic properties of the gold nanocrystal Au36(SR)24.
AB - A golden opportunity: the total structure of a Au(36)(SR)(24) nanocluster reveals
an unexpected face-centered-cubic tetrahedral Au(28) kernel (magenta). The
protecting layer exhibits an intriguing combination of binding modes, consisting
of four regular arch-like staples and the unprecedented appearance of twelve
bridging thiolates (yellow). This unique protecting network and superatom
electronic shell structure confer extreme stability and robustness.
PMID- 23154933
TI - Adaptation of stem cells to 96-well plate assays: use of human embryonic and
mouse neural stem cells in the MTT assay.
AB - Human embryonic stem cells (hESC) are difficult to adapt to 96-well plate assays,
such as the MTT assay, because they survive best when plated as colonies, which
are not easily counted and plated accurately. Two methods were developed to
address this problem. In the first, ROCK inhibitor (ROCKi) was used, which allows
accurate counting and plating of single hESC. In the second, small colonies were
plated without ROCKi but with adaptations for accurate counting and plating. The
MTT assay was also adapted for use with mouse neural stem cells. These methods
allow the MTT assay to be conducted rapidly and accurately with high
reproducibility between replicate experiments. When screening volatile chemicals
in a 96-well plate, vapor effects may occur and dose ranges must be carefully
defined. The methods were validated using the NIH assay guidance tool. These
methodss could readily be translated to other 96-well plate assay.
PMID- 23154934
TI - Serum-free generation of multipotent mesoderm (Kdr+) progenitor cells in mouse
embryonic stem cells for functional genomics screening.
AB - This unit describes a robust protocol for producing multipotent Kdr-expressing
mesoderm progenitor cells in serum-free conditions, and for functional genomics
screening using these cells. Kdr-positive cells are able to differentiate into a
wide array of mesodermal derivatives, including vascular endothelial cells,
cardiomyocytes, hematopoietic progenitors, and smooth muscle cells. The efficient
generation of such progenitor cells is of particular interest because it permits
subsequent steps in cardiovascular development to be analyzed in detail,
including deciphering the mechanisms that direct differentiation. In addition,
the oligonucleotide transfection protocol used to functionally screen siRNA and
miRNA libraries is a powerful tool to reveal networks of genes, signaling
proteins, and miRNAs that control the diversification of cardiovascular lineages
from multipotent progenitors. Technical limitations, troubleshooting, and
potential applications of these methods are discussed.
PMID- 23154935
TI - Functional stem cell integration assessed by organotypic slice cultures.
AB - Re-formation or preservation of functional, electrically active neural networks
has been proffered as one of the goals of stem cell-mediated neural therapeutics.
A primary issue for a cell therapy approach is the formation of functional
contacts between the implanted cells and the host tissue. Therefore, it is of
fundamental interest to establish protocols that allow us to delineate a detailed
time course of grafted stem cell survival, migration, differentiation,
integration, and functional interaction with the host. One option for in vitro
studies is to examine the integration of exogenous stem cells into an existing
active neuronal network in ex vivo organotypic cultures. Organotypic cultures
leave the structural integrity essentially intact while still allowing the
microenvironment to be carefully controlled. This allows detailed studies over
time of cellular responses and cell-cell interactions, which are not readily
performed in vivo. This unit describes procedures for using organotypic slice
cultures as ex vivo model systems for studying neural stem cell and embryonic
stem cell engraftment and communication with CNS host tissue.
PMID- 23154936
TI - Genetic manipulation of human induced pluripotent stem cells.
AB - Human induced pluripotent stem cells (HIPSC) have tremendous value as a source of
autologous cells for cellular transplantation in the treatment of degenerative
diseases. The protocols described here address methods for large-scale genetic
modification of HIPSCs. The first is an optimized method for transfecting HIPSCs
cultured in feeder-free conditions. The second method allows nucleofection of
trypsinized HIPSCs at an optimal cell density. Both methods enable robust
generation of stable HIPSC transfectants within two weeks. Our protocols are
highly reproducible and do not require optimization for individual HIPSC and
human embryonic stem cell (HESC) lines.
PMID- 23154937
TI - Nitrogen-rich bis-1,2,4-triazoles-a comparative study of structural and energetic
properties.
AB - In this contribution, the synthesis and full structural and spectroscopic
characterization of five bis-1,2,4-triazoles in combination with different
energetic moieties like amino, nitro, nitrimino, azido, and dinitromethylene
groups is presented. The main goal is a comparative study on the influence of
those energetic moieties on the structural and energetic properties. A complete
characterization including IR, Raman, and multinuclear NMR spectroscopy of all
compounds is presented. Additionally, X-ray crystallographic measurements were
performed and deliver insight into structural characteristics as well as inter-
and intramolecular interactions. The standard enthalpies of formation were
calculated for all compounds at the CBS-4M level of theory, the detonation
parameters were calculated by using the EXPLO5.05 program. Additionally, the
impact as well as the friction sensitivities and the sensitivity against
electrostatic discharge were determined. The potential application of the
synthesized compounds as energetic material will be studied and evaluated by
using the experimentally obtained values for the thermal decomposition, the
sensitivity data, and the calculated performance characteristics.
PMID- 23154939
TI - Asthma exacerbations: a molecular dichotomy between antiviral and pro
inflammatory responses revealed.
PMID- 23154940
TI - Activation of canonical wnt pathway promotes differentiation of mouse bone marrow
derived MSCs into type II alveolar epithelial cells, confers resistance to
oxidative stress, and promotes their migration to injured lung tissue in vitro.
AB - The differentiation of mesenchymal stem cells (MSCs) into type II alveolar
epithelial (AT II) cells in vivo and in vitro, is critical for reepithelization
and recovery in acute lung injury (ALI), but the mechanisms responsible for
differentiation are unclear. In the present study, we investigated the role of
the canonical wnt pathway in the differentiation of mouse bone marrow-derived
MSCs (mMSCs) into AT II cells. Using a modified co-culture system with murine
lung epithelial-12 (MLE-12) cells and small airway growth media (SAGM) to
efficiently drive mMSCs differentiation, we found that GSK 3beta and beta-catenin
in the canonical wnt pathway were up-regulated during differentiation. The levels
of surfactant protein (SP) C, SPB, and SPD, the specific markers of AT II cells,
correspondingly increased in mMSCs when Wnt3a or LiCl was added to the co-culture
system to activate wnt/beta-catenin signaling. The expression of these factors
was depressed to some extent by inhibiting the pathway with the addition of DKK
1. The differentiation rate of mMSCs also depends on their abilities to
accumulate and survive in inflammatory tissue. Our results suggested that the
activation of wnt/beta-catenin signaling promoted mMSCs migration towards ALI
mouse-derived lung tissue in a Transwell assay, and ameliorated the cell death
and the reduction of Bcl-2/Bax induced by H(2) O(2), which simultaneously caused
reduced GSK 3beta and beta-catenin in mMSCs. These data supports a potential
mechanism for the differentiation of mMSCs into AT II cells involving canonical
wnt pathway activation, which may be significant to their application in ALI.
PMID- 23154938
TI - Noise-induced inner hair cell ribbon loss disturbs central arc mobilization: a
novel molecular paradigm for understanding tinnitus.
AB - Increasing evidence shows that hearing loss is a risk factor for tinnitus and
hyperacusis. Although both often coincide, a causal relationship between tinnitus
and hyperacusis has not been shown. Currently, tinnitus and hyperacusis are
assumed to be caused by elevated responsiveness in subcortical circuits. We
examined both the impact of different degrees of cochlear damage and the
influence of stress priming on tinnitus induction. We used (1) a behavioral
animal model for tinnitus designed to minimize stress, (2) ribbon synapses in
inner hair cells (IHCs) as a measure for deafferentation, (3) the integrity of
auditory brainstem responses (ABR) to detect differences in stimulus-evoked
neuronal activity, (4) the expression of the activity-regulated cytoskeletal
protein, Arc, to identify long-lasting changes in network activity within the
basolateral amygdala (BLA), hippocampal CA1, and auditory cortex (AC), and (5)
stress priming to investigate the influence of corticosteroid on trauma-induced
brain responses. We observed that IHC ribbon loss (deafferentation) leads to
tinnitus when ABR functions remain reduced and Arc is not mobilized in the
hippocampal CA1 and AC. If, however, ABR waves are functionally restored and Arc
is mobilized, tinnitus does not occur. Both central response patterns were found
to be independent of a profound threshold loss and could be shifted by the
corticosterone level at the time of trauma. We, therefore, discuss the findings
in the context of a history of stress that can trigger either an adaptive or
nonadaptive brain response following injury.
PMID- 23154941
TI - Site-specific labeling of proteins with a chemically stable, high-affinity tag
for protein study.
AB - Site-specific labeling of proteins with paramagnetic lanthanides offers unique
opportunities by virtue of NMR spectroscopy in structural biology. In particular,
these paramagnetic data, generated by the anisotropic paramagnetism including
pseudocontact shifts (PCS), residual dipolar couplings (RDC), and paramagnetic
relaxation enhancement (PRE), are highly valuable in structure determination and
mobility studies of proteins and protein-ligand complexes. Herein, we present a
new way to label proteins in a site-specific manner with a high-affinity and
chemically stable tag, 4-vinyl(pyridine-2,6-diyl)bismethylenenitrilo
tetrakis(acetic acid) (4VPyMTA), through thiol alkylation. Its performance has
been demonstrated in G47C and E64C mutants of human ubiquitin both in vitro and
in a crowded environment. In comparison with the published tags, 4VPyMTA has
several interesting features: 1) it has a very high binding affinity for
lanthanides (higher than EDTA), 2) there is no heterogeneity in complexes with
lanthanides, 3) the derivatized protein is stable and potentially applicable to
the in situ analysis of proteins.
PMID- 23154942
TI - Controlled synthesis of BiOCl hierarchical self-assemblies with highly efficient
photocatalytic properties.
PMID- 23154944
TI - Conjugate addition versus cycloaddition/condensation of nitro compounds in water:
selectivity, acid-base catalysis, and induction period.
AB - Nitroacetates and nitroacetamides react in water as in chloroform with electron
deficient dipolarophiles to give condensation or conjugate addition products
under base catalysis. In general, high selectivity towards condensation is
observed in water, with shorter induction periods than in chloroform. In water,
condensations slowly occur even without base; kinetic profiles evidence the
catalytic effect of the base, which should be related to the conversion into the
tautomer nitronic acid. Condensations in water provide convenient access to
isoxazole derivatives bearing various functional groups including ammonium,
carboxy, and carboxyamide.
PMID- 23154945
TI - I. Changes and challenges revisited.
PMID- 23154943
TI - Transient acidification and subsequent proinflammatory cytokine stimulation of
astrocytes induce distinct activation phenotypes.
AB - The foot processes of astrocytes cover over 60% of the surface of brain
microvascular endothelial cells, regulating tight junction integrity. Retraction
of astrocyte foot processes has been postulated to be a key mechanism in
pathology. Therefore, movement of an astrocyte in response to a proinflammatory
cytokine or even limited retraction of processes would result in leaky junctions
between endothelial cells. Astrocytes lie at the gateway to the CNS and are
instrumental in controlling leukocyte entry. Cultured astrocytes typically have a
polygonal morphology until stimulated. We hypothesized that cultured astrocytes
which were induced to stellate would have an activated phenotype compared with
polygonal cells. We investigated the activation of astrocytes derived from adult
macaques to the cytokine TNF-alpha under resting and stellated conditions by four
parameters: morphology, intermediate filament expression, adhesion, and cytokine
secretion. Astrocytes were stellated following transient acidification; resulting
in increased expression of GFAP and vimentin. Stellation was accompanied by
decreased adhesion that could be recovered with proinflammatory cytokine
treatment. Surprisingly, there was decreased secretion of proinflammatory
cytokines by stellated astrocytes compared with polygonal cells. These results
suggest that astrocytes are capable of multiple phenotypes depending on the
stimulus and the order stimuli are applied.
PMID- 23154946
TI - II. Lateral tilt at Caesarean section: one angle fits all or made-to-measure?
PMID- 23154947
TI - Litigation in anaesthesia: areas of high clinical risk and the National Audit
Projects.
PMID- 23154949
TI - What is an adequate measure of lung function?
PMID- 23154951
TI - Decision support system combined with automated reminders for postoperative
nausea and vomiting prophylaxis.
PMID- 23154953
TI - Goal-directed therapy: each therapeutic regimen needs its indication.
PMID- 23154955
TI - Levosimendan in a case of severe peri-myocarditis associated with influenza
A/H1N1 virus.
PMID- 23154956
TI - Do old pharmacokinetic parameter estimates predict new data?
PMID- 23154957
TI - Videolaryngoscopy allows a better view of the pharynx and larynx than classic
laryngoscopy.
PMID- 23154962
TI - The predictive validity of subjective mortality expectations: evidence from the
Health and Retirement Study.
AB - Several recent studies suggest that individual subjective survival forecasts are
powerful predictors of both mortality and behavior. Using 15 years of
longitudinal data from the Health and Retirement Study, I present an alternative
view. Across a wide range of ages, predictions of in-sample mortality rates based
on subjective forecasts are substantially less accurate than predictions based on
population life tables. Subjective forecasts also fail to capture fundamental
properties of senescence, including increases in yearly mortality rates with age.
To shed light on the mechanisms underlying these biases, I develop and estimate a
latent-factor model of how individuals form subjective forecasts. The estimates
of this model's parameters imply that these forecasts incorporate several
important sources of measurement error that arguably swamp the useful information
they convey.
PMID- 23154963
TI - Mechanism of ketone allylation with allylboronates as catalyzed by zinc
compounds: a DFT study.
AB - The mechanism of the allylation reaction between 4-chloroacetophenone and pinacol
allylboronates catalyzed by ZnEt(2) with alcohols was investigated using density
functional theory (DFT) at the M05-2X/6-311++G(d,p) level. The calculations
reveal that the reaction prefers to proceed through a double gamma-addition
stepwise reaction mechanism rather than a Lewis acid-catalyzed concerted one. The
intermediate with a four-coordinated boron center, which is formed through proton
transfer from EtOH to the ethyl group of ZnEt(2) mediated by the boron center, is
the active species and an entrance for the catalytic cycle. The latter is
composed of three elementary steps: 1) boron to zinc transmetalation leading to
the formation of allylzincate species, 2) electrophilic addition of ketone to
allylzincate species, and 3) generation of the final product with recovery of the
catalyst. The boron to zinc transmetalation step has the largest energy barrier
of 61.0 kJ mol(-1) and is predicted to be the rate-determining step. The
calculations indicate that the additive EtOH plays important roles both in
lowering the activation free energy for the formation of the four-coordinated
boron active intermediate and in transforming the low catalytic activity ZnEt(2)
into high activity zinc alkoxide species. The alcohols with a less sterically
encumbering R group might be the effective additives. The substituted groups on
the allylboronates might primarily affect the boron to zinc transmetalation, and
the allylboronates with substituents on the C(gamma) atom is poor in reactivity.
The comparison of the catalytic effect between the zinc compounds investigated
suggest that Zn(OEt)(2), Zn(OH)(2), and ZnF(2) exhibit higher catalytic
efficiency for the boron to zinc transmetalation due to the activation of the B
C(alpha) bond through orbital interactions between the p orbitals of the EtO, OH,
F groups and the empty p orbital of the boron center.
PMID- 23154964
TI - Metal-ion metathesis in metal-organic frameworks: a synthetic route to new metal
organic frameworks.
AB - A porous metal-organic framework, Mn(H(3)O)[(Mn(4)Cl)(3)(hmtt)(8)] (POST-65), was
prepared by the reaction of 5,5',10,10',15,15'-hexamethyltruxene-2,7,12
tricarboxylic acid (H(3)hmtt) with MnCl(2) under solvothermal conditions. POST
65(Mn) was subjected to post-synthetic modification with Fe, Co, Ni, and Cu
according to an ion-exchange method that resulted in the formation of three
isomorphous frameworks, POST-65(Co/Ni/Cu), as well as a new framework, POST
65(Fe). The ion-exchanged samples could not be prepared by regular solvothermal
reactions. The complete exchange of the metal ions and retention of the framework
structure were verified by inductively coupled plasma-atomic emission
spectrometry (ICP-AES), powder X-ray diffraction (PXRD), and Brunauer-Emmett
Teller (BET) surface-area analysis. Single-crystal X-ray diffractions studies
revealed a single-crystal-to-single-crystal (SCSC)-transformation nature of the
ion-exchange process. Hydrogen-sorption and magnetization measurements showed
metal-specific properties of POST-65.
PMID- 23154966
TI - New reactivity of the uranyl(VI) ion.
AB - The chemistry of the uranyl ion ([UO(2)](2+)) has evolved remarkably over the
past few years, with unexpected reactivity observed that challenge our
understanding of this ion, and of actinides in general. This review highlights
some recent advances in the field, focussing on the organometallic chemistry of
the uranyl moiety, which is not well developed in comparison to lower oxidation
states of uranium. The use of uranyl as a catalyst is highlighted and the newly
developed supramolecular chemistry is described. The uranyl oxygen atoms have
been considered as inert, but recent work has shown that is not necessarily the
case and is discussed herein. Finally, reduction to the [UO(2)](+) ion will be
discussed.
PMID- 23154965
TI - Cancer-Specific requirement for BUB1B/BUBR1 in human brain tumor isolates and
genetically transformed cells.
AB - To identify new candidate therapeutic targets for glioblastoma multiforme, we
combined functional genetics and glioblastoma network modeling to identify
kinases required for the growth of patient-derived brain tumor-initiating cells
(BTIC) but that are dispensable to proliferating human neural stem cells (NSC).
This approach yielded BUB1B/BUBR1, a critical mitotic spindle checkpoint player,
as the top-scoring glioblastoma lethal kinase. Knockdown of BUB1B inhibited
expansion of BTIC isolates, both in vitro and in vivo, without affecting
proliferation of NSCs or astrocytes. Mechanistic studies revealed that BUB1B's
GLE2p-binding sequence (GLEBS) domain activity is required to suppress lethal
kinetochore-microtubule (KT-MT) attachment defects in glioblastoma isolates and
genetically transformed cells with altered sister KT dynamics, which likely favor
KT-MT instability. These results indicate that glioblastoma tumors have an added
requirement for BUB1B to suppress lethal consequences of altered KT function and
further suggest that sister KT measurements may predict cancer-specific
sensitivity to BUB1B inhibition and perhaps other mitotic targets that affect KT
MT stability. SIGNIFICANCE: Currently, no effective therapies are available for
glioblastoma, the most frequent and aggressive brain tumor. Our results suggest
that targeting the GLEBS domain activity of BUB1B may provide a therapeutic
window for glioblastoma, as the GLEBS domain is nonessential in untransformed
cells. Moreover, the results further suggest that sister KT distances at
metaphase may predict sensitivity to anticancer therapeutics targeting KT
function.
PMID- 23154968
TI - Staphylococcus aureus protein A binding to osteoblast tumour necrosis factor
receptor 1 results in activation of nuclear factor kappa B and release of
interleukin-6 in bone infection.
AB - Staphylococcus aureus is the major pathogen among the staphylococci and the most
common cause of bone infections. These infections are mainly characterized by
bone destruction and inflammation, and are often debilitating and very difficult
to treat. Previously we demonstrated that S. aureus protein A (SpA) can bind to
osteoblasts, which results in inhibition of osteoblast proliferation and
mineralization, apoptosis, and activation of osteoclasts. In this study we used
small interfering RNA (siRNA) to demonstrate that osteoblast tumour necrosis
factor receptor-1 (TNFR-1) is responsible for the recognition of and binding to
SpA. TNFR-1 binding to SpA results in the activation of nuclear factor kappa B
(NFkappaB). In turn, NFkappaB translocates to the nucleus of the osteoblast,
which leads to release of interleukin 6 (IL-6). Silencing TNFR-1 in osteoblasts
or disruption of the spa gene in S. aureus prevented both NFkappaB activation and
IL-6 release. As well as playing a key role in proinflammatory reactions, IL-6 is
also an important osteotropic factor. Release of IL-6 from osteoblasts results in
the activation of the bone-resorbing cells, the osteoclasts. Consistent with our
results described above, both silencing TNFR-1 in osteoblasts and disruption of
spa in S. aureus prevented osteoclast activation. These studies are the first to
demonstrate the importance of the TNFR-1-SpA interaction in bone infection, and
may help explain the mechanism through which osteoclasts become overactivated,
leading to bone destruction. Anti-inflammatory drug therapy could be used either
alone or in conjunction with antibiotics to treat osteomyelitis or for
prophylaxis in high-risk patients.
PMID- 23154967
TI - bZIP transcription factors affecting secondary metabolism, sexual development and
stress responses in Aspergillus nidulans.
AB - The eukaryotic basic leucine zipper (bZIP) transcription factors play critical
roles in the organismal response to the environment. Recently, a novel YAP-like
bZIP, restorer of secondary metabolism A (RsmA), was found in a suppressor screen
of an Aspergillus nidulans secondary metabolism (SM) mutant in which
overexpression of rsmA was found to partially remediate loss of SM in Velvet
Complex mutants. The Velvet Complex is a conserved fungal transcriptional
heteromer that couples SM with sexual development in fungi. Here we characterized
and contrasted SM in mutants of RsmA and four other A. nidulans bZIP proteins
(NapA, ZipA, ZipB and ZipC) with predicted DNA binding motifs similar to RsmA.
Only two overexpression mutants exhibited both SM and sexual abnormalities that
were noteworthy: OE : : rsmA resulted in a 100-fold increase in sterigmatocystin
and a near loss of meiotic spore production. OE : : napA displayed decreased
production of sterigmatocystin, emericellin, asperthecin, shamixanthone and
epishamixanthone, coupled with a shift from sexual to asexual development.
Quantification of bZIP homodimer and heterodimer formation using fluorescence
resonance energy transfer (FRET) suggested that these proteins preferentially
self-associate.
PMID- 23154970
TI - Transcriptome changes initiated by carbon starvation in Aspergillus nidulans.
AB - Carbon starvation is a common stress for micro-organisms both in nature and in
industry. The carbon starvation stress response (CSSR) involves the regulation of
several important processes including programmed cell death and reproduction of
fungi, secondary metabolite production and extracellular hydrolase formation. To
gain insight into the physiological events of CSSR, DNA microarray analyses
supplemented with real-time RT-PCR (rRT-PCR) experiments on 99 selected genes
were performed. These data demonstrated that carbon starvation induced very
complex changes in the transcriptome. Several genes contributing to protein
synthesis were upregulated together with genes involved in the unfolded protein
stress response. The balance between biosynthesis and degradation moved towards
degradation in the case of cell wall, carbohydrate, lipid and nitrogen
metabolism, which was accompanied by the production of several hydrolytic enzymes
and the induction of macroautophagy. These processes provide the cultures with
long-term survival by liberating nutrients through degradation of the cell
constituents. The induced synthesis of secondary metabolites, antifungal enzymes
and proteins as well as bacterial cell wall-degrading enzymes demonstrated that
carbon-starving fungi should have marked effects on the micro-organisms in their
surroundings. Due to the increased production of extracellular and vacuolar
enzymes during carbon starvation, the importance of the endoplasmic reticulum
increased considerably.
PMID- 23154969
TI - Insertion mutations in Helicobacter pylori flhA reveal strain differences in RpoN
dependent gene expression.
AB - Flagellar biogenesis in the gastric pathogen Helicobacter pylori involves a
transcriptional hierarchy that utilizes all three sigma factors found in this
bacterium (RpoD, RpoN and FliA). Transcription of the RpoN-dependent genes
requires the sensor kinase FlgS and response regulator FlgR. It is thought that
FlgS senses some cellular cue to regulate transcription of the RpoN-dependent
flagellar genes, but this signal has yet to be identified. Previous studies
showed that transcription of the RpoN-dependent genes is inhibited by mutations
in flhA, which encodes a membrane-bound component of the flagellar protein export
apparatus. We found that depending on the H. pylori strain used, insertion
mutations in flhA had different effects on expression of RpoN-dependent genes.
Mutations in flhA in H. pylori strains B128 and ATCC 43504 (the type strain) were
generated by inserting a chloramphenicol resistance cassette so as to effectively
eliminate expression of the gene (DeltaflhA), or within the gene following codon
77 (designated flhA77) or codon 454 (designated flhA454), which could allow
expression of truncated FlhA proteins. All three flhA mutations severely
inhibited transcription of the RpoN-dependent genes flaB and flgE in H. pylori
B128. In contrast, levels of flaB and flgE transcripts in H. pylori ATCC 43504
bearing either flhA77 or flhA454, but not DeltaflhA, were ~60 % of wild-type
levels. The FlhA(454) variant was detected in membrane fractions prepared from H.
pylori ATCC 43504 but not H. pylori B128, which may account for the phenotypic
differences in the flhA mutations of the two strains. Taken together, these
findings suggest that only the N-terminal region of FlhA is needed for
transcription of the RpoN regulon. Interestingly, expression of an flaB'-'xylE
reporter gene in H. pylori ATCC 43504 bearing the flhA77 allele was about
eightfold higher than that of a strain with the wild-type allele, suggesting that
expression of flaB is not only regulated at the level of transcription but also
regulated post-transcriptionally.
PMID- 23154971
TI - Purification and characterization of oxygen-inducible haem catalase from oxygen
tolerant Bifidobacterium asteroides.
AB - Bifidobacterium asteroides, originally isolated from honeybee intestine, was
found to grow under 20% O(2) conditions in liquid shaking culture using MRS
broth. Catalase activity was detected only in cells that were exposed to O(2) and
grown in medium containing a haem source, and these cells showed higher viability
on exposure to H(2)O(2). Passage through multiple column chromatography steps
enabled purification of the active protein, which was identified as a homologue
of haem catalase on the basis of its N-terminal sequence. The enzyme is a
homodimer composed of a subunit with a molecular mass of 55 kDa, and the
absorption spectrum shows the typical profile of bacterial haem catalase. A gene
encoding haem catalase, which has an amino acid sequence coinciding with the N
terminal amino acid sequence of the purified protein, was found in the draft
genome sequence data of B. asteroides. Expression of the katA gene was induced in
response to O(2) exposure. The haem catalase from B. asteroides shows about 70
80% identity with those from lactobacilli and other lactic acid bacteria, and no
homologues were found in other bifidobacterial genomes.
PMID- 23154972
TI - Structural elucidation and genomic scrutiny of the C60-C100 mycolic acids of
Segniliparus rotundus.
AB - Mycolic acids, very long-chain alpha-alkyl, beta-hydroxylated fatty acids, occur
in the members of the order Corynebacteriales where their chain lengths (C(26)
C(88)) and structural features (oxygen functions, cis or trans double bonds,
cyclopropane rings and methyl branches) are genus- and species-specific. The
molecular composition and structures of the mycolic acids of two species
belonging to the genus Segniliparus were determined by a combination of modern
analytical chemical techniques, which include MS and NMR. They consist of mono
ethylenic C(62-)C(64) (alpha'), di-ethylenic C(77)-C(79) (alpha) and extremely
long-chain mycolic acids (alpha(+)) ranging from 92 to 98 carbon atoms and
containing three unsaturations, cis and/or trans double bonds and/or
cyclopropanes. The double bonds in each class of mycolic acids were positioned by
oxidative cleavage and exhibit locations similar to those of alpha- and alpha'
mycolic acids of mycobacteria. For the ultralong chain alpha-mycolic acids, the
three double bonds were located at equally spaced carbon intervals (C(13)-C(16)),
with the methyl branches adjacent to the proximal and distal trans double bonds.
Examination of the Segniliparus rotundus genome compared with those of other
members of the Corynebacteriales indicated two obvious differences in genes
encoding the elongation fatty acid (FAS-II) enzymes involved in the biosynthesis
of mycolic acids: the organization of 3-ketoacyl-ACP synthases (KasA and KasB)
and (3R)-hydroxyacyl-ACP dehydratases (HadAB/BC), on one hand, and the presence
of two copies of the hadB gene encoding the catalytic domain of the latter enzyme
type, on the other. This observation is discussed in light of the most recent
data accumulated on the biosynthesis of this hallmark of Corynebacteriales.
PMID- 23154973
TI - Transcriptional regulation of the Rhodobacter capsulatus response regulator CtrA.
AB - The Rhodobacter capsulatus response regulator CtrA controls the expression of 227
genes, some of which are upregulated by both the phosphorylated and
unphosphorylated forms of CtrA. Therefore, CtrA concentration alone, regardless
of phosphorylation state, may determine expression of downstream genes, yet
little is known about the regulation of ctrA in R. capsulatus. In this study we
used a ctrA : : lacZ fusion plasmid to study the effects of medium composition,
growth conditions and growth phase on R. capsulatus ctrA gene expression. These
experiments indicate that ctrA expression is higher when cultures are grown in
phototrophic (anaerobic) conditions compared with chemotrophic (aerobic)
conditions, and is higher when grown in a minimal medium compared with a rich
medium. We used several mutants to investigate possible regulatory pathways, and
found that in R. capsulatus ctrA is not autoregulated but is regulated by a
quorum-sensing system. The expression of ctrA increased as cell cultures moved
through exponential phase and into stationary phase, with high levels of
expression persisting long after culture turbidity plateaued. Although this
growth phase-dependent pattern of expression was also observed in a quorum
sensing mutant, the magnitude of ctrA expression was about 50% of the wild-type
strain at all phases. Furthermore, reduction of phosphate concentration in the
growth medium decreased ctrA expression in a culture density-independent manner,
whereas reduction of malic acid (carbon source) or ammonium (nitrogen source)
concentration had no effect. The regulation of ctrA expression in R. capsulatus
appears to require the coordination of multiple pathways involved in detecting a
variety of environmental conditions.
PMID- 23154974
TI - Gamma-aminobutyric acid acts as a specific virulence regulator in Pseudomonas
aeruginosa.
AB - Gamma-aminobutyric acid (GABA) is widespread in the environment and can be used
by animal and plants as a communication molecule. Pseudomonas species, in
particular fluorescent ones, synthesize GABA and express GABA-binding proteins.
In this study, we investigated the effects of GABA on the virulence of
Pseudomonas aeruginosa. While exposure to GABA (10 uM) did not modify either the
growth kinetics or the motility of the bacterium, its cytotoxicity and virulence
were strongly increased. The Caenorhabditis elegans 'fast killing test' model
revealed that GABA acts essentially through an increase in diffusible toxin(s).
GABA also modulates the biofilm formation activity and adhesion properties of
PAO1. GABA has no effect on cell surface polarity, biosurfactant secretion or on
the lipopolysaccharide structure. The production of several exo-enzymes,
pyoverdin and exotoxin A is not modified by GABA but we observed an increase in
cyanogenesis which, by itself, could explain the effect of GABA on P. aeruginosa
virulence. This mechanism appears to be regulated by quorum sensing. A proteomic
analysis revealed that the effect of GABA on cyanogenesis is correlated with a
reduction of oxygen accessibility and an over-expression of oxygen-scavenging
proteins. GABA also promotes specific changes in the expression of thermostable
and unstable elongation factors Tuf/Ts involved in the interaction of the
bacterium with the host proteins. Taken together, these results suggest that GABA
is a physiological regulator of P. aeruginosa virulence.
PMID- 23154976
TI - Independent trafficking of the KCNQ1 K+ channel and H+-K+-ATPase in gastric
parietal cells from mice.
AB - Gastric acid secretion by the H(+)-K(+)-ATPase at the apical surface of activated
parietal cells requires luminal K(+) provided by the KCNQ1/KCNE2 K(+) channel.
However, little is known about the trafficking and relative spatial distribution
of KCNQ1 and H(+)-K(+)-ATPase in resting and activated parietal cells and the
capacity of KCNQ1 to control acid secretion. Here we show that inhibition of
KCNQ1 activity quickly curtails gastric acid secretion in vivo, even when the
H(+)-K(+)-ATPase is permanently anchored in the apical membrane, demonstrating a
key role of the K(+) channel in controlling acid secretion. Three-dimensional
imaging analysis of isolated mouse gastric units revealed that the majority of
KCNQ1 resides in an intracytoplasmic, Rab11-positive compartment in resting
parietal cells, distinct from H(+)-K(+)-ATPase-enriched tubulovesicles. Upon
activation, there was a significant redistribution of H(+)-K(+)-ATPase and KCNQ1
from intracytoplasmic compartments to the apical secretory canaliculi.
Significantly, high Forster resonance energy transfer was detected between H(+)
K(+)-ATPase and KCNQ1 in activated, but not resting, parietal cells. These
findings demonstrate that H(+)-K(+)-ATPase and KCNQ1 reside in independent
intracytoplasmic membrane compartments, or membrane domains, and upon activation
of parietal cells, both membrane proteins are transported, possibly via Rab11
positive recycling endosomes, to apical membranes, where the two molecules are
closely physically opposed. In addition, these studies indicate that acid
secretion is regulated by independent trafficking of KCNQ1 and H(+)-K(+)-ATPase.
PMID- 23154975
TI - Smad7 inhibits autocrine expression of TGF-beta2 in intestinal epithelial cells
in baboon necrotizing enterocolitis.
AB - Preterm infants may be at risk of necrotizing enterocolitis (NEC) due to
deficiency of transforming growth factor-beta 2 (TGF-beta(2)) in the developing
intestine. We hypothesized that low epithelial TGF-beta(2) expression in preterm
intestine and during NEC results from diminished autocrine induction of TGF
beta(2) in these cells. Premature baboons delivered at 67% gestation were treated
per current norms for human preterm infants. NEC was diagnosed by clinical and
radiological findings. Inflammatory cytokines, TGF-beta(2), Smad7, Ski, and
strawberry notch N (SnoN)/Ski-like oncoprotein (SKIL) was measured using
quantitative reverse transcriptase-polymerase chain reaction, immunoblots, and
immunohistochemistry. Smad7 effects were examined in transfected IEC6 intestinal
epithelial cells in vitro. Findings were validated in archived human tissue
samples of NEC. NEC was recorded in seven premature baboons. Consistent with
existing human data, premature baboon intestine expressed less TGF-beta(2) than
term intestine. TGF-beta(2) expression was regulated in epithelial cells in an
autocrine fashion, which was interrupted in the premature intestine and during
NEC due to increased expression of Smad7. LPS increased Smad7 binding to the TGF
beta(2) promoter and was associated with dimethylation of the lysine H3K9, a
marker of transcriptional silencing, on the nucleosome of TGF-beta(2). Increased
Smad7 expression in preterm intestine was correlated with the deficiency of
SnoN/SKIL, a repressor of the Smad7 promoter. Smad7 inhibits autocrine expression
of TGF-beta(2) in intestinal epithelial cells in the normal premature intestine
and during NEC. Increased Smad7 expression in the developing intestine may be due
to a developmental deficiency of the SnoN/SKIL oncoprotein.
PMID- 23154977
TI - Gastrokines: stomach-specific proteins with putative homeostatic and tumor
suppressor roles.
AB - During the past decade, a new family of stomach-specific proteins has been
recognized. Known as "gastrokines" (GKNs), these secreted proteins are products
of gastric mucus-producing cell lineages. GKNs are highly conserved in physical
structure, and emerging data point to convergent functions in the modulation of
gastric mucosal homeostasis and inflammation. While GKNs are highly prevalent in
the normal stomach, frequent loss of GKN expression in gastric cancers, coupled
with established antiproliferative activity, suggests putative tumor suppressor
roles. Conversely, ectopic expression of GKNs in reparative lesions of Crohn's
disease alludes to additional activity in epithelial wound healing and/or repair.
Modes of action remain unsolved, but the recent demonstration of a GKN2-trefoil
factor 1 heterodimer implicates functional interplay with trefoil factors. This
review aims to provide a historical account of GKN biology and encapsulate the
rapidly accumulating evidence supporting roles in gastric epithelial homeostasis
and tumor suppression.
PMID- 23154978
TI - Novel 3' ends that support translation.
AB - The 3' ends of two large noncoding RNAs, MALAT1 (metastasis-associated lung
adenocarcinoma transcript 1) and MEN beta, are formed by cleavage by RNase P and
are capped but not polyadenylated. In the November 1, 2012, issue of Genes &
Development, Wilusz and colleagues (pp. 2392-2407) show that when these 3' ends
are formed on a GFP reporter, the resulting mRNA is exported to the cytoplasm and
translated. The 3' end forms a novel triple-helical structure that supports
export and translation as well as a poly(A) tail does.
PMID- 23154979
TI - Spliceosome activation: U4 is the path, stem I is the goal, and Prp8 is the
keeper. Let's cheer for the ATPase Brr2!
AB - During pre-mRNA splicing, the spliceosome is activated for catalysis by unwinding
base-paired U4/U6 small nuclear RNAs, a step that must be precisely timed. We
know that unwinding requires the ATPase Brr2, but the mechanism and regulation of
unwinding have been understood poorly. In the November 1, 2012, issue of Genes &
Development, Hahn and colleagues (pp. 2408-2421) and Mozaffari-Jovin and
colleagues (pp. 2422-2434) defined a pathway for U4/U6 unwinding. Moreover,
Mozaffari-Jovin and colleagues suggested a mechanism for regulating Brr2.
PMID- 23154980
TI - Zebrafish genetics gets the Scube on Hedgehog secretion.
AB - Inspired by a zebrafish mutation, two recent studies by Creanga and colleagues
(pp. 1312-1325) and Tukachinsky and colleagues have shed new light on the way in
which lipidated Hedgehog proteins are secreted and released from expressing
cells, suggesting a model for the sequential action of the Disp and Scube2
proteins in this process.
PMID- 23154981
TI - The SMAD2/3 corepressor SNON maintains pluripotency through selective repression
of mesendodermal genes in human ES cells.
AB - Activin/Nodal signaling via SMAD2/3 maintains human embryonic stem cell (hESC)
pluripotency by direct transcriptional regulation of NANOG or, alternatively,
induces mesoderm and definitive endoderm (DE) formation. In search of an
explanation for these contrasting effects, we focused on SNON (SKIL), a potent
SMAD2/3 corepressor that is expressed in hESCs but rapidly down-regulated upon
differentiation. We show that SNON predominantly associates with SMAD2 at the
promoters of primitive streak (PS) and early DE marker genes. Knockdown of SNON
results in premature activation of PS and DE genes and loss of hESC morphology.
In contrast, enforced SNON expression inhibits DE formation and diverts hESCs
toward an extraembryonic fate. Thus, our findings provide novel mechanistic
insight into how a single signaling pathway both regulates pluripotency and
directs lineage commitment.
PMID- 23154982
TI - Cell cycle gene-specific control of transcription has a critical role in
proliferation of primordial germ cells.
AB - Transcription elongation is stimulated by positive transcription elongation
factor b (P-TEFb), for which activity is repressed in the 7SK small nuclear
ribonucleoprotein (7SK snRNP) complex. We show here a critical role of 7SK snRNP
in growth control of primordial germ cells (PGCs). The expression of p15(INK4b),
a cyclin-dependent kinase inhibitor (CDKI) gene, in PGCs is selectively activated
by P-TEFb and its recruiting molecule, Brd4, when the amount of active P-TEFb is
increased due to reduction of the 7SK snRNP, and PGCs consequently undergo growth
arrest. These results indicate that CDKI gene-specific control of transcription
by 7SK snRNP plays a pivotal role in the maintenance of PGC proliferation.
PMID- 23154983
TI - SEL-10/Fbw7-dependent negative feedback regulation of LIN-45/Braf signaling in C.
elegans via a conserved phosphodegron.
AB - The conserved E3 ubiquitin ligase component named SEL-10 in Caenorhabditis
elegans and Fbw7 in mammals targets substrates for ubiquitin-mediated degradation
through a high-affinity binding site called a Cdc4 phosphodegron (CPD). As many
known substrates of Fbw7 are oncoproteins, the identification of new substrates
may offer insight into cancer biology as well as aspects of proteome regulation.
Here, we evaluated whether the presence of an evolutionarily conserved CPD would
be a feasible complement to proteomics-based approaches for identifying new
potential substrates. For functional assessments, we focused on LIN-45, a
component of the signal transduction pathway underlying vulval induction and the
ortholog of human Braf, an effector of Ras in numerous cancers. Our analysis
demonstrates that LIN-45 behaves as a bona fide substrate of SEL-10, with
mutation of the CPD or loss of sel-10 resulting in increased activity and protein
stability in vivo. Furthermore, during vulval induction, the downstream kinase
MPK-1/ERK is also required for LIN-45 protein degradation in a negative feedback
loop, resulting in degradation of LIN-45 where ERK is highly active. As the CPD
consensus sequence is conserved in human Braf, we propose that Fbw7 may also
regulate Braf stability in some cell contexts. We discuss the implications of our
findings for vulval development in C. elegans, the potential applicability to
human Braf, and the value of a CPD-based predictive approach for human Fbw7
substrates.
PMID- 23154984
TI - CLOCK deubiquitylation by USP8 inhibits CLK/CYC transcription in Drosophila.
AB - A conserved transcriptional feedback loop underlies animal circadian rhythms. In
Drosophila, the transcription factors CLOCK (CLK) and CYCLE (CYC) activate the
transcription of direct target genes like period (per) and timeless (tim). They
encode the proteins PER and TIM, respectively, which repress CLK/CYC activity.
Previous work indicates that repression is due to a direct PER-CLK/CYC
interaction as well as CLK/CYC phosphorylation. We describe here the role of
ubiquitin-specific protease 8 (USP8) in circadian transcriptional repression as
well as the importance of CLK ubiquitylation in CLK/CYC transcription activity.
usp8 loss of function (RNAi) or expression of a dominant-negative form of the
protein (USP8-DN) enhances CLK/CYC transcriptional activity and alters fly
locomotor activity rhythms. Clock protein and mRNA molecular oscillations are
virtually absent within circadian neurons of USP8-DN flies. Furthermore, CLK
ubiquitylation cycles robustly in wild-type flies and peaks coincident with
maximal CLK/CYC transcription. As USP8 interacts with CLK and expression of USP8
DN increases CLK ubiquitylation, the data indicate that USP8 deubiquitylates CLK,
which down-regulates CLK/CYC transcriptional activity. Taken together with the
facts that usp8 mRNA cycles and that its transcription is activated directly by
CLK/CYC, USP8, like PER and TIM, contributes to the transcriptional feedback loop
cycle that underlies circadian rhythms.
PMID- 23154985
TI - Stable intronic sequence RNA (sisRNA), a new class of noncoding RNA from the
oocyte nucleus of Xenopus tropicalis.
AB - To compare nuclear and cytoplasmic RNA from a single cell type, free of cross
contamination, we studied the oocyte of the frog Xenopus tropicalis, a giant cell
with an equally giant nucleus. We isolated RNA from manually dissected nuclei and
cytoplasm of mature oocytes and subjected it to deep sequencing. Cytoplasmic mRNA
consisted primarily of spliced exons derived from ~6700 annotated genes. Nearly
all of these genes were represented in the nucleus by intronic sequences.
However, unspliced nascent transcripts were not detected. Inhibition of
transcription or splicing for 1-2 d had little or no effect on the abundance of
nuclear intronic sequences, demonstrating that they are unusually stable. RT-PCR
analysis showed that these stable intronic sequences are transcribed from the
coding strand and that a given intron can be processed into more than one
molecule. Stable intronic sequence RNA (sisRNA) from the oocyte nucleus
constitutes a new class of noncoding RNA. sisRNA is detectable by RT-PCR in
samples of total RNA from embryos up to the mid-blastula stage, when zygotic
transcription begins. Storage of sisRNA in the oocyte nucleus and its
transmission to the developing embryo suggest that it may play important
regulatory roles during oogenesis and/or early embryogenesis.
PMID- 23154986
TI - Obstructive sleep apnoea and metabolic syndrome: put CPAP efficacy in a more
realistic perspective.
PMID- 23154987
TI - Prediction of peak flow values followed by feedback improves perception of lung
function and adherence to inhaled corticosteroids in children with asthma.
AB - BACKGROUND: Failure to detect respiratory compromise can lead to emergency
healthcare use and fatal asthma attacks. The purpose of this study was to examine
the effect of predicting peak expiratory flow (PEF) and receiving feedback on
perception of pulmonary function and adherence to inhaled corticosteroids (ICS).
METHODS: The sample consisted of 192 ethnic minority, inner-city children (100
Puerto Rican, 54 African-American, 38 Afro-Caribbean) with asthma and their
primary caregivers recruited from outpatient clinics in Bronx, New York.
Children's PEF predictions were entered into an electronic spirometer and
compared with actual PEF across 6 weeks. Children in one study were blinded to
PEF (n=88; no feedback) and children in a separate study were able to see PEF
(n=104; feedback) after predictions were locked in. Dosers were attached to
asthma medications to monitor use. RESULTS: Children in the feedback condition
displayed greater accuracy (p<0.001), less under-perception (p<0.001) and greater
over-perception (p<0.001) of respiratory compromise than children in the no
feedback condition. This between-group difference was evident soon after baseline
training and maintained across 6 weeks. The feedback condition displayed greater
adherence to ICS (p<0.01) and greater quick-relief medication use (p<0.01) than
the no feedback condition. CONCLUSIONS: Feedback on PEF predictions for ethnic
minority, inner-city children may decrease under-perception of respiratory
compromise and increase adherence to controller medications. Children and their
families may shift their attention to asthma perception and management as a
result of this intervention.
PMID- 23154988
TI - Your asthma reliever inhaler: never leave home without it.
PMID- 23154989
TI - Heterotopic ossification encasing a plombage cavity.
PMID- 23154990
TI - A novel antibody for human induced pluripotent stem cells and embryonic stem
cells recognizes a type of keratan sulfate lacking oversulfated structures.
AB - We have generated a monoclonal antibody (R-10G) specific to human induced
pluripotent stem (hiPS)/embryonic stem (hES) cells by using hiPS cells (Tic) as
an antigen, followed by differential screening of mouse hybridomas with hiPS and
human embryonal carcinoma (hEC) cells. Upon western blotting with R-10G, hiPS/ES
cell lysates gave a single but an unusually diffuse band at a position
corresponding to >250 kDa. The antigen protein was isolated from the induced
pluripotent stem (iPS) cell lysates with an affinity column of R-10G. The R-10G
positive band was resistant to digestion with peptide N-glycanase F (PNGase F),
neuraminidase, fucosidase, chondrotinase ABC and heparinase mix, but it
disappeared almost completely on digestion with keratanase, keratanase II and
endo-beta-galactosidase, indicating that the R-10G epitope is a keratan sulfate.
The carrier protein of the R-10G epitope was identified as podocalyxin by liquid
chromatography/mass spectrometry (LC/MS/MS) analysis of the R-10G positive
protein band material obtained on sodium dodecyl sulfate-polyacrylamide gel
electrophoresis (SDS-PAGE). The R-10G epitope is a type of keratan sulfate with
some unique properties. (1) The epitope is expressed only on hiPS/ES cells, i.e.
not on hEC cells, unlike those recognized by the conventional hiPS/ES marker
antibodies. (2) The epitope is a type of keratan sulfate lacking oversulfated
structures and is not immunologically cross-reactive with high-sulfated keratan
sulfate. (3) The R-10G epitope is distributed heterogeneously on hiPS cells,
suggesting that a single colony of undifferentiated hiPS cells consists of
different cell subtypes. Thus, R-10G is a novel antibody recognizing hiPS/ES
cells, and should be a new molecular probe for disclosing the roles of glycans on
these cells.
PMID- 23154991
TI - A comparison of exercise type and intensity on the noninvasive assessment of
skeletal muscle mitochondrial function using near-infrared spectroscopy.
AB - Near-infrared spectroscopy (NIRS) can be used to measure muscle oxygen
consumption (mVO(2)) using arterial occlusions. The recovery rate of mVO(2) after
exercise can provide an index of skeletal muscle mitochondrial function. The
purpose of this study was to test the influence of exercise modality and
intensity on NIRS measurements of mitochondrial function. Three experiments were
performed. Thirty subjects (age: 18-27 yr) were tested. NIRS signals were
corrected for blood volume changes. The recovery of mVO(2) after exercise was fit
to a monoexponential curve, and a rate constant was calculated (directly related
to mitochondrial function). No differences were found in NIRS rate constants for
VOL and ES exercises (2.04 +/- 0.57 vs. 2.01 +/- 0.59 min(-1) for VOL and ES,
respectively; P = 0.317). NIRS rate constants were independent of the contraction
frequency for both VOL and ES (VOL: P = 0.166 and ES: P = 0.780). ES current
intensity resulted in significant changes to the normalized time-tension integral
(54 +/- 11, 82 +/- 7, and 100 +/- 0% for low, medium, and high currents,
respectively; P < 0.001) but did not influence NIRS rate constants (2.02 +/-
0.54, 1.95 +/- 0.44, 2.02 +/- 0.46 min(-1) for low, medium, and high currents,
respectively; P = 0.771). In summary, NIRS measurements of skeletal muscle
mitochondrial function can be compared between VOL and ES exercises and were
independent of the intensity of exercise. NIRS represents an important new
technique that is practical for testing in research and clinical settings.
PMID- 23154992
TI - Sex differences in postsynaptic sweating and cutaneous vasodilation.
AB - The current study aimed to determine whether a peripheral modulation of sweating
contributes to the lower sudomotor thermosensitivity previously observed in
females during exercise. We examined dose-response relationships in 12 males and
12 females to incremental doses of acetylcholine (ACh) and methylcholine (MCh)
for sweating (ventilated capsule), as well as to ACh and sodium nitroprusside
(SNP) for cutaneous vasodilation (laser-Doppler). All drugs were infused using
intradermal microdialysis. On a separate day, potential sex differences in the
onset threshold and/or thermosensitivity of heat loss responses were assessed
during progressive increases in mean body temperature elicited by passive
heating. Increases in sweating as a function of increasing concentration of ACh
(P = 0.008) and MCh (P = 0.046) significantly differed between males and females.
Although the concentration eliciting 50% of the maximal sweating response did not
differ between sexes for either agonist (P > 0.1), maximum values were lower in
females in response to ACh (0.34 +/- 0.12 vs. 0.59 +/- 0.19 mg.min(-1).cm(-2), P
= 0.04) and MCh (0.48 +/- 0.12 vs. 0.78 +/- 0.26 mg.min(-1).cm(-2), P = 0.05).
This observation was paralleled by a lower thermosensitivity of sudomotor
activity in females during passive heating (1.29 +/- 0.34 vs. 1.83 +/- 0.33
mg.min(-1).cm(-2). degrees C(-1), P = 0.03), with no significant differences in
the change in mean body temperature at which onset of sweating occurred (0.85 +/-
0.19 vs. 0.67 +/- 0.13 degrees C, P = 0.10). No sex differences in cutaneous
vasodilation were observed in response to ACh and SNP, as well as during passive
heating (all P > 0.1). These findings provide direct evidence for a peripheral
modulation of sudomotor activity in females. In contrast, sex does not modulate
cutaneous vasodilation.
PMID- 23154993
TI - Vasoconstrictor responsiveness during hyperbaric hyperoxia in contracting human
muscle.
AB - Large increases in systemic oxygen content cause substantial reductions in
exercising forearm blood flow (FBF) due to increased vascular resistance. We
hypothesized that 1) functional sympatholysis (blunting of sympathetic alpha
adrenergic vasoconstriction) would be attenuated during hyperoxic exercise and 2)
alpha-adrenergic blockade would limit vasoconstriction during hyperoxia and
increase FBF to levels observed under normoxic conditions. Nine male subjects
(age 28 +/- 1 yr) performed forearm exercise (20% of maximum) under normoxic and
hyperoxic conditions. Studies were performed in a hyperbaric chamber at 1
atmosphere absolute (ATA; sea level) while breathing 21% O(2) and at 2.82 ATA
while breathing 100% O(2) (estimated change in arterial O(2) content ~6 ml
O(2)/100 ml). FBF (ml/min) was measured using Doppler ultrasound. Forearm
vascular conductance (FVC) was calculated from FBF and blood pressure (arterial
catheter). Vasoconstrictor responsiveness was determined using intra-arterial
tyramine. FBF and FVC were substantially lower during hyperoxic exercise than
normoxic exercise (~20-25%; P < 0.01). At rest, vasoconstriction to tyramine (%
decrease from pretyramine values) did not differ between normoxia and hyperoxia
(P > 0.05). During exercise, vasoconstrictor responsiveness was slightly greater
during hyperoxia than normoxia (-22 +/- 3 vs. -17 +/- 2%; P < 0.05). However,
during alpha-adrenergic blockade, hyperoxic exercise FBF and FVC remained lower
than during normoxia (P < 0.01). Therefore, our data suggest that although the
vasoconstrictor responsiveness during hyperoxic exercise was slightly greater, it
likely does not explain the majority of the large reductions in FBF and FVC (~20
25%) during hyperbaric hyperoxic exercise.
PMID- 23154994
TI - The timing of administration of a clinically relevant dose of losartan influences
the healing process after contusion induced muscle injury.
AB - Losartan (Los) is a Food and Drug Administration-approved antihypertensive
medication that has a well-tolerated side effect profile. We have demonstrated
that treatment with Los immediately after injury was effective at promoting
muscle healing and inducing an antifibrotic effect in a murine model of skeletal
muscle injury. We initially investigated the minimum effective dose of Los
administration immediately after injury and subsequently determined whether the
timing of administering a clinically relevant dose of Los would influence its
effectiveness at improving muscle healing after muscle injury. In the first part
of this study, mice were administered 3, 10, 30, or 300 mg.kg(-1).day(-1) of Los
immediately after injury, and the healing process was evaluated histologically
and physiologically 4 wk after injury. In the second study, the clinically
relevant dose of 10 mg.kg(-1).day(-1) was administered immediately or started at
3 or 7 days postinjury. The administration of 300 mg.kg(-1).day(-1) immediately
following injury led to a significant increase in muscle regeneration, a
significant decrease in fibrosis, and an improvement in muscle function.
Moreover, we observed a significant decrease in fibrosis and a significant
increase in muscle regeneration at 4 wk postinjury, when the clinically relevant
dose of 10 mg.kg(-1).day(-1) was administered at 3 or 7 days postinjury.
Functional evaluation also demonstrated a significant improvement compared with
the injured untreated control when Los treatment was initiated 3 days after
injury. Our study revealed accelerated muscle healing when the 300 mg.kg(-1).day(
1) of Los was administered immediately after injury and a clinically relevant
dose of 10 mg.kg(-1).day(-1) of Los was administered at 3 or 7 days postinjury.
PMID- 23154995
TI - The effect of hypoxemia and exercise on acute mountain sickness symptoms.
AB - Performing exercise during the first hours of hypoxic exposure is thought to
exacerbate acute mountain sickness (AMS), but whether this is due to increased
hypoxemia or other mechanisms associated with exercise remains unclear. In 12
healthy men, AMS symptoms were assessed during three 11-h experimental sessions:
1) in Hypoxia-exercise, inspiratory O(2) fraction (Fi(O(2))) was 0.12, and
subjects performed 4-h cycling at 45% Fi(O(2))-specific maximal power output from
the 4th to the 8th hour; 2) in Hypoxia-rest, Fi(O(2)) was continuously adjusted
to match the same arterial oxygen saturation as in Hypoxia-exercise, and subjects
remained at rest; and 3) in Normoxia-exercise, Fi(O(2)) was 0.21, and subjects
cycled as in Hypoxia-exercise at 45% Fi(O(2))-specific maximal power output. AMS
scores did not differ significantly between Hypoxia-exercise and Hypoxia-rest,
while they were significantly lower in Normoxia-exercise (Lake Louise score: 5.5
+/- 2.1, 4.4 +/- 2.4, and 2.3 +/- 1.5, and cerebral Environmental Symptom
Questionnaire: 1.2 +/- 0.7, 1.0 +/- 1.0, and 0.3 +/- 0.4, in Hypoxia-exercise,
Hypoxia-rest, and Normoxia-exercise, respectively; P < 0.01). Headache scored by
visual analog scale was higher in Hypoxia-exercise and Hypoxia-rest compared with
Normoxia-exercise (36 +/- 22, 35 +/- 25, and 5 +/- 6, P < 0.001), while the
perception of fatigue was higher in Hypoxia-exercise compared with Hypoxia-rest
(60 +/- 24, 32 +/- 22, and 46 +/- 23, in Hypoxia-exercise, Hypoxia-rest, and
Normoxia-exercise, respectively; P < 0.01). Despite significant physiological
stress during hypoxic exercise and some AMS symptoms induced by normoxic cycling
at similar relative workload, exercise does not significantly worsen AMS severity
during the first hours of hypoxic exposure at a given arterial oxygen
desaturation. Hypoxemia per se appears, therefore, to be the main mechanism
underlying AMS, whether or not exercise is performed.
PMID- 23154997
TI - A survey of primary care doctors in ten countries shows progress in use of health
information technology, less in other areas.
AB - Health reforms in high-income countries increasingly aim to redesign primary care
to improve the health of the population and the quality of health care services,
and to address rising costs. Primary care improvements aim to provide patients
with better access to care and develop more-integrated care systems through
better communication and teamwork across sites of care, supported by health
information technology and feedback to physicians on their performance. Our
international survey of primary care doctors in Australia, Canada, France,
Germany, the Netherlands, New Zealand, Norway, Switzerland, the United Kingdom,
and the United States found progress in the use of health information technology
in health care practices, particularly in the United States. Yet a high
percentage of primary care physicians in all ten countries reported that they did
not routinely receive timely information from specialists or hospitals. Countries
also varied notably in the extent to which physicians received information on
their own performance. In terms of access, US doctors were the most likely to
report that they spent substantial time grappling with insurance restrictions and
that their patients often went without care because of costs. Signaling the need
for reforms, the vast majority of US doctors surveyed said that the health care
system needs fundamental change.
PMID- 23154996
TI - Cardiac mechanics are impaired during fatiguing exercise and cold pressor test in
healthy older adults.
AB - We sought to determine how the aging left ventricle (LV) responds to sympathetic
nervous system (SNS) activation. Three separate echocardiographic experiments
were conducted in 11 healthy young (26 +/- 1 yr) and 11 healthy older (64 +/- 1
yr) adults. Tissue Doppler imaging was used to measure systolic myocardial
velocity (S(m)), early diastolic myocardial velocity (E(m)), and late diastolic
myocardial velocity (A(m)) during isometric fatiguing handgrip (IFHG), a 2-min
cold pressor test (CPT), and 5 min of normobaric hypoxia. Heart rate (HR) and
mean arterial pressure (MAP) were also monitored on a beat-by-beat basis; rate
pressure product (RPP) was used as an index of myocardial oxygen demand. At peak
IFHG, the groups had similar increases in RPP, but the DeltaS(m) was
significantly greater (i.e., larger impairment) in the older subjects (-0.82 +/-
0.13 cm/s) compared with the young subjects (0.37 +/- 0.30 cm/s). At peak IFHG,
the DeltaE(m) was similar between older (-1.59 +/- 0.68 cm/s) and young subjects
(-1.06 +/- 0.76 cm/s). In response to the CPT, both S(m) and E(m) were reduced in
the older adults but did not change relative to baseline in the young subjects.
Normobaric hypoxia elevated HR and RPP in both groups but did not alter Tissue
Doppler parameters. These data indicate that S(m) and E(m) are reduced in healthy
older adults during IFHG and CPT. We speculate that suboptimal LV adaptations to
SNS stress may partly explain why acute heavy exertion can trigger myocardial
ischemia.
PMID- 23154998
TI - A mixed-method examination of food marketing directed towards children in
Australian supermarkets.
AB - The purpose of this study was to determine the prevalence of children's food
requests, and parents' experiences of food marketing directed towards children,
in the supermarket environment. A mixed-method design was used. Firstly,
intercept interviews were conducted with parents accompanied by a child/children
on exiting supermarkets (sampled from a large regional centre in Australia).
Parents were asked about the prevalence and types of food requests by
child/children during their supermarket visit and whether they purchased these
foods. Secondly, focus groups (n = 13) and telephone interviews (n = 3) were
conducted exploring parents' experiences of supermarket shopping with children
and the impact of child-directed marketing. Of the 158 intercept survey
participants (30% response rate), 73% reported a food request during the
supermarket visit. Most requested food items (88%) were unhealthy foods, with
chocolate/confectionery being the most common food category requested (40%). Most
parents (70%) purchased at least one food item requested during the shopping
trip. Qualitative interviews identified four themes associated with food requests
and prompts in the supermarket: parents' experience of pester power in the
supermarket; prompts for food requests in the supermarket; parental responses to
pestering in the supermarket environment, and; strategies to manage pestering and
minimize requests for food items. Food requests from children are common during
supermarket shopping. Despite the majority of the requests being unhealthy,
parents often purchase these foods. Parents reported difficulties dealing with
constant requests and expressed desire for environmental changes including
confectionery-free checkouts, minimization of child friendly product placement
and reducing children's exposure to food marketing.
PMID- 23154999
TI - The HSP90 inhibitor geldanamycin perturbs endosomal structure and drives
recycling ErbB2 and transferrin to modified MVBs/lysosomal compartments.
AB - The ErbB2 receptor is a clinically validated cancer target whose internalization
and trafficking mechanisms remain poorly understood. HSP90 inhibitors, such as
geldanamycin (GA), have been developed to target the receptor to degradation or
to modulate downstream signaling. Despite intense investigations, the entry route
and postendocytic sorting of ErbB2 upon GA stimulation have remained
controversial. We report that ErbB2 levels inversely impact cell clathrin
mediated endocytosis (CME) capacity. Indeed, the high levels of the receptor are
responsible for its own low internalization rate. GA treatment does not directly
modulate ErbB2 CME rate but it affects ErbB2 recycling fate, routing the receptor
to modified multivesicular endosomes (MVBs) and lysosomal compartments, by
perturbing early/recycling endosome structure and sorting capacity. This activity
occurs irrespective of the cargo interaction with HSP90, as both ErbB2 and the
constitutively recycled, HSP90-independent, transferrin receptor are found within
modified endosomes, and within aberrant, elongated recycling tubules, leading to
modified MVBs/lysosomes. We propose that GA, as part of its anticancer activity,
perturbs early/recycling endosome sorting, routing recycling cargoes toward mixed
endosomal compartments.
PMID- 23155000
TI - Small heat shock proteins target mutant cystic fibrosis transmembrane conductance
regulator for degradation via a small ubiquitin-like modifier-dependent pathway.
AB - Small heat shock proteins (sHsps) bind destabilized proteins during cell stress
and disease, but their physiological functions are less clear. We evaluated the
impact of Hsp27, an sHsp expressed in airway epithelial cells, on the common
protein misfolding mutant that is responsible for most cystic fibrosis. F508del
cystic fibrosis transmembrane conductance regulator (CFTR), a well-studied
protein that is subject to cytosolic quality control, selectively associated with
Hsp27, whose overexpression preferentially targeted mutant CFTR to proteasomal
degradation. Hsp27 interacted physically with Ubc9, the small ubiquitin-like
modifier (SUMO) E2 conjugating enzyme, implying that F508del SUMOylation leads to
its sHsp-mediated degradation. Enhancing or disabling the SUMO pathway increased
or blocked Hsp27's ability to degrade mutant CFTR. Hsp27 promoted selective
SUMOylation of F508del NBD1 in vitro and of full-length F508del CFTR in vivo,
which preferred endogenous SUMO-2/3 paralogues that form poly-chains. The SUMO
targeted ubiquitin ligase (STUbL) RNF4 recognizes poly-SUMO chains to facilitate
nuclear protein degradation. RNF4 overexpression elicited F508del degradation,
whereas Hsp27 knockdown blocked RNF4's impact on mutant CFTR. Similarly, the
ability of Hsp27 to degrade F508del CFTR was lost during overexpression of
dominant-negative RNF4. These findings link sHsp-mediated F508del CFTR
degradation to its SUMOylation and to STUbL-mediated targeting to the ubiquitin
proteasome system and thereby implicate this pathway in the disposal of an
integral membrane protein.
PMID- 23155001
TI - Competitive binding of CUGBP1 and HuR to occludin mRNA controls its translation
and modulates epithelial barrier function.
AB - RNA-binding proteins CUG-binding protein 1 (CUGBP1) and HuR are highly expressed
in epithelial tissues and modulate the stability and translation of target mRNAs.
Here we present evidence that CUGBP1 and HuR jointly regulate the translation of
occludin and play a crucial role in the maintenance of tight junction (TJ)
integrity in the intestinal epithelial cell monolayer. CUGBP1 and HuR competed
for association with the same occludin 3'-untranslated region element and
regulated occludin translation competitively and in opposite directions. CUGBP1
overexpression decreased HuR binding to occludin mRNA, repressed occludin
translation, and compromised the TJ barrier function, whereas HuR overexpression
inhibited CUGBP1 association with occludin mRNA and promoted occludin
translation, thereby enhancing the barrier integrity. Repression of occludin
translation by CUGBP1 was due to the colocalization of CUGBP1 and tagged occludin
RNA in processing bodies (P-bodies), and this colocalization was prevented by HuR
overexpression. These findings indicate that CUGBP1 represses occludin
translation by increasing occludin mRNA recruitment to P-bodies, whereas HuR
promotes occludin translation by blocking occludin mRNA translocation to P-bodies
via the displacement of CUGBP1.
PMID- 23155002
TI - SmgGDS antagonizes BPGAP1-induced Ras/ERK activation and neuritogenesis in PC12
cell differentiation.
AB - BPGAP1 is a Rho GTPase-activating protein (RhoGAP) that regulates cell
morphogenesis, cell migration, and ERK signaling by the concerted action of its
proline-rich region (PRR), RhoGAP domain, and the BNIP-2 and Cdc42GAP homology
(BCH) domain. Although multiple cellular targets for the PRR and RhoGAP have been
identified, and their functions delineated, the mechanism by which the BCH domain
regulates functions of BPGAP1 remains unclear. Here we show that its BCH domain
induced robust ERK activation leading to PC12 cell differentiation by targeting
specifically to K-Ras. Such stimulatory effect was inhibited, however, by both
dominant-negative mutants of Mek2 (Mek2-K101A) and K-Ras (K-Ras-S17N) and also by
the small G-protein GDP dissociation stimulator (SmgGDS). Consequently SmgGDS
knockdown released this inhibition and resulted in a superinduction of K-Ras
activation and PC12 differentiation mediated by BCH domain. These results
demonstrate the versatility of the BCH domain of BPGAP1 in regulating ERK
signaling by involving K-Ras and SmgGDS and support the unique role of BPGAP1 as
a dual regulator for Ras and Rho signaling in cell morphogenesis and
differentiation.
PMID- 23155004
TI - Inferring population histories using genome-wide allele frequency data.
AB - The recent development of high-throughput genotyping technologies has
revolutionized the collection of data in a wide range of both model and nonmodel
species. These data generally contain huge amounts of information about the
demographic history of populations. In this study, we introduce a new method to
estimate divergence times on a diffusion time scale from large single-nucleotide
polymorphism (SNP) data sets, conditionally on a population history that is
represented as a tree. We further assume that all the observed polymorphisms
originate from the most ancestral (root) population; that is, we neglect
mutations that occur after the split of the most ancestral population. This
method relies on a hierarchical Bayesian model, based on Kimura's time-dependent
diffusion approximation of genetic drift. We implemented a Metropolis-Hastings
within Gibbs sampler to estimate the posterior distribution of the parameters of
interest in this model, which we refer to as the Kimura model. Evaluating the
Kimura model on simulated population histories, we found that it provides
accurate estimates of divergence time. Assessing model fit using the deviance
information criterion (DIC) proved efficient for retrieving the correct tree
topology among a set of competing histories. We show that this procedure is
robust to low-to-moderate gene flow, as well as to ascertainment bias, providing
that the most distantly related populations are represented in the discovery
panel. As an illustrative example, we finally analyzed published human data
consisting in genotypes for 452,198 SNPs from individuals belonging to four
populations worldwide. Our results suggest that the Kimura model may be helpful
to characterize the demographic history of differentiated populations, using
genome-wide allele frequency data.
PMID- 23155003
TI - Ancient properties of spider silks revealed by the complete gene sequence of the
prey-wrapping silk protein (AcSp1).
AB - Spider silk fibers have impressive mechanical properties and are primarily
composed of highly repetitive structural proteins (termed spidroins) encoded by a
single gene family. Most characterized spidroin genes are incompletely known
because of their extreme size (typically >9 kb) and repetitiveness, limiting
understanding of the evolutionary processes that gave rise to their unusual gene
architectures. The only complete spidroin genes characterized thus far form the
dragline in the Western black widow, Latrodectus hesperus. Here, we describe the
first complete gene sequence encoding the aciniform spidroin AcSp1, the primary
component of spider prey-wrapping fibers. L. hesperus AcSp1 contains a single
enormous (~19 kb) exon. The AcSp1 repeat sequence is exceptionally conserved
between two widow species (~94% identity) and between widows and distantly
related orb-weavers (~30% identity), consistent with a history of strong
purifying selection on its amino acid sequence. Furthermore, the 16 repeats (each
371-375 amino acids long) found in black widow AcSp1 are, on average, >99%
identical at the nucleotide level. A combination of stabilizing selection on
amino acid sequence, selection on silent sites, and intragenic recombination
likely explains the extreme homogenization of AcSp1 repeats. In addition,
phylogenetic analyses of spidroin paralogs support a gene duplication event
occurring concomitantly with specialization of the aciniform glands and the
tubuliform glands, which synthesize egg-case silk. With repeats that are
dramatically different in length and amino acid composition from dragline
spidroins, our L. hesperus AcSp1 expands the knowledge base for developing silk
based biomimetic technologies.
PMID- 23155006
TI - Characterization of Staphylococcus xylosus isolated from broiler chicken barn
bioaerosol.
AB - In this study we isolated and characterized Staphylococcus xylosus, a coagulase
negative staphylococcal species considered as commensal and one of the prevalent
staphylococcal species found in poultry bioaerosol. Isolates were obtained using
air samplers and selective phenylethyl alcohol agar for gram-positive bacteria
during 35-d periods at different times of the day. A total of 200 colonies were
recovered and after basic biochemical tests were performed, presumptive
staphylococci were subsequently identified by API Staph strips. A total of 153
(76.5%) staphylococci were found, among which 84 were S. xylosus (46 and 38
isolated inside and outside, respectively). Biofilm formation was observed in
86.9% of S. xylosus isolates, whereas 79.8% of them showed hemolytic activity.
There was a strong correlation (92.5%) between biofilm formation and hemolytic
activity. All 84 S. xylosus isolates were susceptible to amikacin,
ampicillin/sulbactam, chloramphenicol, ciprofloxacin, gentamycin, kanamycin,
linezolid, trimethoprim/sulfamethoxazole, and vancomycin. Resistance to nalidixic
acid (86.9%), novobiocin (85.7%), penicillin (70.2%), lincomycin (46.4%),
oxacillin (42.9%), ampicillin (27.4%), tetracycline (21.4%), erythromycin
(11.9%), bacitracin (10.7%), and streptomycin (2.4%) was observed among the
isolates. Resistance to tetracycline, lincomycin, erythromycin, and beta-lactam
antibiotics was occasionally linked to the tetK, linA, ermB, and blaZ genes,
respectively. Random amplification of polymorphic DNA results showed similarity
of 15 to 99% between isolates collected outside and inside the barn, indicating
genetic diversity of these isolates. Our study indicates that characterization of
poultry bioaerosol coagulase-negative staphylococcal species such as S. xylosus
is necessary for assessing their safety status for both poultry and humans.
PMID- 23155005
TI - Functional evolution of an anthocyanin pathway enzyme during a flower color
transition.
AB - Dissecting the genetic basis for the evolution of species differences requires a
combination of phylogenetic and molecular genetic perspectives. By mapping the
genetic changes and their phenotypic effects onto the phylogeny, it is possible
to distinguish changes that may have been directly responsible for a new
character state from those that fine tune the transition. Here, we use
phylogenetic and functional methods to trace the evolution of substrate
specificity in dihydroflavonol-4-reductase (Dfr), an anthocyanin pathway gene
known to be involved in the transition from blue to red flowers in Iochroma.
Ancestral state reconstruction indicates that three substitutions occurred during
the flower color transition, whereas several additional substitutions followed
the transition. Comparisons of enzymatic function between ancestral proteins in
blue- and red-flowered lineages and proteins from present-day taxa demonstrate
that evolution of specificity for red pigment precursors was caused by the first
three substitutions, which were fixed by positive selection and which differ from
previously documented mutations affecting specificity. Two inferred substitutions
subsequent to the initial flower color transition were also adaptive and resulted
in an additional increase in specificity for red precursors. Epistatic
interactions among both sets of substitutions may have limited the order of
substitutions along branches of the phylogeny leading from blue-pigmented
ancestors to the present-day red-flowered taxa. These results suggest that the
species differences in DFR specificity may arise by a combination of selection on
flower color and selection for improved pathway efficiency but that the exact
series of genetic changes resulting in the evolution of specificity is likely to
be highly contingent on the starting state.
PMID- 23155007
TI - Effect of combinations of monochromatic lights on growth and productive
performance of broilers.
AB - Our previous study suggested that green light promotes broiler growth during the
early stage [posthatching day (P) 0 to P26], and blue light enhances growth
during the later stage (P27 to P49). The purpose of this study was to improve
broiler growth and productive performance by using a combination of monochromatic
lights at critical points between the early and later stages of growth. A total
of 512 male Arbor Acres broilers on P0 were reared under white light (W), red
light (R), green light (G), and blue light (B) by using light-emitting diode
lamps at 15 +/- 0.2 lx from P0 to P26 (16 replicate pens/group, 8 birds/pen), and
then switching to another color of light until P49 (4 replicate pens/group, 8
birds/pen). As compared with single monochromatic lights, broilers reared in
environments under combinations of monochromatic lights, W->G, R->B, G->B, and B
>G, attained heavier BW than those reared in environments under W->W (3.18 to
12.00%), R->R (1.96 to 18.14%), G->G (0.85 to 5.08%), and B->B (0.39 to 4.70%),
respectively. In addition, feed conversion ratios in the W->B, R->B, and G->B
combinations were lower than feed conversion ratios for W->W (15.86%, P < 0.05),
R->R (18.41%, P < 0.05), and G->G (3.37%), respectively. Moreover, the
eviscerated carcass weight and breast, thigh, and crus muscle weights under G->B
were greater by 0.40 to 56.23% than were those for the other light groups except
W->B (eviscerated carcass) and B->G (breast muscle). The results suggest that the
application of the G->B and B->G exchanges can be used successfully to improve
growth and productive performance in broilers.
PMID- 23155008
TI - Associations of chicken Mx1 polymorphism with antiviral responses in avian
influenza virus infected embryos and broilers.
AB - Avian influenza virus (AIV) is a major respiratory disease of poultry that causes
catastrophic losses to the poultry industry. The Mx protein has been shown to
confer antiviral responses to influenza viruses in mice. One nonsynonymous
substitution (S631N) in the chicken Mx protein is reported to be associated with
resistance to AIV infection in vitro. The previous studies suggested controversy
over whether this substitution in the Mx protein plays an important antiviral
role in AIV infection in the chicken. It would be intriguing to investigate if
the substitution is associated with resistance to AIV infection both in ovo and
in vivo in chickens. In this study, the embryos and young chicks were generated
from the cross of Mx1 heterozygous (S631N) parents with an expected segregating
ratio of 1:2:1 in the progeny. A PCR length polymorphism was developed to
genotype the Mx1 gene from 119 embryos and 48 chickens. The embryonated chicken
eggs were inoculated with 10(6) 50% embryo infectious dose (EID(50)) H5N9 AIV on
d 13. Hemagglutinating units in allantoic fluid were determined at 48 h
postinoculation. For the in vivo study, twenty-four 1-wk-old broilers were
inoculated with 10(6) EID(50) H5N3, and virus titers in lungs were evaluated at d
4 postinoculation. This is the first report revealing no significant association
between Mx1 genotypes and low pathogenesis AIV infection both in ovo and in vivo
in the chicken. Total RNA samples were isolated from chicken lung tissues in the
in vivo study, and the Mx1 mRNA expression assay among 3 genotypes also suggested
that only heterozygote birds had significantly greater expression with AIV
infection than noninfected birds. A recombination breakpoint within Mx1 gene was
also first identified, which has laid a solid foundation for further
understanding biological function of the Mx1 gene in chickens. The current study
provides valuable information on the effect of the Mx1 gene on the genetic
resistance to AIV in chickens, and Mx1 will not be applicable for enhancing
genetic resistance to AIV infection in chickens.
PMID- 23155009
TI - Egg quality traits differ in hens selected for high as compared with low antibody
response to sheep red blood cells.
AB - White Leghorn chickens were selected for 36 generations for high (HAS) or low
(LAS) antibody response to SRBC 5 d after an intravenous challenge. Our objective
was to determine differences in egg quality resulting from that selection. In
total, eggs from 45 hens from each line were assessed for shape index (SI),
weight (WT, g), albumen height (AH, mm), Haugh units (HU), yolk color (YC), and
eggshell weight (ESW, g) and thickness (EST, mm). Three cycles representing
early, middle, and late stages of production were examined. Eggs from HAS hens
had higher SI scores (4.12 +/- 0.55; P < 0.001) and greater AH (0.27 +/- 0.12; P
< 0.001) and HU (1.89 +/- 0.91; P = 0.04) than LAS hens; conversely, eggs from
LAS hens had greater EST (0.03 +/- 0.01 g; P < 0.001) and heavier ESW (0.66 +/-
0.09 g; P < 0.001) than HAS hens. Lines were similar for WT and YC (P > 0.52).
Albumen height and HU decreased (P < 0.001), whereas WT, ESW, and EST increased
(P < 0.001) over cycles for both lines. However, SI decreased in LAS hens, yet
increased in HAS hens, across cycles (P < 0.001). An interaction between line and
cycle was observed in WT, SI, ESW, and EST (P < 0.001), but only for WT did the
interaction cause re-ranking across cycles. Egg quality was, generally, superior
in HAS compared with LAS hens, suggesting that higher antibody response may
maintain overall fitness.
PMID- 23155010
TI - Twenty-five years of selection for improved leg health in purebred broiler lines
and underlying genetic parameters.
AB - Leg health is an important component of broiler welfare and the economics of
broiler production. This study presents the development of leg health in 3
purebred commercial broiler lines during 25 yr of selection and investigates the
genetic background of leg health traits in current populations of these lines.
The leg health traits were deformities of the long bones (LD) and crooked toes
(CT), recorded since 1985, and tibial dyschondroplasia (TD) and hock burn (HB),
recorded since 1990. The prevalence of CT and HB decreased mainly in the first
decade (range among lines -1.2 to -2.3% and -1.3 to -1.5% per year,
respectively), after which it stabilized at low levels. The prevalence of LD and
TD decreased by -0.6 to -0.9% and -0.4 to -1.2% per year, respectively. Genetic
parameters were estimated using data from 4 recent generations. The BW ranged
from 2.0 to 2.4 kg at 5 wk of age; the prevalences of LD, CT, TD, and HB from 8.6
to 12.9%, 0.6 to 2.6%, 4.6 to 8.0%, and 4.0 to 12.2%, respectively. Estimates of
heritability were 0.04 to 0.07 for LD, 0.01 to 0.10 for CT, 0.10 to 0.27 for TD,
and 0.06 to 0.09 for HB (all SE <=0.01). Estimates of the genetic correlations
between LD and CT were 0.11 to 0.43 (all SE <=0.09), between these traits and HB
were negligible, and of TD with LD, CT, and HB were -0.26 to 0.16 (all SE
<=0.11). Estimates of genetic correlations between the leg health traits and BW
were lowly to moderately unfavorable, ranging from 0.09 to 0.37 (all SE <=0.06).
The differences between the lines suggest that strategies for simultaneous
improvement of all traits tailored for each line individually have been
effective. This research demonstrates the long-term effectiveness of selection
for improving leg health in broilers and highlights that, despite somewhat
unfavorable genetic correlations with BW, these traits can be improved
simultaneously in a balanced breeding program.
PMID- 23155011
TI - Breeding for high specific immune reactivity affects sensitivity to the
environment.
AB - Lipopolysaccharides (LPS) are present in high levels in the air of chicken houses
and likely have immune-modulating effects. In this study, layers from the 30th
generation of a divergent selection experiment for humoral immune reactivity to
subcutaneously administered sheep red blood cells were concurrently
intratracheally challenged with human serum albumin (HuSA) and LPS at 7 and 12 wk
of age following a crossing over design. Chickens selected for high humoral
immune reactivity (H line) showed higher specific antibody responses to
intratracheally administered HuSA and a higher level of natural antibody binding
keyhole limpet hemocyanin compared with chickens genetically selected for low
humoral immune reactivity (L line), and were also more sensitive to immune
modulation by LPS at 7 wk of age. Body weight gain was negatively affected by LPS
at 7 wk of age in the L line, but after 12 wk of age in the H line. Egg
production was lower and delayed in the H line. We conclude that these chicken
selection lines differ in sensitivity to the environment (LPS), and consequently
may therefore also react differently to infection, vaccinations, and other immune
responses. In addition, selection for immune responsiveness affected growth and
egg lay.
PMID- 23155012
TI - Avian infectious bronchitis and deep pectoral myopathy - a case control study.
AB - Infectious bronchitis is caused by a coronavirus, infectious bronchitis virus
(IBV). Infectious bronchitis is an acute and highly contagious disease of
economic importance due to the reduction in weight gain observed with infected
broilers and the drop in egg quality and production associated with infected
laying hens. The presence of deep pectoral myopathy has been associated with IBV
variants. This lesion is detected at slaughterhouses and is characterized by
paleness and atrophy of the deep pectoral muscle, including necrosis of the
region, leading to condemnations of the breast muscle, a valuable meat cut in the
market. This work aimed to study the relationship between deep pectoral myopathy
and IBV by describing tracheal and muscle lesions and comparing the frequency of
IBV detection via reverse-transcription (RT) PCR in muscle, tracheal, and cecal
tonsil samples from broilers with and without myopathy. A case-control study was
conducted in 40 broiler flocks vaccinated with the Massachusetts strain. The case
group consisted of 23 flocks that presented myopathic lesions under sanitary
inspection and a control group of 17 flocks without myopathic lesions. The
tracheal, cecal tonsil, and supracoracoid muscle (with and without lesions)
samples from the 40 broiler flocks were screened by RT-PCR to detect IBV.
Histopathology of muscle and tracheal tissue was carried out. Upon microscopic
examination, the muscle samples from the case group presented extensive necrosis,
intense mononuclear inflammatory infiltration, muscle fiber fragmentation, and
fibrotic tissue, confirming myopathy, whereas muscles from the control group
showed no alterations. The tracheal samples presented a large number of
infiltrated mononuclear inflammatory cells that in some areas formed submucosal
nodules. A total of 25 flocks tested IBV positive by RT-PCR: 14 from the case
group and 11 from the control group. The IBV was detected by RT-PCR directly in
muscle samples. Despite that, the relationship between deep pectoral myopathy and
IBV was not established. The higher positive IBV RT-PCR percentage noted in the
cecal tonsil samples demonstrates how important the choice of organs is for
diagnostic purposes.
PMID- 23155013
TI - Comparison of water-based foam and carbon dioxide gas mass emergency depopulation
of White Pekin ducks.
AB - The mass depopulation of production birds remains an effective means of
controlling fast-moving, highly infectious diseases such as avian influenza and
virulent Newcastle disease. Two experiments were performed to compare the
physiological responses of White Pekin commercial ducks during foam depopulation
and CO(2) gas depopulation. Both experiment 1 (5 to 9 wk of age) and 2 (8 to 14
wk of age) used electroencephalogram, electrocardiogram, and accelerometer to
monitor and evaluate the difference in time to unconsciousness, motion cessation,
brain death, altered terminal cardiac activity, duration of bradycardia, and
elapsed time from onset of bradycardia to onset of unconsciousness between foam
and CO(2) gas. Experiment 2 also added a third treatment, foam + atropine
injection, to evaluate the effect of suppressing bradycardia. Experiment 1
resulted in significantly shorter times for all 6 physiological points for CO(2)
gas compared with foam, whereas experiment 2 found that there were no significant
differences between foam and CO(2) gas for these physiological points except
brain death, in which CO(2) was significantly faster than foam and duration of
bradycardia, which was shorter for CO(2). Experiment 2 also determined there was
a significant positive correlation between duration of bradycardia and time to
unconsciousness, motion cessation, brain death, and altered terminal cardiac
activity. The time to unconsciousness, motion cessation, brain death, and altered
terminal cardiac activity was significantly faster for the treatment foam +
atropine injection compared with foam. Both experiments showed that bradycardia
can occur as a result of either submersion in foam or exposure to CO(2) gas. The
duration of bradycardia has a significant impact on the time it takes White Pekin
ducks to reach unconsciousness and death during depopulation.
PMID- 23155014
TI - Reduced lesions in chickens with Clostridium perfringens-induced necrotic
enteritis by Lactobacillus fermentum 1.20291.
AB - Previous studies have demonstrated that Lactobacillus has anti-inflammatory
properties, but the protective functions of Lactobacillus and mechanisms of
inhibition of necrotic enteritis (NE) in the intestines of chickens have not been
fully clarified. In the present study, we selected a probiotic strain,
Lactobacillus fermentum 1.2029, which has good adhesive ability and a high
survival rate in low pH and bile salts. The objective of this study was to
examine the anti-inflammatory properties of L. fermentum 1.2029 against NE in
chickens. Two hundred forty 1-d-old male Arbor Acres broilers were blocked into 3
experimental groups as follows: (I) nonchallenge control group, (II) Clostridium
perfringens challenge group, and (III) C. perfringens challenge + L. fermentum
1.2029 group. Lactobacillus fermentum 1.2029 (1.0 mL/d, 10(8) cfu/mL) was orally
administered daily to group III during the course of the experiment, and all
uninfected control chickens were inoculated accordingly with the same volume of
PBS. Clostridium perfringens (0.5 mL on d 1 and 1.0 mL on d 14 to 21, 10(8)
cfu/mL) was administered to chickens in group II. At 28 d, scoring of gross NE
lesions was performed. Ileal segments of approximately 2 cm from 24 chickens in
each experimental group were collected and fixed in 4% (wt/vol) neutral-buffered
formalin solution for histological scoring. Ileal mucosa samples were also
collected for mRNA analysis by real-time PCR. The results showed that L.
fermentum 1.2029 reduced the severity of NE lesions in chickens. Histological
scores revealed that L. fermentum 1.2029 also reduced the inflammation damage of
NE in chickens. Changes in cytokines and Toll-like receptors (TLR) were
determined, and L. fermentum 1.2029 was found to increase interleukin-10 levels
and reduce interferon-gamma and TLR2 levels in NE-infected chickens. The results
showed that L. fermentum 1.2029 was able to regulate the intestinal mucosal
immune response and ameliorate inflammation by changing expression levels of
cytokines and TLR.
PMID- 23155015
TI - Mycoplasma gallisepticum transmission: comparison of commercial F-strain vaccine
versus layer complex-derived field strains in a tunnel ventilated house.
AB - Two simultaneous trials were conducted using a commercially available, live, F
strain Mycoplasma gallisepticum (FMG) vaccine (trial 1) or 2 inocula of layer
complex-derived MG strains (LCD-MG; trial 2). In each of the 2 trials, 4
commercial turkeys were housed in each of 2 adjoining pens immediately adjacent
to air inlets. The turkeys (8/trial) were inoculated in the right eye with either
a 1* dose of FMG (trial 1) or with 0.02 mL of 1 of 2 actively growing LCD-MG
inocula (4 turkeys/inoculum; trial 2). In each of the 2 trials, one pen housing 4
inoculated turkeys was maintained without the addition of other poultry, whereas
16 MG-free broilers and 4 MG-free layers were added to the other pen of 4
inoculated turkeys. Within each of the trials and at increasing intervals, either
4 layers (3 pens) or 4 turkeys (3 pens) were placed down-airstream from the
inoculated pens. The distance of the first pen from the inoculated turkeys was
separated by the width of one pen that was empty. Succeeding down-airstream pens
were situated such that the empty distance (absence of any poultry) between pens
that contained poultry doubled from one pen to the next such that the final pen
that contained poultry had 4 empty pens between it and the next up-airstream pen
that also contained poultry. At 106 d postinoculation, all poultry were bled,
swabbed for MG from the choanal cleft, and then euthanized and necropsied. No
commingled poultry in trial 1 (FMG), whether inoculated (turkeys) or commingled
(layers and broilers), died during the course of the trial, and 5 of the 8 FMG
vaccinated turkeys exhibited serological but not cultural evidence of
mycoplasmosis. In trial 2 (LCD-MG), 2 commingled broilers died and no inoculated
turkeys exhibited either serological or cultural evidence of mycoplasmosis. In
both trials, no poultry housed down-airstream from the inoculated poultry showed
evidence of clinical signs of mycocplasmosis and none showed either serological
or cultural evidence of mycoplasmosis.
PMID- 23155016
TI - Simultaneous detection of Clostridium perfringens and Clostridium colinum by
duplex-polymerase chain reaction.
AB - In this study, we provide a protocol for detection of Clostridium colinum and
Clostridium perfringens by the single-tube duplex-PCR (dPCR) test for
simultaneous and specific detection of both bacteria from pure cultures and fecal
samples spiked with these pathogens. Specific primers for each pathogen were
selected that amplified products of predicted sizes from bacteria in the dPCR as
well as in the single-tube PCR (sPCR) assays. The sensitivity and specificity of
dPCR assay were compared with those of the sPCR. No product amplification was
obtained with DNA from reference strains belonging to the genus Clostridium
(except C. colinum and C. perfringens) and isolates belonging to other genera
using these primer sets. The dPCR assay was as sensitive as the sPCR assay
because bacterial detection limits were similar in both assays. The detection
limits of sPCR and dPCR in bacterial suspension were 20 and 25 cfu/mL for C.
colinum and C. perfringens, respectively. Meanwhile, in the presence of feces the
sensitivity of both assays decreased to a detection limit of 1.25 * 10(4) and
1.94 * 10(4) cfu/g of feces for C. colinum and C. perfringens, respectively. In
summary, dPCR assay holds potential to be an economical and rapid diagnostic
method for the simultaneous detection of C. colinum and C. perfringens in pure
cultures and could be used to screen fecal samples for the presence of these
pathogens.
PMID- 23155017
TI - Characterization of low-pathogenicity H5 and H7 Korean avian influenza viruses in
chickens.
AB - To date, all isolated highly pathogenic avian influenza (HPAI) viruses that cause
systemic infection with a high mortality rate in poultry species have been known
to belong to either the H5 or H7 subtypes. The HPAI viruses may originate because
of the insertion of multiple basic amino acids at the cleavage site of the
hemagglutinin protein after the low-pathogenic H5 and H7 viruses have been
introduced into poultry. In the present study, we investigated the phylogenetic
characteristics of the H5 (n = 4) and H7 (n = 3) low-pathogenic avian influenza
(LPAI) viruses isolated from wild birds in Korea by using nucleotide sequences of
all 8 gene segments of the viral genome. Further, we evaluated the infectivity,
transmissibility, and pathogenic potential of these viruses in chickens.
Phylogenetic analysis showed that all viruses used in the study clustered in the
Eurasian lineage and were similar to the viruses isolated in Asian countries that
share the East Asian-Australasian migratory bird flyway. Our H5N2 isolates could
not be replicated and transmitted in chickens, but the H7N8 isolates could
efficiently be replicated and transmitted to contact-exposure chickens. In
addition, because our H7N8 isolates caused watery diarrhea in chickens, these
viruses cannot only serve as progenitors of novel HPAI strains but also
potentially cause clinical disease in poultry. Although there have been no
reports of LPAI mutation to HPAI in these regions, the wild bird surveillance
effort should focus on monitoring the introduction and transmission of the HPAI
H5N1 and LPAI H5 and H7 viruses.
PMID- 23155018
TI - Immunomodulatory activity accompanying chicken egg yolk immunoglobulin Y.
AB - Immunity transfer from a mother to the newborn does not depend exclusively on
immunoglobulins. Peptides, which are characterized by immunoregulatory properties
that accompany IgG(2), known as proline-rich polypeptide complex (PRP), have been
discovered for the first time in ovine colostrum. In this report we present new
data showing that some immunoregulatory peptides associated with the main
immunoglobulin class, IgY, are also present in the avian immune system. Cytokine
inducing activity of particular fractions obtained from ovine colostrum, IgG+
(IgG(2) containing PRP), IgG- (IgG(2) free of PRP), and purified PRP, was
compared with that of crude egg yolk IgY (IgY+), additionally purified egg yolk
IgY (IgY-), and polypeptides accompanying IgY named Yolkin (Y), using an ex vivo
model of whole human blood cells. It was shown that both IgG+ fraction and PRP,
but not IgG-, stimulated the whole blood cells to release tumor necrosis factor
alpha and interleukin-1beta cytokines. Similar experiments performed with hen's
egg IgY preparations showed that IgY+ and Y samples showed higher cytokine
inducing activity than samples additionally purified with the use of size
exclusion chromatography (IgY-). The IgY+ at a dose of 100 MUg was even more
active than the positive lipopolysaccharide control. It was also found that Y is
able to stimulate macrophage cell line J774.2 to release nitric oxide. The
results obtained suggest that IgY, the main chicken immunoglobulin fraction, is
accompanied by additional polypeptides and plays a role of a transporter of
biologically active substances, which was observed in the case of colostral IgG.
PMID- 23155019
TI - Effects of feeding regimen, fiber inclusion, and crude protein content of the
diet on performance and egg quality and hatchability of eggs of broiler breeder
hens.
AB - A 12-wk experiment was conducted to study the effects of feeding regimen,
inclusion of a fiber source, and CP content of the diet on performance of broiler
breeder hens. In total, 360 hens and 60 males, 43 wk of age, were assigned to 60
floor pens (6 hens and 1 male each). There were 12 treatments arranged
factorially with 2 feeding regimens [restricted (R) and liberal feeding (close to
ad libitum consumption; LIB)], 3 sources of fiber (0, 3% inulin, and 3%
cellulose), and 2 levels of CP (14.5 and 17.4%). No interactions among main
effects were observed for any of the traits studied, and therefore, only main
effects are presented. Body weight, liver weight, and abdominal fat weight were
higher (P < 0.001) for the LIB than for the R-fed hens. However, egg production
(P < 0.001), fertility index (P < 0.05), and percentage of hatch (P < 0.01) were
lower for LIB than for R hens. The weights of ovaries (P < 0.05) and the size of
the first preovulatory follicle (P < 0.05) were higher for the LIB than for the R
hens. Also, egg yolk, egg weight, and BW of the hatching chicks were higher (P <
0.001) for the LIB hens. The inclusion of a fiber source in the diet decreased (P
< 0.05) feed intake, BW gain, absolute liver and abdominal fat weight, and egg
yolk weight, with effects being more pronounced (P < 0.05) with cellulose than
with inulin. Hens fed additional fiber produced more (P < 0.05) eggs that were
more fertile (P < 0.05) than control hens. Crude protein content of the diet did
not affect hen performance but reduced (P < 0.01) the relative weight of the
liver, ovary, and abdominal fat. It is concluded that the inclusion of inulin or
cellulose in the diet improved hen performance and that an increase in dietary CP
reduced obesity in broiler breeder hens.
PMID- 23155020
TI - Dietary fibers and crude protein content alleviate hepatic fat deposition and
obesity in broiler breeder hens.
AB - The effects of inclusion of cellulose or inulin as a source of dietary fiber and
CP content of the diet on hepatic fat deposition were investigated in hens fed
restricted or close to ad libitum consumption. There were 12 dietary treatments
forming a 2 * 3 * 2 factorial with 2 feeding regimens [restricted and liberal
(close to ad libitum consumption; LIB)], 3 fiber sources (control, 3% inulin, and
3% cellulose), and 2 levels of CP (14.5 and 17.4%). Hens were assigned in groups
of 6 to 60 floor pens. From 43 to 55 wk of age, hens fed LIB showed increased
activity of the hepatic malic enzyme (MalE; P < 0.01), which led to an increase
(P < 0.001) in liver weight and hepatic lipid deposition and was associated with
enhancements (P < 0.05) in plasma levels of glucose, triglyceride, total
cholesterol, and low-density lipoprotein cholesterol. Abdominal fat deposition
and BW of the hens increased (P < 0.001) with liberal feeding. Inclusion of
inulin in the diet reduced (P < 0.05) liver and abdominal fat weight, whereas
cellulose inclusion decreased (P < 0.05) feed intake, abdominal fat, and BW. An
increase in CP content of the diet from 14.5 to 17.4% reduced MalE activity (P <
0.001), liver weight (P < 0.001), and the accumulation of lipids and cholesterol
in the liver, as well as plasma triglyceride concentration and abdominal fat pad
weight (P < 0.05). It is concluded that fiber inclusion reduced abdominal fat and
liver weight, with effects being more pronounced with cellulose than with inulin.
An increase in dietary CP reduced MalE activity and alleviated hepatic and plasma
lipid concentration; therefore, it might be a practical approach to reduce the
incidence of obesity-linked problems in broiler breeder hens. The combination of
high-CP diets and the inclusion of a fiber source did not suppress liver lipid
content over that observed with the high-CP diet, exclusively.
PMID- 23155021
TI - Bioavailability of organic and inorganic zinc sources in male broilers.
AB - The objective of the current study was to determine the bioavailability of an
organic zinc source (Availa-Zn) compared with zinc sulfate in a European-type
broiler diet. A total of 480 one-day-old male Ross 308 broilers were housed in 48
digestibility cages (10 birds per cage), being randomly divided over 9
treatments. At d 3, the number of birds was standardized to 8. Birds were fed a
basal wheat-maize-soya diet (containing 33.5 mg of Zn/kg) with different
supplementation levels of zinc (reference zinc source: inorganic zinc sulfate: 0,
5, 10, 15, 20, and 40 mg of Zn/kg of feed; test zinc source: Availa-Zn: 0, 5, 10,
15 mg of Zn/kg of feed). Production performance and tibia zinc content were
measured. There were no differences in production performance between the
different zinc sources when fed to broilers until 21 d of age. Tibia zinc content
was increased linearly with the dietary zinc content up to 20 mg/kg zinc sulfate.
The relative biological value of organic zinc was 1.64 compared with zinc sulfate
as a reference zinc source (1.00), as indicated by the slope ratio of the linear
response curves for both zinc sources, using tibia zinc content as a response
parameter. In a practical European broiler diet, the organic Availa-Zn had a
higher bioavailability than inorganic zinc sulfate.
PMID- 23155022
TI - Evaluation of probiotic strains for development of fermented Alisma canaliculatum
and their effects on broiler chickens.
AB - The present study was conducted to select appropriate microbial strains for the
development of fermented Alisma canaliculatum A. Br. et Bouche (FAC) feed
additive and to examine their effects on broilers. In experiment 1, 16 strains of
Lactobacillus acidophilus, Lactobacillus plantarum, Enterococcus faecium,
Bacillus subtilis, Bacillus coagulans, and Saccharomyces cerevisiae from the
Korean Collection for Type Cultures (KCTC) were evaluated. The strains were
tested for their acid, bile, and heat tolerance levels. Among them, L.
acidophilus KCTC 3111, E. faecium KCTC 2022, B. subtilis KCTC 3239, and S.
cerevisiae KCTC 7928 were selected to produce FAC. For experiment 2, 140 Ross
broiler chicks were allocated to four 5-wk-long dietary groups: NC (basal diet),
PC (basal diet with 0.005% oxytetracycline), AC (basal diet with 0.5% A.
canaliculatum rhizome powder), and FAC (basal diet with 0.5% FAC). Final BW and
total BW gain were increased (P < 0.05) upon the addition of FAC, whereas feed
conversion ratio improved (P < 0.05) in the supplemented groups compared with the
NC group. Crude protein content increased and crude fat decreased (P < 0.05) in
the breast meat of the FAC group compared with the AC and PC groups,
respectively. Proventriculus and kidney relative weights of the FAC group
differed (P < 0.05) from the AC group but not from the PC group. Lower (P < 0.05)
thiobarbituric acid reactive substances value of thigh meat was observed in the
FAC group compared with the other groups. The FAC diet increased (P < 0.05) alpha
linolenic acid and linoleic acid in meat. Alteration of these fatty acids led to
increased levels of polyunsaturated fatty acid, polyunsaturated fatty acid
/saturated fatty acid, n-3 and n-6 fatty acids, and decreased n-6/n-3 ratio in
breast or thigh meat (P < 0.05). It is concluded that FAC confers high tolerance
to acid, bile and heat; and beneficially affects growth, meat composition,
oxidative stability, and fatty acid composition. The FAC may be a functional feed
additive in broilers.
PMID- 23155023
TI - Effects of oligosaccharides in a soybean meal-based diet on fermentative and
immune responses in broiler chicks challenged with Eimeria acervulina.
AB - Fermentable oligosaccharides, particularly those found in soybean meal (SBM), may
modulate fermentation in the ceca, thus affecting intestinal immune responses to
intestinal pathogens. We hypothesized that fermentable oligosaccharides found in
SBM would positively affect cecal fermentation and intestinal immune status in
chicks challenged with an acute coccidiosis (Eimeria acervulina) infection and
fed either a SBM-based diet or a semi-purified soy protein isolate- (SPI) based
diet. Using a completely randomized design, 1-d-old broiler chicks (n = 200; 5
replications/treatment; 5 chicks/replication) were assigned to 1 of 4 SBM- or SPI
based diets containing either dietary cellulose (4%) or a fermentable
carbohydrate, galactoglucomannan oligosaccharide-arabinoxylan (GGMO-AX) complex
(4%). On d 9 posthatch, an equal number of chicks on each diet were inoculated
with either distilled water (sham control) or E. acervulina (1 * 10(6) oocysts)
and then euthanized on d 7 postinoculation. Overall, body weight gain and feed
intake were greater (P < 0.01) for SBM-fed chicks, regardless of infection
status. Gain:feed ratio was greater (P <= 0.05) for SPI-fed chicks except during
d 3-7 postinoculation. Infection status, but not fiber source, affected
propionate, isobutyrate, isovalerate, and total branched-chain fatty acid
concentrations (P <= 0.02). Soybean meal-based diets resulted in greater (P <=
0.04) short-chain fatty acid and branched-chain fatty acid concentrations than
SPI-based diets. Messenger RNA fold changes relative to uninfected SBM-cellulose
fed chicks of all duodenal cytokines were greater (P <= 0.01) for infected
chicks, and SBM-fed chicks had greater (P < 0.01) interferon-gamma and
interleukin-12beta expression compared with SPI-fed chicks. Cecal tonsil cytokine
expression was also affected (P <= 0.02) by infection; however, protein source
only affected (P < 0.01) interleukin-1beta expression in this tissue. Overall, a
SBM-based diet, compared with a semi-purified SPI-based diet with a different
ingredient composition, resulted in greater weight gain, feed intake, and short
chain fatty acid production regardless of infection status, and also greater
duodenal cytokine expression in E. acervulina- infected chicks, which is
hypothesized to be related to the nutrients and oligosaccharides found in SBM.
PMID- 23155024
TI - Comparison of amino acid digestibility coefficients for corn, corn gluten meal,
and corn distillers dried grains with solubles among 3 different bioassays.
AB - The objective of this study was to determine standardized AA digestibility of
corn, corn gluten meal, and 3 distillers dried grains with solubles (DDGS) using
the precision-fed cecectomized rooster assay (PFR), the standardized ileal AA
broiler chicken assay (SIAAD), and a newly developed precision-fed ileal broiler
chicken assay (PFC). For the PFR, cecectomized roosters were precision-fed
approximately 30 g of feed sample, and excreta were collected 48 h postfeeding.
For the SIAAD, 16-d-old broilers were ad libitum fed a semi-purified diet
containing the feed samples as the sole source of protein from 17 to 21 d, with
ileal digesta collected at 21 d. For the PFC, 22-d-old broiler chickens were
precision-fed 10 g of feed and ileal digesta were collected at 4 h postfeeding.
For corn, the PFC yielded significantly higher digestibilities than the SIAAD and
PFR for several AA. For corn gluten meal, the PFR yielded significantly higher
values than the PFC for the majority of the AA, with the SIAAD yielding
intermediate values. When 3 DDGS samples were evaluated, the PFR produced higher
digestibilities than the PFC for all 3 DDGS samples for most of the AA. When
comparing the PFR and the SIAAD, the PFR yielded higher values than the SIAAD for
one DDGS, whereas there was generally no significant difference between these 2
methods for the other 2 DDGS samples. The results of this study indicate there
were differences among standardized AA digestibility values for the PFR, SIAAD,
and PFC in some instances. The differences among methods were not consistent;
however, the PFR yielded higher digestibility values than the PFC for 4 of the 5
ingredient samples.
PMID- 23155025
TI - Commercially available amino acid supplementation of low-protein diets for
broiler chickens with different ratios of digestible glycine+serine:lysine.
AB - This work studied the effect of supplementing commercially available amino acids
in low-protein diets using different ratios of digestible (dig)
glycine+serine:lysine (Gly+Ser:Lys) on performance, serum parameters, feathering,
and litter characteristics of broiler chickens during the starter period. A total
of one thousand fifty 1-d-old Cobb-Vantress male chicks were distributed in a
completely randomized experimental design into 6 treatments with 5 replicates of
35 birds each. The treatments were as follows: T1, control diet based on corn and
soybean meal formulated with 22% CP (dig Gly+Ser:Lys ratio of 147); T2, diet with
a 2% CP reduction, supplemented with Val (dig Gly+Ser:Lys ratio of 137); T3,
similar to T2 with the addition of Gly (dig Gly+Ser:Lys ratio of 147); T4, diet
with a 3% CP reduction, supplemented with Val, Ile, and Arg (dig Gly+Ser:Lys
ratio of 127); and T5 and T6, similar to T4 with the addition of Gly (dig
Gly+Ser:Lys ratios of 137 and 147, respectively). At 7 and 21 d, broilers that
had received diets with a 3% CP reduction (19% CP) and a Gly+Ser:Lys ratio that
was equivalent to 127 had lower G:F (P < 0.05) and lower total protein and
albumin serum concentrations (P < 0.05) than those broilers that received the
control feed. However, these parameters were restored to the same level as the
control diet with an increase in the dig Gly+Ser:Lys ratio from 127 to 137 and
147. Diets with a 3% CP reduction (19% CP) resulted in litter with reduced (P <
0.05) nitrogen content and lower ammonia emission than the litter of broilers
receiving the control diet. The treatments did not influence (P > 0.05) the
feather length or feathering scores at 21 or 28 d of age. The supplementation of
essential amino acids while maintaining dig Gly+Ser:Lys ratios at and above 137
allowed for a reduction in the dietary CP of 3% without undermining the
performance, feathering or serum parameters of early stage broilers.
PMID- 23155026
TI - Effects of energy concentration of the diet on productive performance and egg
quality of brown egg-laying hens differing in initial body weight.
AB - The influence of AME(n) concentration of the diet on productive performance and
egg quality traits was studied in Hy-Line brown egg-laying hens differing in
initial BW from 24 to 59 wk of age. Eight treatments were arranged factorially
with 4 diets varying in energy content (2,650, 2,750, 2,850, and 2,950 kcal of
AME(n)/kg) and 2 initial BW of the hens (1,733 vs. 1,606 g). Each treatment was
replicated 5 times (13 hens per replicate), and all diets had similar nutrient
content per unit of energy. No interactions between energy content of the diet
and initial BW of the hens were detected for any trait. An increase in energy
concentration of the diet increased (linear, P < 0.05; quadratic P < 0.05) egg
production, egg mass, energy efficiency (kcal of AME(n)/g of egg), and BW gain (P
< 0.05) but decreased ADFI (linear, P < 0.001) and feed conversion ratio per
kilogram of eggs (linear, P < 0.01; quadratic P < 0.01). An increase in energy
content of the diet reduced Haugh units and the proportion of shell in the egg (P
< 0.01). Feed intake (114.6 vs. 111.1 g/hen per day), AME(n) intake (321 vs. 311
kcal/hen per day), egg weight (64.2 vs. 63.0 g), and egg mass (58.5 vs. 57.0 g)
were higher for the heavier than for the lighter hens (P < 0.01), but feed
conversion ratio per kilogram of eggs and energy efficiency were not affected.
Eggs from the heavier hens had a higher proportion of yolk and lower proportion
of albumen (P < 0.01) and shell (P < 0.05) than eggs from the lighter hens.
Consequently, the yolk-to-albumen ratio was higher (P < 0.001) for the heavier
hens. It is concluded that brown egg-laying hens respond with increases in egg
production and egg mass to increases in AME(n) concentration of the diet up to
2,850 kcal/kg. Heavy hens had higher feed intake and produced heavier eggs and
more egg mass than light hens. However, feed and energy efficiency were better
for the lighter hens.
PMID- 23155027
TI - Gene pathways and cell cycle-related genes in cultured avian primordial germ
cells.
AB - Primordial germ cells (PGC) from early embryos are applicable to various kinds of
research, including the production of transgenic animals. Primordial germ cells
eventually migrate and differentiate into germ cells in the gonads, where they
settle and rapidly proliferate. However, the proliferation rate of PGC is low in
early embryos, and there are many significant pathways that mediate PGC activity.
Therefore, in vitro culture of PGC from early embryos with efficient growth
factors has been necessary. Recently, we cultured chicken PGC from embryonic d
2.5 with basic fibroblast growth factor and characterized the PGC through
analysis of cell morphology, survival, proliferation, and apoptosis. However,
large-scale analyses of genes expressed in cultured PGC and the genes involved in
associated pathways are limited. The objective of the present investigation was
to identify the signaling and metabolic pathways of expressed genes by microarray
comparison between PGC and their somatic counterpart, chicken embryonic
fibroblasts (CEF). We identified 795 genes that were expressed more predominantly
in PGC and 824 genes that were expressed more predominantly in CEF. Among the
predominant genes in PGC, 201 were differentially identified in 106 pathways.
Among the predominant genes in CEF, 242 were differentially identified in 99
pathways. To further validate the genes involved in at least one candidate
pathway, those involved in the cell cycle (12 predominant genes in PGC and 8
predominant genes in CEF) were examined by real-time PCR. To the best of our
knowledge, this study is the first to investigate signaling and metabolic
pathways in cultured PGC.
PMID- 23155028
TI - Feed restriction delays developmental fast skeletal muscle myosin heavy chain
isoforms in turkey poults selected for differential growth.
AB - Genetic selection has been very successful at significantly increasing BW and
breast muscle proportion in commercial broiler and turkey strains. The mechanisms
of breast muscle growth in poultry and the interactive effects of nutritional
status and selection are not fully understood. The hypothesis underlying the
current study is that feed restriction, simply as a vehicle for controlling early
growth, would delay the temporal expression pattern of neonatal (nMyHC) and adult
(aMyHC) fast skeletal muscle myosin heavy chain (MyHC) isoforms in the pectoralis
major muscle of turkey poults. The poultry growth model used to evaluate this
hypothesis consisted of a randombred control turkey line (RBC2) that represents
commercial turkeys of the 1960s and a line developed from the RBC2 by selection
for BW at 16 wk of age (F line). The F line has significantly heavier breast
muscles than the RBC2 concomitant with increased BW, but the proportion of breast
muscle relative to BW is similar. A quantitative indirect ELISA using fast
skeletal MyHC isoform specific monoclonal antibodies revealed no significant line
differences in the temporal expression of posthatch fast skeletal muscle MyHC in
ad libitum fed poults. Feed restriction, however, altered the temporal expression
patterns of nMyHC and aMyHC in both F line and RBC2 poults compared with the
poults fed ad libitum.
PMID- 23155029
TI - Microarray analysis revealed that immunity-associated genes are primarily
regulated by roxarsone in promoting broiler chicken (Gallus gallus domesticus)
growth.
AB - Addition of roxarsone can significantly improve the growth of broiler chickens
(Gallus gallus domesticus). Nevertheless, this application will lead to the
contamination of the environment as well as animal products. Understanding the
response of genes to roxarsone may bring about the discovery of new, safer
substitutes. In this study, we monitored the expression of 8,935 genes in chicken
breast muscle using microarrays. Analysis showed that 30 genes, such as the
interleukin 3 regulated nuclear factor (NFIL3), the regulatory factor X
associated ankyrin-containing protein (RFXANK), the cleavage and polyadenylation
specific factor 3 (CPSF3), and the FK506 binding protein 9 (FKBP9), have
consistently up or downregulated (fold change >=1.5 or <=0.6, P < 0.05, false
discovery rate <=0.05) throughout the medication periods. The results from
microarray analysis were validated by real-time quantitative PCR. Further
functional investigation showed that 13 of the identified genes are well
documented, and surprisingly, 11 (85%) of these are related to immunity (5 are
immunity and defense related, 4 are immunodeficiency disease related, 2 are
immunosuppressive drug related), and the remaining 2 are energy metabolism
related. These findings may suggest that supplement of roxarsone can improve the
immunity of chickens through regulating the expression of associated genes, and
as a result contribute to the growth promotion. Further research on the encoded
proteins of the differentially expressed genes should provide more evidence for
the potential mechanism.
PMID- 23155030
TI - Hypoxic level and duration differentially affect embryonic organ system
development of the chicken (Gallus gallus).
AB - Hypoxia inhibits avian embryonic development, as well as increases embryonic
mortality. However, the key organ systems affected by hypoxia, and their critical
windows for development, are poorly understood. Consequently, chicken embryos
were continuously exposed to 3 levels of oxygen (21, 15, or 13% O(2)) throughout
d 0 to 10, d 11 to 18, or d 0 to 18 of incubation, followed by morphometric and
blood physiological measurements. Hypoxia occurring early during incubation (d 0
to 10) had larger effects on embryonic mortality and organ growth than hypoxia
occurring at later stages (d 10 to 18). Growth of the heart and chorioallantoic
membrane was stimulated by chronic hypoxia, whereas the lung, brain, eye, liver,
stomach, beak, and toes showed no disruption. Sustained hypoxia from the
beginning of incubation decreased blood hemoglobin, hematocrit, and red blood
cell concentration of embryos at d 10, but the values among hypoxic and normoxic
groups were not significantly different at d 18. Blood partial pressure of O(2)
and partial pressure of CO(2) were dependent upon incubation O(2) level at a
given day of development. These results indicated that either modest hypoxia (15%
O(2)) throughout development, or hypoxia at any level during the late stages (d
11 to 18), increased the heart and chorioallantoic membrane weight, which partly
compensated for the detrimental effects of hypoxia on embryonic development. We
conclude that the first half of embryonic development contained the critical
windows for the detrimental effects of hypoxia, and the second half contained the
critical windows for the compensatory response of hypoxia in key organs.
PMID- 23155031
TI - Adhesion and invasion to duck embryo fibroblast cells by Riemerella
anatipestifer.
AB - Here, we investigated adhesion and invasion of Riemerella anatipestifer (RA) to
primary duck embryo fibroblast (DEF) cells. The ability of RA to adhere to, and
more importantly, to invade DEF cells was demonstrated by using a gentamicin
invasion assay and was confirmed by transmission electron microscopy (TEM).
Adhesion of RA could be found by TEM after 1 h of inoculation. Both apoptosis and
necrocytosis of DEF were indicated by TEM after 10 h of incubation, which
suggested a complex mechanism of DEF cell death induced by RA. Our results showed
that internalized RA had the ability to leave the DEF cells. Inhibition studies
indicated that RA proteins play a role in adhesion. Moreover, invasion of RA to
DEF cells was shown to require rearrangement of actin microfilaments and
microtubular cytoskeletal elements. Because the adhesion and invasion ability of
RA to DEF cells could be demonstrated in vitro, similar processes might occur in
vivo, where DEF cells play a crucial role in the diffusion of RA in ducks.
PMID- 23155032
TI - A simple vitrification method for cryobanking avian testicular tissue.
AB - Cryopreservation of testicular tissue is a promising method of preserving male
reproductive potential for avian species. This study was conducted to assess
whether a vitrification method can be used to preserve avian testicular tissue,
using the Japanese quail (Coturnix japonica) as a model. A simple vitrification
method that included dimethyl sulphoxide, ethylene glycol, and sucrose as
cryoprotective agents, and allowed the storage of tissue in a sealed macrotube
was applied to the testicular tissue from 1-wk-old Japanese quail. The vitrified
tissue was warmed at room temperature or at 40 degrees C. After warming, tissue
was implanted onto the chorioallantoic membrane of 8- to 9-d-old chicken embryos
and the vascularization of the grafts was evaluated. When compared with fresh
tissue, the tissue that had been warmed at 40 degrees C showed no difference in
vascularization. The tissue that had been warmed at room temperature was
significantly less vascularized than the fresh tissue. Vitrification of
testicular tissue and storage in macrotubes provide a promising model for
preservation and recovery of male germplasm of avian species.
PMID- 23155033
TI - The effects of low atmosphere stunning and deboning time on broiler breast meat
quality.
AB - Research was conducted to determine the effect of stunning method (low atmosphere
pressure, LAPS, and electrical stunning, ES) and deboning time (0.75 and 4 h) on
breast meat quality (n = 576, 144 birds per treatment) in a commercial processing
plant. Breast meat quality was evaluated through determining pH, Commission
Internationale d'Eclairage L*a*b*, cooking yield, shear force, and consumer
acceptability. The onset of rigor mortis was more rapid (P < 0.05) in breast meat
from LAPS-stunned birds compared with ES-stunned birds, but no differences
existed (P > 0.05) among stunning methods with respect to final pH at 24 h. As
expected, breast meat that was deboned at 4 h required less shear force (P <
0.05) to cut through the breast than samples that were deboned at 0.75 h
postmortem, but no differences existed between breast meat from LAPS or ES
broilers that were deboned at the same time postmortem. However, when samples
were marinated with 2% NaCl and 0.5% phosphate, there was no difference in Allo
Kramer shear force between ES 4 h and LAPS 4-h samples, but the ES 0.75-h samples
had lower shear force values (P < 0.05) than the LAPS 0.75-h samples. On average,
the LAPS 4-h treatment had greater overall acceptability ratings (P < 0.05) than
other treatments, and the ES and LAPS 4-h treatments had more acceptable (P <
0.05) texture than the ES and LAPS 0.75-h treatments. Cluster analysis revealed
that the 2 largest consumer groups liked all chicken breast fillet treatments,
but a larger proportion of consumers liked the 4-h LAPS and ES treatments
compared with the 0.75-h LAPS and ES treatments. In addition, consumers who rated
baked chicken breast as at least moderately acceptable preferred (P < 0.05) the 4
h LAPS samples over the 4-h ES samples. The present study revealed that both the
LAPS and ES systems can be successfully used in commercial poultry plants without
detrimental breast fillet quality problems with respect to color, texture, and
consumer acceptance.
PMID- 23155034
TI - Evaluation of poultry protein isolate as a food ingredient: physicochemical
characteristics of low-fat turkey bologna.
AB - Evaluation of poultry protein isolate (PPI) as a food ingredient was carried out
by substituting nonmeat ingredients such as soy protein isolate (SPI) or meat
protein in turkey bologna. Two concentrations (1.5 and 2% dry weight basis) of
PPI prepared from mechanically separated turkey meat were used in this study. Two
control samples were prepared with 11 and 13% meat protein, respectively.
Physicochemical characteristics of turkey bologna containing PPI were compared
with those of control and SPI-containing samples. Batter strength was higher for
2% PPI and 13% meat protein control samples (control-2) compared with all other
treatments. Cooking yield of the 11% meat protein control was significantly (P <
0.05) less compared with other treatments. However, there was no significant
difference in the expressible moisture or purge loss among all the treatments.
Control-2 showed lower L* values and was more reddish during refrigerated
storage. Addition of protein isolates caused a significant increase (b* value
varied between 11.48 and 12.52) in yellowness of products. Turkey bologna with
added protein isolates showed significantly lower lipid oxidation as indicated by
induced TBA reactive substance analysis. Results from this study suggest that SPI
or meat protein could be replaced by PPI without negatively affecting product
characteristics as evident from cooking yield and purge loss values.
PMID- 23155035
TI - Effect of different levels of dietary vitamin E (DL-alpha-tocopherol acetate) on
the occurrence of various degrees of white striping on broiler breast fillets.
AB - White striping could be a potential reason for the rejection of raw breast
fillets in the market. The condition is characterized grossly by the white
striations occurring on the fillets showing myopathic changes on microscopic
examination. Early research has shown similar lesions in the case of nutritional
muscular dystrophy, which is a condition caused mainly by the deficiency of
vitamin E in the diet. The present study was intended to evaluate the effect of
different levels of dietary vitamin E (dl-alpha-tocopherol acetate) on the
incidence of normal, moderate, and severe degrees of white striping, by modern
description, on broiler breast fillets. Basal diets adequate for starter (0 to 18
d), grower (19 to 32 d), and finisher (33 to 49 d) age periods supplemented with
15, 50, 100, 200, and 400 IU of vitamin E/kg of feed were used in the study. Each
of the 5 diet treatments were fed to 8 pens (53 birds each) of male broilers from
a commercial strain. At 49 d, 5 birds were randomly selected from each pen (n =
40 birds/diet treatment) and were processed. Live weight, ready-to-cook weight,
weight of the fillets, wings, tenders, legs, and the racks were obtained. The
fillets were scored for the 3 degrees of white striping. There were no
significant differences among the diet treatments with respect to the weight and
carcass yield parameters. Furthermore, the diet treatments did not show any
significant effect on the occurrence of normal, moderate, and severe degrees of
white striping. However, fillet weight was the only parameter that had a
significant effect on the occurrence of white striping. Higher degrees of white
striping were seen associated with heavier fillets, which is in accordance with
previous studies. Different levels of vitamin E levels used in the present study
did not show any significant effect on the occurrence of 3 degrees of white
striping. These results suggest that dietary vitamin E level is not associated
with the modern condition of white striping in broiler breast meat.
PMID- 23155036
TI - Effects of increasing concentrations of corn distillers dried grains with
solubles on the egg production and internal quality of eggs.
AB - A study was conducted to determine the effect of feeding high concentrations of
corn distillers dried grains with solubles (DDGS) on egg production and the
internal quality of eggs from laying hens. Four diets were formulated to contain
0, 17, 35, or 50% corn DDGS. A total of two hundred forty 54-wk-old Single-Comb
White Leghorn laying hens were randomly allotted to 2 birds per cage with 3
consecutive cages representing an experimental unit (EU). Each EU was assigned to
1 of 4 dietary treatments according to a completely randomized design. Hens were
fed for a 24-wk experimental period after transition feeding to gradually
increase corn DDGS inclusion over a 4-wk period. Two sets of experimental diets
were formulated, and each diet was fed for 12 wk. Egg production, feed
consumption, egg component, yolk color, Haugh unit during storage times, and
shell breaking strength were measured. Egg production, egg weight, egg mass, feed
intake, and feed efficiency were adversely affected by the highest level of DDGS
in the diet (50%) during the first 12-wk period. Once diets were reformulated to
include an increased concentration of both lysine and methionine, differences
among the dietary treatments were reduced, as the performance of the 50% DDGS
diets was greatly improved. Over the last 6 wk of study, no differences in egg
production, egg weight, and feed intake among DDGS treatments were found. The
DDGS diets positively affected the internal quality of eggs during storage.
Improved yolk color and Haugh unit were observed as the dietary DDGS levels
increased, but the increase for Haugh unit was significant only when the DDGS
level was 50%. Shell weight percentage was increased in the 50% DDGS diet, but no
differences in yolk and albumen percentage were observed. It was concluded that
up to 50% of DDGS could be included in the layer's diet without affecting egg
weight, feed intake, egg mass, feed efficiency, and egg production as long as
digestible amino acids were sufficient in DDGS-added diets.
PMID- 23155037
TI - Effect of kosher salt application on microbial profiles of poultry carcasses.
AB - The effect of conventionally applied kosher salt on the microbiological profile
of posteviscerated chicken carcasses obtained from a local commercial processing
facility was evaluated. The broiler carcasses were divided into treatments 1
through 8. Standard sampling methods were used to evaluate Salmonella prevalence,
aerobic plate counts, coliforms, generic Escherichia coli, and psychrotroph
counts. Results indicate significant reductions in microbial populations in all
the salted groups compared with controls. Significant reductions (1.45, 2.31,
2.81, and 1.48 log cfu/mL of rinse) were obtained for aerobic plate count (APC),
coliforms, generic E. coli, and psychrotroph counts, respectively, on prechill
salt-treated carcasses compared with controls. Salt-treated carcasses sampled
after chilling had lower microbial populations compared with control chilled
samples with significant reductions in coliforms and generic E. coli (1.25 and
1.77 log, respectively). Salt-treated samples had lower counts on APC and
psychrotrophs after 10 d of refrigerated storage compared with controls. Finally,
drip loss of salt-treated carcasses was lower after 24 h compared with nontreated
controls. Based on the results, it can be concluded that salting process is an
effective contributor to microbial reductions during processing that needs
further investigation as a possible intervention in commercial poultry processing
settings.
PMID- 23155038
TI - Modified-atmosphere packaging of hen table eggs: effects on pathogen and spoilage
bacteria.
AB - As part of a more comprehensive research activity on the use of modified
atmosphere packaging for the improvement of quality and functional properties of
table eggs, the effects of air, 100% CO(2), and 100% O(2) packaging were also
evaluated on the survival of experimentally inoculated pathogen bacteria
(Salmonella Enteritidis, Escherichia coli, and Listeria monocytogenes) as well as
on spoilage bacteria (total aerobic mesophilic bacteria) on table eggs during 30
d of storage at 4, 25, and 37 degrees C by colony count method. In general,
temperatures played a major role, rather than gasses, in influencing the
bacterial survival. In particular, the lowest microbial loads were registered at
4 degrees C on E. coli and spoilage bacteria, whereas 37 degrees C was the best
storage temperature to avoid the psychrotropic microorganism L. monocytogenes
development regardless of the gas used. One hundred percent CO(2) packaging, in
association with a low storage temperature (4 degrees C), had a significant
positive effect in reducing Salmonella loads. On eggs inoculated with L.
monocytogenes and stored at 4 degrees C as well as on eggs containing only
spoilage bacteria and stored at 25 degrees C, 100% CO(2) resulted the best gas in
comparison with air and O(2). One hundred percent CO(2) packaging showed no
negative effect on pathogen survival compared with air. Although further
improvements are required to control RH within packaging to limit bacteria
growth/survival, in view of the positive effects of CO(2) packaging on quality
traits of table eggs, 100% CO(2) packaging might represent a promising innovative
technique for the maintenance of egg characteristics during transport, retail,
and domestic storage.
PMID- 23155039
TI - Effect of manipulation of incubation temperature on fatty acid profiles and
antioxidant enzyme activities in meat-type chicken embryos.
AB - Eggs (n = 1,800) obtained from Ross broiler breeders at 32 and 48 wk of age were
incubated at either a constant temperature of 37.6 degrees C throughout (T1), or
the temperature was reduced for 6 h to 36.6 degrees C each day during embryonic
age (EA) 10 to 18 (T2). Yolk sac, liver, and brain fatty acid profiles and
oxidant and antioxidant status of liver and brain were measured at EA 14, 19, and
day of hatch (DOH). Fatty acid profiles of yolk sac, liver, and brain were
influenced by age of breeder with significant breeder hen age * incubation
temperature interactions. At EA 14, higher levels of 20:4n-6 and 22:6n-3 had been
transferred from the yolk sac to T2 embryos from younger than older breeders,
whereas for T1 and T2 embryos, yolk sac 20:4n-6 and 22.6n-3 values were similar
for older breeders. Accumulation of 20:4n-6 and 22:6n-3 fatty acids in the liver
of T1 and T2 embryos from younger breeders was similar; however, T2 embryos from
older breeders had higher liver levels of 20:4n-6 and 22:6n-3 than T1 embryos. At
EA 19, liver nitric oxide levels were higher for T2 embryos from younger breeders
than those from breeders incubated at T1. Brain catalase levels of T2 embryos
from younger breeders were higher than those from older breeders at DOH. Thus,
changes in fatty acid profiles and catalase and nitric oxide production of brain
and liver tissues resulting from 1 degrees C lower incubation temperature from EA
10 to 18 reflect adaptive changes.
PMID- 23155040
TI - A model for an economically optimal replacement of a breeder flock.
AB - A deterministic model is developed to support the tactical and operational
replacement decisions at broiler breeder farms. The marginal net revenue approach
is applied to determine the optimal replacement age of a flock. The objective
function of the model maximizes the annual gross margin over the flock's
production cycle. To calculate the gross margin, future egg production,
fertility, or hatchability of the eggs, revenues and variable costs of a flock
were estimated. For tactical decisions, the optimal laying length is the age at
which the average gross margin of an average flock is maximal. For operational
decisions, a flock should be replaced when the marginal gross margin of a
replaceable flock is less than the average gross margin of an average flock. To
demonstrate the model, a broiler breeder flock from a Dutch breeder farm was
used. A sensitivity analysis showed that the optimal replacement decision, for
both tactical and operational management, is sensitive to the decrease in the
weekly egg production after the peak and the prices of feed and hatching eggs.
The effect of the decrease in weekly fertility after the peak on the replacement
decision is related to the payment system for hatching eggs.
PMID- 23155041
TI - Development of artificial neural network models based on experimental data of
response surface methodology to establish the nutritional requirements of
digestible lysine, methionine, and threonine in broiler chicks.
AB - An artificial neural network (ANN) approach was used to develop feed-forward
multilayer perceptron models to estimate the nutritional requirements of
digestible lysine (dLys), methionine (dMet), and threonine (dThr) in broiler
chicks. Sixty data lines representing response of the broiler chicks during 3 to
16 d of age to dietary levels of dLys (0.88-1.32%), dMet (0.42-0.58%), and dThr
(0.53-0.87%) were obtained from literature and used to train the networks. The
prediction values of ANN were compared with those of response surface methodology
to evaluate the fitness of these 2 methods. The models were tested using R(2),
mean absolute deviation, mean absolute percentage error, and absolute average
deviation. The random search algorithm was used to optimize the developed ANN
models to estimate the optimal values of dietary dLys, dMet, and dThr. The ANN
models were used to assess the relative importance of each dietary input on the
bird performance using sensitivity analysis. The statistical evaluations revealed
the higher accuracy of ANN to predict the bird performance compared with response
surface methodology models. The optimization results showed that the maximum BW
gain may be obtained with dietary levels of 1.11, 0.51, and 0.78% of dLys, dMet,
and dThr, respectively. Minimum feed conversion ratio may be achieved with
dietary levels of 1.13, 0.54, 0.78% of dLys, dMet, and dThr, respectively. The
sensitivity analysis on the models indicated that dietary Lys is the most
important variable in the growth performance of the broiler chicks, followed by
dietary Thr and Met. The results of this research revealed that the experimental
data of a response-surface-methodology design could be successfully used to
develop the well-designed ANN for pattern recognition of bird growth and
optimization of nutritional requirements. The comparison between the 2 methods
also showed that the statistical methods may have little effect on the ideal
ratios of dMet and dThr to dLys in broiler chicks using multivariate
optimization.
PMID- 23155042
TI - Predicting body and carcass characteristics of 2 broiler chicken strains using
support vector regression and neural network models.
AB - As a new modeling method, support vector regression (SVR) has been regarded as
the state-of-the-art technique for regression and approximation. In this study,
the SVR models had been introduced and developed to predict body and carcass
related characteristics of 2 strains of broiler chicken. To evaluate the
prediction ability of SVR models, we compared their performance with that of
neural network (NN) models. Evaluation of the prediction accuracy of models was
based on the R(2), MS error, and bias. The variables of interest as model output
were BW, empty BW, carcass, breast, drumstick, thigh, and wing weight in 2
strains of Ross and Cobb chickens based on intake dietary nutrients, including ME
(kcal/bird per week), CP, TSAA, and Lys, all as grams per bird per week. A data
set composed of 64 measurements taken from each strain were used for this
analysis, where 44 data lines were used for model training, whereas the remaining
20 lines were used to test the created models. The results of this study revealed
that it is possible to satisfactorily estimate the BW and carcass parts of the
broiler chickens via their dietary nutrient intake. Through statistical criteria
used to evaluate the performance of the SVR and NN models, the overall results
demonstrate that the discussed models can be effective for accurate prediction of
the body and carcass-related characteristics investigated here. However, the SVR
method achieved better accuracy and generalization than the NN method. This
indicates that the new data mining technique (SVR model) can be used as an
alternative modeling tool for NN models. However, further reevaluation of this
algorithm in the future is suggested.
PMID- 23155043
TI - Assessment of production performance in 2 breeds of broilers fed prebiotics as
feed additives.
AB - Pasture-flock-raised poultry are becoming an increasingly popular product, but
only limited options are currently available for maintaining gut health. For
these producers, prebiotics are an attractive option because they are generally
recognized as safe (GRAS) and can be mixed into the feed and thus do not require
adjustments to production protocols. However, if prebiotic treatments reduce
production performance, they would not be useful to producers. Thus, the
objective of this study was to measure performance of pasture-raised broilers fed
1 of 3 prebiotic treatments. For these trials, 2 breeds of birds were used: Naked
Neck slow-growing breeds and Cornish White Rock cross fast-growing breeds. The
experimental design was replicated for each breed. A total of 340 birds were
split into 4 groups, each group fed one feed additive: 1) galactoligosaccharides
(2% wt/wt), 2) fructooligosaccharides (1% wt/wt), 3) plum fibers (1% wt/wt), or
4) no additives. During the 8-wk rearing period, 10 birds from each group were
collected and euthanized to take small intestine samples. Histological
preparations were made from the small intestine tissue, and 4 measurements of
villi height and crypt depth from each cross section were taken. Throughout the
study, mortality was monitored and BW measurements were taken at 2-wk intervals.
For the Cornish White Rock cross, the group receiving the feed supplemented with
fructooligosaccharides had higher (P < 0.05) 8-wk BW than those fed Plum; control
and birds fed galactoligosaccharides were intermediate. For the Naked Neck breed,
the group receiving the plum fibers had the highest final BW. It appears that all
3 feed supplements offered some protective effect for alterations in villi length
and crypt depth due to feed withdrawal, but only for the Naked Neck breed. The
data indicate the 3 prebiotics utilized in this study could be used without risk
of decreasing production performance, but only for Naked Neck breeds.
PMID- 23155044
TI - Oncogenic Wnt/beta-catenin signalling pathways in the cancer-resistant epididymis
have implications for cancer research.
AB - Aberrant activation of the Wnt/beta-catenin pathway occurs in cancers. This
review presents several important cancer-related aspects of Wnt/beta-catenin
signalling relevant to the epididymis, provides evidence of such epididymal gene
expression and suggests a new direction for further research. The data presented
here indicate that besides containing many Wnt/beta-catenin-pathway components,
the normal adult human epididymis expresses much more beta-catenin than the
colorectal carcinoma cell line HCT116, which possesses elevated beta-catenin
expression. The low cancer incidence in the epididymis may be due to factors
present in the human epididymis that regulate this oncogenic Wnt/beta-catenin
pathway, including (i) 14 of 17 secreted pathway inhibitors, (ii) the majority of
the micro-RNAs known to target this pathway, (iii) plasma membrane-associated E
cadherin and CEACAM1 that anchor beta-catenin, preventing its availability for
nuclear entry and oncogenic transcriptional activity, (iv) the recently
identified membrane-located tumourigenesis inhibitors RNF43 and ZNRF3 that
mediate the degradation of the Wnt receptor components Fzds and Lrp5/6 and (v)
nuclear KLF4, which competes with TCF for beta-catenin, limiting its
transcriptional activity and stabilizing telomeres, thereby reducing mutation
incidence. The above regulatory factors expressed by the human epididymis, and
the absence of androgen receptor translocation known to promote nuclear
translocation of beta-catenin in tumourigenesis in an animal model, may act
synergistically to provide hostility in different cell compartments towards
tumour formation. The lack of evidence for beta-catenin in epididymal nuclei is
noteworthy. Studying this phenomenon may help reveal the mechanisms underlying
oncogenic Wnt/beta-catenin signalling and shed new light on cancer therapy and
prevention.
PMID- 23155045
TI - Diverse roles of strigolactones in plant development.
AB - With the discovery of strigolactones as root exudate signals that trigger
parasitic weed seed germination, and then as a branching inhibitor and plant
hormone, the next phase of strigolactone research has quickly revealed this
hormone class as a major player in optimizing plant growth and development. From
the early stages of plant evolution, it seems that strigolactones were involved
in enabling plants to modify growth in order to gain advantage in competition
with neighboring organisms for limited resources. For example, a moss plant can
alter its growth in response to strigolactones emanating from a neighbor. Within
a higher plant, strigolactones appear to be involved in controlling the balance
of resource distribution via strategic modification of growth and development.
Most notably, higher plants that encounter phosphate deficiency increase
strigolactone production, which changes root growth and promotes fungal symbiosis
to enhance phosphate intake. The shoot also changes by channeling resources away
from unessential leaves and branches and into the main stem and root system. This
hormonal response is a key adaption that radically alters whole-plant
architecture in order to optimize growth and development under diverse
environmental conditions.
PMID- 23155046
TI - Characterization of a small molecule inhibitor of plasminogen activator inhibitor
type 1 that accelerates the transition into the latent conformation.
AB - A novel class of small molecule inhibitors for plasminogen activator inhibitor
type 1 (PAI-1), represented by AZ3976, was identified in a high throughput
screening campaign. AZ3976 displayed an IC(50) value of 26 MUm in an enzymatic
chromogenic assay. In a plasma clot lysis assay, the compound was active with an
IC(50) of 16 MUm. Surprisingly, AZ3976 did not bind to active PAI-1 but bound to
latent PAI-1 with a K(D) of 0.29 MUm at 35 degrees C and a binding stoichiometry
of 0.94, as measured by isothermal calorimetry. Reversible binding was confirmed
by surface plasmon resonance direct binding experiments. The x-ray structure of
AZ3976 in complex with latent PAI-1 was determined at 2.4 A resolution. The
inhibitor was bound in the flexible joint region with the entrance to the cavity
located between alpha-helix D and beta-strand 2A. A set of surface plasmon
resonance experiments revealed that AZ3976 inhibited PAI-1 by enhancing the
latency transition of active PAI-1. Because AZ3976 only had measurable affinity
for latent PAI-1, we propose that its mechanism of inhibition is based on binding
to a small fraction in equilibrium with active PAI-1, a latent-like prelatent
form, from which latent PAI-1 is then generated more rapidly. This mode of
action, with induced accelerated latency transition of active PAI-1 may, together
with supporting x-ray data, provide improved opportunities for small molecule
drug design in the hunt for therapeutically useful PAI-1 inhibitors.
PMID- 23155047
TI - Exposure to a cutinase-like serine esterase triggers rapid lysis of multiple
mycobacterial species.
AB - Mycobacteria are shaped by a thick envelope made of an array of uniquely
structured lipids and polysaccharides. However, the spatial organization of these
molecules remains unclear. Here, we show that exposure to an esterase from
Mycobacterium smegmatis (Msmeg_1529), hydrolyzing the ester linkage of trehalose
dimycolate in vitro, triggers rapid and efficient lysis of Mycobacterium
tuberculosis, Mycobacterium bovis BCG, and Mycobacterium marinum. Exposure to the
esterase immediately releases free mycolic acids, while concomitantly depleting
trehalose mycolates. Moreover, lysis could be competitively inhibited by an
excess of purified trehalose dimycolate and was abolished by a S124A mutation
affecting the catalytic activity of the esterase. These findings are consistent
with an indispensable structural role of trehalose mycolates in the architectural
design of the exposed surface of the mycobacterial envelope. Importantly, we also
demonstrate that the esterase-mediated rapid lysis of M. tuberculosis
significantly improves its detection in paucibacillary samples.
PMID- 23155048
TI - Mechanical modulation of ATP-binding affinity of V1-ATPase.
AB - V(1)-ATPase is a rotary motor protein that rotates the central shaft in a
counterclockwise direction hydrolyzing ATP. Although the ATP-binding process is
suggested to be the most critical reaction step for torque generation in F(1)
ATPase (the closest relative of V(1)-ATPase evolutionarily), the role of ATP
binding for V(1)-ATPase in torque generation has remained unclear. In the present
study, we performed single-molecule manipulation experiments on V(1)-ATPase from
Thermus thermophilus to investigate how the ATP-binding process is modulated upon
rotation of the rotary shaft. When V(1)-ATPase showed an ATP-waiting pause, it
was stalled at a target angle and then released. Based on the response of the
V(1)-ATPase released, the ATP-binding probability was determined at individual
stall angles. It was observed that the rate constant of ATP binding (k(on)) was
exponentially accelerated with forward rotation, whereas the rate constant of ATP
release (k(off)) was exponentially reduced. The angle dependence of the k(off) of
V(1)-ATPase was significantly smaller than that of F(1)-ATPase, suggesting that
the ATP-binding process is not the major torque-generating step in V(1)-ATPase.
When V(1)-ATPase was stalled at the mean binding angle to restrict rotary
Brownian motion, k(on) was evidently slower than that determined from free
rotation, showing the reaction rate enhancement by conformational fluctuation. It
was also suggested that shaft of V(1)-ATPase should be rotated at least 277
degrees in a clockwise direction for efficient release of ATP under ATP
synthesis conditions.
PMID- 23155049
TI - Inhibition of glycogen synthase kinase-3 ameliorates beta-amyloid pathology and
restores lysosomal acidification and mammalian target of rapamycin activity in
the Alzheimer disease mouse model: in vivo and in vitro studies.
AB - Accumulation of beta-amyloid (Abeta) deposits is a primary pathological feature
of Alzheimer disease that is correlated with neurotoxicity and cognitive decline.
The role of glycogen synthase kinase-3 (GSK-3) in Alzheimer disease pathogenesis
has been debated. To study the role of GSK-3 in Abeta pathology, we used 5XFAD
mice co-expressing mutated amyloid precursor protein and presenilin-1 that
develop massive cerebral Abeta loads. Both GSK-3 isozymes (alpha/beta) were
hyperactive in this model. Nasal treatment of 5XFAD mice with a novel substrate
competitive GSK-3 inhibitor, L803-mts, reduced Abeta deposits and ameliorated
cognitive deficits. Analyses of 5XFAD hemi-brain samples indicated that L803-mts
restored the activity of mammalian target of rapamycin (mTOR) and inhibited
autophagy. Lysosomal acidification was impaired in the 5XFAD brains as indicated
by reduced cathepsin D activity and decreased N-glycoyslation of the vacuolar
ATPase subunit V0a1, a modification required for lysosomal acidification.
Treatment with L803-mts restored lysosomal acidification in 5XFAD brains. Studies
in SH-SY5Y cells confirmed that GSK-3alpha and GSK-3beta impair lysosomal
acidification and that treatment with L803-mts enhanced the acidic lysosomal pool
as demonstrated in LysoTracker Red-stained cells. Furthermore, L803-mts restored
impaired lysosomal acidification caused by dysfunctional presenilin-1. We provide
evidence that mTOR is a target activated by GSK-3 but inhibited by impaired
lysosomal acidification and elevation in amyloid precursor protein/Abeta loads.
Taken together, our data indicate that GSK-3 is a player in Abeta pathology.
Inhibition of GSK-3 restores lysosomal acidification that in turn enables
clearance of Abeta burdens and reactivation of mTOR. These changes facilitate
amelioration in cognitive function.
PMID- 23155050
TI - ras-Induced up-regulation of CTP:phosphocholine cytidylyltransferase alpha
contributes to malignant transformation of intestinal epithelial cells.
AB - Cancer cells have enhanced lipogenic capacity characterized by increased
synthesis of fatty acids and complex lipids, including phosphatidylcholine (PC).
As the rate-limiting enzyme in the CDP-choline pathway for PC synthesis,
CTP:phosphocholine cytidylyltransferase alpha (CCTalpha) is implicated in the
provision of membranes and bioactive lipids necessary of cell proliferation. In
this study, we assessed the role of CCTalpha in malignant intestinal epithelial
cells transformed with activated H-ras (IEC-ras). Three IEC-ras clones had
significant up-regulation CCTalpha expression, but PC synthesis and in vitro
activity of CCTalpha were similar to control IEC. RNA interference of CCTalpha in
adherent IEC-ras did not affect PC synthesis, confirming that the enzyme was
relatively inactive. However, CCTalpha silencing in ras-transformed IEC reduced
anchorage-independent growth, a criterion for malignant transformation, as well
as tumorigenicity in mice. Relative to their adherent counterparts, detached IEC
ras had increased PC synthesis that was attenuated by inducible CCTalpha
silencing. Detachment of IEC-ras was accompanied by increased CCTalpha
phosphorylation and cytosolic enzyme activity. We conclude that the expanded pool
of CCTalpha in IEC-ras is activated by detachment. This provides the increased PC
biosynthetic capacity that contributes to malignant transformation of intestinal
epithelial cells when detached from the extracellular matrix.
PMID- 23155051
TI - The retinol dehydrogenase Rdh10 localizes to lipid droplets during acyl ester
biosynthesis.
AB - Rdh10 catalyzes the first step of all-trans-retinoic acid biogenesis
physiologically, conversion of retinol into retinal. We show that Rdh10
associates predominantly with mitochondria/mitochondrial-associated membrane
(MAM) in the absence of lipid droplet biosynthesis, but also locates with lipid
droplets during acyl ester biosynthesis. Targeting to lipid droplets requires the
32 N-terminal residues, which include a hydrophobic region followed by a net
positive charge. Targeting to mitochondria/MAM and/or the stability of Rdh10
require both the N-terminal and the 48 C-terminal hydrophobic residues. Rdh10
behaves similarly to cellular retinol-binding protein, type 1, which also
localizes to mitochondria/MAM before lipid droplet synthesis, and associates with
lipid droplets during acyl ester synthesis (Jiang, W., and Napoli, J. L. (2012)
Biochem. Biophys. Acta 1820, 859-8692). LRAT, an ER protein, also associates with
lipid droplets upon acyl ester biosynthesis. Colocalization of Rdh10, Crbp1, and
LRAT on lipid droplets suggests a metabolon that mediates retinol homeostasis.
PMID- 23155052
TI - Matrix metalloproteinase-1-mediated up-regulation of vascular endothelial growth
factor-2 in endothelial cells.
AB - Matrix metalloproteinase-1 (MMP-1) is a collagenase that is highly active in
extracellular matrix and vascular remodeling, angiogenesis, and tumor
progression. Vascular endothelial growth factor receptor-2 (VEGFR2), the main
receptor for VEGF-A, is expressed on endothelial cells and promotes cell
survival, proliferation, and other functions. Although MMP-1 and VEGFR2 co-exist
in many normal and pathophysiological conditions, the effect of MMP-1 on cellular
VEGFR2 that can promote the above processes is unknown. In this study we test the
hypothesis that stimulation of endothelial cells with MMP-1 increases their
levels of VEGFR2. The increased VEGFR2 is then available to bind VEGF-A,
resulting in increased response. Indeed we found that endothelial cells incubated
with active MMP-1 had higher mRNA and protein levels of VEGFR2. Furthermore, VEGF
A-dependent phosphorylation of intracellular signaling molecules and endothelial
proliferation were elevated after MMP-1 treatment. MMP-1 caused activation of the
nuclear factor-kappaB (NF-kappaB) pathway (p65/RelA) in endothelial cells, and
this response was dependent upon activation of protease activated receptor-1 (PAR
1). Chromatin immunoprecipitation was used to confirm NF-kappaB-mediated active
transcription of the VEGFR2 (KDR) gene. Elevation in VEGFR2 after MMP-1
stimulation was inhibited by PAR-1 knockdown and NF-kappaB specific inhibition.
We conclude that MMP-1 promotes VEGFR2 expression and proliferation of
endothelial cells through stimulation of PAR-1 and activation of NF-kappaB. These
results suggest a mechanism by which MMP-1 may prime or sensitize endothelial
cell functions.
PMID- 23155053
TI - Integration and long distance axonal regeneration in the central nervous system
from transplanted primitive neural stem cells.
AB - Spinal cord injury (SCI) results in devastating motor and sensory deficits
secondary to disrupted neuronal circuits and poor regenerative potential. Efforts
to promote regeneration through cell extrinsic and intrinsic manipulations have
met with limited success. Stem cells represent an as yet unrealized therapy in
SCI. Recently, we identified novel culture methods to induce and maintain
primitive neural stem cells (pNSCs) from human embryonic stem cells. We tested
whether transplanted human pNSCs can integrate into the CNS of the developing
chick neural tube and injured adult rat spinal cord. Following injection of pNSCs
into the developing chick CNS, pNSCs integrated into the dorsal aspects of the
neural tube, forming cell clusters that spontaneously differentiated into
neurons. Furthermore, following transplantation of pNSCs into the lesioned rat
spinal cord, grafted pNSCs survived, differentiated into neurons, and extended
long distance axons through the scar tissue at the graft-host interface and into
the host spinal cord to form terminal-like structures near host spinal neurons.
Together, these findings suggest that pNSCs derived from human embryonic stem
cells differentiate into neuronal cell types with the potential to extend axons
that associate with circuits of the CNS and, more importantly, provide new
insights into CNS integration and axonal regeneration, offering hope for repair
in SCI.
PMID- 23155054
TI - Characterization of the enzyme CbiH60 involved in anaerobic ring contraction of
the cobalamin (vitamin B12) biosynthetic pathway.
AB - The anaerobic pathway for the biosynthesis of cobalamin (vitamin B(12)) has
remained poorly characterized because of the sensitivity of the pathway
intermediates to oxygen and the low activity of enzymes. One of the major
bottlenecks in the anaerobic pathway is the ring contraction step, which has not
been observed previously with a purified enzyme system. The Gram-positive aerobic
bacterium Bacillus megaterium has a complete anaerobic pathway that contains an
unusual ring contraction enzyme, CbiH(60), that harbors a C-terminal extension
with sequence similarity to the nitrite/sulfite reductase family. To improve
solubility, the enzyme was homologously produced in the host B. megaterium
DSM319. CbiH(60) was characterized by electron paramagnetic resonance and shown
to contain a [4Fe-4S] center. Assays with purified recombinant CbiH(60)
demonstrate that the enzyme converts both cobalt-precorrin-3 and cobalt factor
III into the ring-contracted product cobalt-precorrin-4 in high yields, with the
latter transformation dependent upon DTT and an intact Fe-S center. Furthermore,
the ring contraction process was shown not to involve a change in the oxidation
state of the central cobalt ion of the macrocycle.
PMID- 23155056
TI - Structural insights into the stability perturbations induced by N-terminal
variation in human and goat alpha-lactalbumin.
AB - Addition of an extra methionine at the N-terminus by recombinant expression of
alpha-lactalbumin in Escherichia coli significantly destabilizes the protein, and
this destabilization has hampered mutational analyses such as the mutational phi
value analysis of the protein. Deletion of residue 1 from the recombinant form
recovers the stability in human and goat alpha-lactalbumin. Here, we thus
determined the crystal structures of the residue 1-deletion variants of
recombinant human and goat alpha-lactalbumin, and compared the structures with
those of the authentic and recombinant forms. The results demonstrate the
importance of the N-terminal backbone structure and hydrogen-bonding pattern for
the stability of alpha-lactalbumin.
PMID- 23155055
TI - In vivo phosphorylation of Ser21 and Ser83 during nutrient-induced activation of
the yeast protein kinase A (PKA) target trehalase.
AB - The readdition of an essential nutrient to starved, fermenting cells of the yeast
Saccharomyces cerevisiae triggers rapid activation of the protein kinase A (PKA)
pathway. Trehalase is activated 5-10-fold within minutes and has been used as a
convenient reporter for rapid activation of PKA in vivo. Although trehalase can
be phosphorylated and activated by PKA in vitro, demonstration of phosphorylation
during nutrient activation in vivo has been lacking. We now show, using
phosphospecific antibodies, that glucose and nitrogen activation of trehalase in
vivo is associated with phosphorylation of Ser(21) and Ser(83). Unexpectedly,
mutants with reduced PKA activity show constitutive phosphorylation despite
reduced trehalase activation. The same phenotype was observed upon deletion of
the catalytic subunits of yeast protein phosphatase 2A, suggesting that lower PKA
activity causes reduced trehalase dephosphorylation. Hence, phosphorylation of
trehalase in vivo is not sufficient for activation. Deletion of the inhibitor
Dcs1 causes constitutive trehalase activation and phosphorylation. It also
enhances binding of trehalase to the 14-3-3 proteins Bmh1 and Bmh2, suggesting
that Dcs1 inhibits by preventing 14-3-3 binding. Deletion of Bmh1 and Bmh2
eliminates both trehalase activation and phosphorylation. Our results reveal that
trehalase activation in vivo is associated with phosphorylation of typical PKA
sites and thus establish the enzyme as a reliable read-out for nutrient
activation of PKA in vivo.
PMID- 23155057
TI - Engineering of alpha1-antitrypsin variants with improved specificity for the
proprotein convertase furin using site-directed random mutagenesis.
AB - Furin, PACE4, PC5/6 and PC7 are members of the subtilisin-like proprotein
convertase (SPC) family. Although these enzymes are known to play critical roles
in various physiological and pathological events including cell differentiation,
tumor growth, virus replication and the activation of bacterial toxins, their
distinct functions are yet to be fully delineated. alpha1-PDX is an engineered
alpha1-antitrypsin variant carrying the RXXR consensus motif for furin within its
reactive site loop. However, alpha1-PDX inhibits other SPCs in addition to furin.
In this work, we prepared various rat alpha1-antitrypsin variants containing Arg
at the P1 site within the reactive site loop, and examined their respective
selectivity. The novel alpha1-antitrypsin variant AVNR (AVPM(352)/AVNR) was
identified as a highly selective inhibitor of furin. This variant formed a sodium
dodecyl sulfate- and heat-stable furin/alpha1-antitrypsin complex and inhibited
furin activity ex vivo and in vitro. Other SPC members including PACE4, PC5/6 and
PC7 were not inhibited by the AVNR variant. Furin-mediated maturation of bone
morphogenetic protein-4 was completely inhibited by ectopic expression of the
AVNR variant. The AVNR variant should prove to be a useful inhibitor in
identifying the specific role of furin.
PMID- 23155058
TI - 'Lung cancer and tobacco consumption': technical evaluation of the 1943 paper by
Schairer and Schoeniger published in Nazi Germany.
PMID- 23155059
TI - Totally drug-resistant tuberculosis (TDR-TB) in India: every dark cloud has a
silver lining.
PMID- 23155060
TI - On the usefulness of ontologies in epidemiology research and practice.
PMID- 23155061
TI - RNApathwaysDB--a database of RNA maturation and decay pathways.
AB - Many RNA molecules undergo complex maturation, involving e.g. excision from
primary transcripts, removal of introns, post-transcriptional modification and
polyadenylation. The level of mature, functional RNAs in the cell is controlled
not only by the synthesis and maturation but also by degradation, which proceeds
via many different routes. The systematization of data about RNA metabolic
pathways and enzymes taking part in RNA maturation and degradation is essential
for the full understanding of these processes. RNApathwaysDB, available online at
http://iimcb.genesilico.pl/rnapathwaysdb, is an online resource about maturation
and decay pathways involving RNA as the substrate. The current release presents
information about reactions and enzymes that take part in the maturation and
degradation of tRNA, rRNA and mRNA, and describes pathways in three model
organisms: Escherichia coli, Saccharomyces cerevisiae and Homo sapiens.
RNApathwaysDB can be queried with keywords, and sequences of protein enzymes
involved in RNA processing can be searched with BLAST. Options for data
presentation include pathway graphs and tables with enzymes and literature data.
Structures of macromolecular complexes involving RNA and proteins that act on it
are presented as 'potato models' using DrawBioPath-a new javascript tool.
PMID- 23155062
TI - Crenarchaeal chromatin proteins Cren7 and Sul7 compact DNA by inducing rigid
bends.
AB - Archaeal chromatin proteins share molecular and functional similarities with both
bacterial and eukaryotic chromatin proteins. These proteins play an important
role in functionally organizing the genomic DNA into a compact nucleoid. Cren7
and Sul7 are two crenarchaeal nucleoid-associated proteins, which are
structurally homologous, but not conserved at the sequence level. Co-crystal
structures have shown that these two proteins induce a sharp bend on binding to
DNA. In this study, we have investigated the architectural properties of these
proteins using atomic force microscopy, molecular dynamics simulations and
magnetic tweezers. We demonstrate that Cren7 and Sul7 both compact DNA molecules
to a similar extent. Using a theoretical model, we quantify the number of
individual proteins bound to the DNA as a function of protein concentration and
show that forces up to 3.5 pN do not affect this binding. Moreover, we
investigate the flexibility of the bending angle induced by Cren7 and Sul7 and
show that the protein-DNA complexes differ in flexibility from analogous
bacterial and eukaryotic DNA-bending proteins.
PMID- 23155063
TI - The UCSC Genome Browser database: extensions and updates 2013.
AB - The University of California Santa Cruz (UCSC) Genome Browser
(http://genome.ucsc.edu) offers online public access to a growing database of
genomic sequence and annotations for a wide variety of organisms. The Browser is
an integrated tool set for visualizing, comparing, analysing and sharing both
publicly available and user-generated genomic datasets. As of September 2012,
genomic sequence and a basic set of annotation 'tracks' are provided for 63
organisms, including 26 mammals, 13 non-mammal vertebrates, 3 invertebrate
deuterostomes, 13 insects, 6 worms, yeast and sea hare. In the past year 19 new
genome assemblies have been added, and we anticipate releasing another 28 in
early 2013. Further, a large number of annotation tracks have been either added,
updated by contributors or remapped to the latest human reference genome. Among
these are an updated UCSC Genes track for human and mouse assemblies. We have
also introduced several features to improve usability, including new navigation
menus. This article provides an update to the UCSC Genome Browser database, which
has been previously featured in the Database issue of this journal.
PMID- 23155064
TI - MetalPDB: a database of metal sites in biological macromolecular structures.
AB - We present here MetalPDB (freely accessible at http://metalweb.cerm.unifi.it), a
novel resource aimed at conveying the information available on the three
dimensional (3D) structures of metal-binding biological macromolecules in a
consistent and effective manner. This is achieved through the systematic and
automated representation of metal-binding sites in proteins and nucleic acids by
way of Minimal Functional Sites (MFSs). MFSs are 3D templates that describe the
local environment around the metal(s) independently of the larger context of the
macromolecular structure embedding the site(s), and are the central objects of
MetalPDB design. MFSs are grouped into equistructural (broadly defined as sites
found in corresponding positions in similar structures) and equivalent sites
(equistructural sites that contain the same metals), allowing users to easily
analyse similarities and variations in metal-macromolecule interactions, and to
link them to functional information. The web interface of MetalPDB allows access
to a comprehensive overview of metal-containing biological structures, providing
a basis to investigate the basic principles governing the properties of these
systems. MetalPDB is updated monthly in an automated manner.
PMID- 23155065
TI - A versatile cis-blocking and trans-activation strategy for ribozyme
characterization.
AB - Synthetic RNA control devices that use ribozymes as gene-regulatory components
have been applied to controlling cellular behaviors in response to environmental
signals. Quantitative measurement of the in vitro cleavage rate constants
associated with ribozyme-based devices is essential for advancing the molecular
design and optimization of this class of gene-regulatory devices. One of the key
challenges encountered in ribozyme characterization is the efficient generation
of full-length RNA from in vitro transcription reactions, where conditions
generally lead to significant ribozyme cleavage. Current methods for generating
full-length ribozyme-encoding RNA rely on a trans-blocking strategy, which
requires a laborious gel separation and extraction step. Here, we develop a
simple two-step gel-free process including cis-blocking and trans-activation
steps to support scalable generation of functional full-length ribozyme-encoding
RNA. We demonstrate our strategy on various types of natural ribozymes and
synthetic ribozyme devices, and the cleavage rate constants obtained for the RNA
generated from our strategy are comparable with those generated through
traditional methods. We further develop a rapid, label-free ribozyme cleavage
assay based on surface plasmon resonance, which allows continuous, real-time
monitoring of ribozyme cleavage. The surface plasmon resonance-based
characterization assay will complement the versatile cis-blocking and trans
activation strategy to broadly advance our ability to characterize and engineer
ribozyme-based devices.
PMID- 23155066
TI - DiffSplice: the genome-wide detection of differential splicing events with RNA
seq.
AB - The RNA transcriptome varies in response to cellular differentiation as well as
environmental factors, and can be characterized by the diversity and abundance of
transcript isoforms. Differential transcription analysis, the detection of
differences between the transcriptomes of different cells, may improve
understanding of cell differentiation and development and enable the
identification of biomarkers that classify disease types. The availability of
high-throughput short-read RNA sequencing technologies provides in-depth sampling
of the transcriptome, making it possible to accurately detect the differences
between transcriptomes. In this article, we present a new method for the
detection and visualization of differential transcription. Our approach does not
depend on transcript or gene annotations. It also circumvents the need for full
transcript inference and quantification, which is a challenging problem because
of short read lengths, as well as various sampling biases. Instead, our method
takes a divide-and-conquer approach to localize the difference between
transcriptomes in the form of alternative splicing modules (ASMs), where
transcript isoforms diverge. Our approach starts with the identification of ASMs
from the splice graph, constructed directly from the exons and introns predicted
from RNA-seq read alignments. The abundance of alternative splicing isoforms
residing in each ASM is estimated for each sample and is compared across sample
groups. A non-parametric statistical test is applied to each ASM to detect
significant differential transcription with a controlled false discovery rate.
The sensitivity and specificity of the method have been assessed using simulated
data sets and compared with other state-of-the-art approaches. Experimental
validation using qRT-PCR confirmed a selected set of genes that are
differentially expressed in a lung differentiation study and a breast cancer data
set, demonstrating the utility of the approach applied on experimental biological
data sets. The software of DiffSplice is available at
http://www.netlab.uky.edu/p/bioinfo/DiffSplice.
PMID- 23155067
TI - Purification of DNA-origami nanostructures by rate-zonal centrifugation.
AB - Most previously reported methods for purifying DNA-origami nanostructures rely on
agarose-gel electrophoresis (AGE) for separation. Although AGE is routinely used
to yield 0.1-1 ug purified DNA nanostructures, obtaining >100 ug of purified DNA
origami structure through AGE is typically laborious because of the post
electrophoresis extraction, desalting and concentration steps. Here, we present a
readily scalable purification approach utilizing rate-zonal centrifugation, which
provides comparable separation resolution as AGE. The DNA nanostructures remain
in aqueous solution throughout the purification process. Therefore, the desired
products are easily recovered with consistently high yield (40-80%) and without
contaminants such as residual agarose gel or DNA intercalating dyes. Seven
distinct three-dimensional DNA-origami constructs were purified at the scale of
0.1-100 ug (final yield) per centrifuge tube, showing the versatility of this
method. Given the commercially available equipment for gradient mixing and
fraction collection, this method should be amenable to automation and further
scale up for preparation of larger amounts (e.g. milligram quantities) of DNA
nanostructures.
PMID- 23155077
TI - Ocular disease in working horses in Ethiopia: a cross-sectional study.
AB - Ocular disease is a frequent finding in working horses. This study aimed to
estimate the prevalence and types of ocular pathology, and explore risk factors
potentially associated with disease within a population of working horses in
Ethiopia. In total, 1049 horses were selected from horses attending clinics run
by the Society for Protection of Animals Abroad (SPANA). Each had an ophthalmic
examination conducted under field conditions using a pen-torch. All owners
completed a short questionnaire. The prevalence of ocular abnormalities was 23.5
per cent (95 per cent confidence interval (CI) 18.0 per cent to 30.1 per cent)
and the percentage of horses with an abnormality in at least one eye was 43 per
cent (95 per cent CI 28.7 per cent to 58.4 per cent), although this varied
between towns. Mild eye pathology and end-stage disease with irreversible
pathology were most common. There were significantly more eye abnormalities in
the right eye compared with the left, and older horses were more likely to have
ocular pathology. Only 55.1 per cent of owners had noticed there was an ocular
abnormality present, and only 2.2 per cent had received any previous treatment
for eye disease. Only 1.9 per cent presented to the clinic because of an eye
problem. There appears to be either a lack of owner awareness, or a low
perception of the importance of eye disease among owners.
PMID- 23155078
TI - Serotonergic and cholinergic elements of the hypoxic ventilatory response in
developing zebrafish.
AB - The chemosensory roles of gill neuroepithelial cells (NECs) in mediating the
hyperventilatory response to hypoxia are not clearly defined in fish. While
serotonin (5-HT) is the predominant neurotransmitter in O(2)-sensitive gill NECs,
acetylcholine (ACh) plays a more prominent role in O(2) sensing in terrestrial
vertebrates. The present study characterized the developmental chronology of
potential serotonergic and cholinergic chemosensory pathways of the gill in the
model vertebrate, the zebrafish (Danio rerio). In immunolabelled whole gills from
larvae, serotonergic NECs were observed in epithelia of the gill filaments and
gill arches, while non-serotonergic NECs were found primarily in the gill arches.
Acclimation of developing zebrafish to hypoxia (P(O2)=75 mmHg) reduced the number
of serotonergic NECs observed at 7 days post-fertilization (d.p.f.), and this
effect was absent at 10 d.p.f. In vivo administration of 5-HT mimicked hypoxia by
increasing ventilation frequency (f(V)) in early stage (7-10 d.p.f.) and late
stage larvae (14-21 d.p.f.), while ACh increased f(V) only in late stage larvae.
In time course experiments, application of ketanserin inhibited the
hyperventilatory response to acute hypoxia (P(O2)=25 mmHg) at 10 d.p.f., while
hexamethonium did not have this effect until 12 d.p.f. Cells immunoreactive for
the vesicular acetylcholine transporter (VAChT) began to appear in the gill
filaments by 14 d.p.f. Characterization in adult gills revealed that VAChT
positive cells were a separate population of neurosecretory cells of the gill
filaments. These studies suggest that serotonergic and cholinergic pathways in
the zebrafish gill develop at different times and contribute to the
hyperventilatory response to hypoxia.
PMID- 23155079
TI - Mechanical and energetic scaling relationships of running gait through ontogeny
in the ostrich (Struthio camelus).
AB - It is unclear whether small animals, with their high stride frequency and
crouched posture, or large animals, with more tendinous limbs, are more reliant
on storage and return of elastic energy during locomotion. The ostrich has a limb
structure that appears to be adapted for high-speed running with long tendons and
short muscle fibres. Here we investigate biomechanics of ostrich gait through
growth and, with consideration of anatomical data, identify scaling relationships
with increasing body size, relating to forces acting on the musculoskeletal
structures, effective mechanical advantage (EMA) and mechanical work. Kinematic
and kinetic data were collected through growth from running ostriches. Joint
moments scaled in a similar way to the pelvic limb segments as a result of
consistent posture through growth, such that EMA was independent of body mass.
Because no postural change was observed, relative loads applied to
musculoskeletal tissues would be predicted to increase during growth, with
greater muscle, and hence tendon, load allowing increased potential for elastic
energy storage with increasing size. Mass-specific mechanical work per unit
distance was independent of body mass, resulting in a small but significant
increase in the contribution of elastic energy storage to locomotor economy in
larger ostriches.
PMID- 23155080
TI - Shelter availability, stress level and digestive performance in the aspic viper.
AB - The lack of shelter can perturb behaviors, increase stress level and thus alter
physiological performance (e.g. digestive, immune or reproductive functions).
Although intuitive, such potential impacts of lack of shelter remain poorly
documented. We manipulated shelter availability and environmental and
physiological variables (i.e. access to a heat source, predator attack, feeding
status) in a viviparous snake, and assessed sun-basking behavior, digestive
performance (i.e. digestive transit time, crude estimate of assimilation,
regurgitation rate) and plasma corticosterone levels (a proxy of stress level).
Shelter deprivation provoked a strong increase in sun-basking behavior and thus
elevated body temperature, even in unfed individuals for which energy savings
would have been otherwise beneficial. The lack of heat was detrimental to
digestive performance; simulated predator attacks worsened the situation and
entailed a further deterioration of digestion. The combination of the lack of
shelter with cool ambient temperatures markedly elevated basal corticosterone
level and was associated with low digestive performance. This hormonal effect was
absent when only one negative factor was involved, suggesting a threshold
response. Overall, our results revealed important non-linear cascading impacts of
shelter availability on stress-hormone levels, behaviors and physiological
performance. These results infer that shelter availability is important for
laboratory studies, captive husbandry and possibly conservation plans.
PMID- 23155081
TI - Iodine accumulation in sea urchin larvae is dependent on peroxide.
AB - Iodine has many important biological functions and its concentrations vary with
the environment. Recent research has provided novel insights into iodine uptake
mechanisms in marine bacteria and kelp through hydrogen peroxide-dependent
diffusion (PDD). This mechanism is distinct from sodium-dependent mechanisms
known from vertebrates. In vertebrates, iodine accumulates in the thyroid gland
by the action of the apical iodide transporter (AIT) and the sodium/iodide
symporter (NIS). Neither of these proteins has, thus far, been identified outside
of the chordates, and PDD (as an iodine uptake mechanism) has never been studied
in animals. Using (125)I as a marker for total iodine influx, we tested iodine
uptake via sodium-dependent transport versus PDD in embryos and larvae of the sea
urchin Strongylocentrotus purpuratus. We found that iodine uptake in S.
purpuratus is largely independent of NIS/AIT. Instead, we found that uptake is
dependent on the presence and production of hydrogen peroxide, indicating that
sea urchin larvae use PDD as a mechanism for iodine acquisition. Our data, for
the first time, provide conclusive evidence for this mechanism in an animal.
Furthermore, our data provide preliminary evidence that sodium-dependent iodine
uptake via active transporter proteins is a synapomorphy of vertebrates.
PMID- 23155083
TI - Temperature-dependent behaviours are genetically variable in the nematode
Caenorhabditis briggsae.
AB - Temperature-dependent behaviours in Caenorhabditis elegans, such as thermotaxis
and isothermal tracking, are complex behavioural responses that integrate
sensation, foraging and learning, and have driven investigations to discover many
essential genetic and neural pathways. The ease of manipulation of the
Caenorhabditis model system also has encouraged its application to comparative
analyses of phenotypic evolution, particularly contrasts of the classic model C.
elegans with C. briggsae. And yet few studies have investigated natural genetic
variation in behaviour in any nematode. Here we measure thermotaxis and
isothermal tracking behaviour in genetically distinct strains of C. briggsae,
further motivated by the latitudinal differentiation in C. briggsae that is
associated with temperature-dependent fitness differences in this species. We
demonstrate that C. briggsae performs thermotaxis and isothermal tracking largely
similar to that of C. elegans, with a tendency to prefer its rearing temperature.
Comparisons of these behaviours among strains reveal substantial heritable
natural variation within each species that corresponds to three general patterns
of behavioural response. However, intraspecific genetic differences in thermal
behaviour often exceed interspecific differences. These patterns of temperature
dependent behaviour motivate further development of C. briggsae as a model system
for dissecting the genetic underpinnings of complex behavioural traits.
PMID- 23155082
TI - Dietary composition regulates Drosophila mobility and cardiac physiology.
AB - The impact of dietary composition on exercise capacity is a subject of intense
study in both humans and model organisms. Interactions between diet and genetics
are a crucial component of optimized dietary design. However, the genetic factors
governing exercise response are still not well understood. The recent development
of invertebrate models for endurance exercise is likely to facilitate study
designs examining the conserved interactions between diet, exercise and genetics.
As a first step, we used the Drosophila model to describe the effects of varying
dietary composition on several physiological indices, including fatigue tolerance
and climbing speed, cardiac performance, lipid storage and autophagy. We found
that flies of two divergent genetic backgrounds optimize endurance and cardiac
performance on relatively balanced low calorie diets. When flies are provided
with unbalanced diets, diets higher in sugar than in yeast facilitate greater
endurance at the expense of cardiac performance. Importantly, we found that
dietary composition has a profound effect on various physiological indices,
whereas total caloric intake per se has very little predictive value for
performance. We also found that the effects of diet on endurance are completely
reversible within 48 h if flies are switched to a different diet.
PMID- 23155084
TI - Jumping mechanisms of treehopper insects (Hemiptera, Auchenorrhyncha,
Membracidae).
AB - The kinematics and jumping performance of treehoppers (Hemiptera,
Auchenorrhyncha, Membracidae) were analysed from high speed images. The eight
species analysed had an 11-fold range of body mass (3.8-41 mg) and a 2-fold range
of body length (4.1-8.4 mm). Body shape was dominated by a prothoracic helmet
that projected dorsally and posteriorly over the body, and in some species
forwards to form a protruding horn. Jumping was propelled by rapid depression of
the trochantera of the hindlegs. The hindlegs were only 30-60% longer than the
front and middle legs, and 47-94% the length of the body in different species.
They were slung beneath the body and moved together in the same plane. In
preparation for a jump, the hindlegs were initially levated and rotated forwards
so that the femora were pressed into indentations of the coxae. The tibiae were
flexed about the femora and the tarsi were placed on the ground directly beneath
the lateral edges of the abdomen. Movements of the front and middle legs adjusted
the angle of the body relative to the ground, but for most treehoppers this angle
was small, so that the body was almost parallel to the ground. The rapid
depression of the hindlegs accelerated the body to take-off in 1.2 ms in the
lighter treehoppers and 3.7 ms in the heavier ones. Take-off velocities of 2.1
2.7 m s(-1) were achieved and were not correlated with body mass. In the best
jumps, these performances involved accelerations of 560-2450 m s(-2) (g forces of
47-250), an energy expenditure of 13.5-101 MUJ, a power output of 12-32 mW and
exerted a force of 9.5-29 mN. The power output per mass of muscle far exceeds the
maximum active contractile limit of normal muscle. Such requirements indicate
that treehoppers must be using a power amplification mechanism in a catapult-like
action. Some jumps were preceded by flapping movements of the wings, but the
propulsive movements of the hindlegs were crucial in achieving take-off.
PMID- 23155085
TI - Multivariate analysis of behavioural response experiments in humpback whales
(Megaptera novaeangliae).
AB - The behavioural response study (BRS) is an experimental design used by field
biologists to determine the function and/or behavioural effects of conspecific,
heterospecific or anthropogenic stimuli. When carrying out these studies in
marine mammals it is difficult to make basic observations and achieve sufficient
samples sizes because of the high cost and logistical difficulties. Rarely are
other factors such as social context or the physical environment considered in
the analysis because of these difficulties. This paper presents results of a BRS
carried out in humpback whales to test the response of groups to one recording of
conspecific social sounds and an artificially generated tone stimulus.
Experiments were carried out in September/October 2004 and 2008 during the
humpback whale southward migration along the east coast of Australia. In total,
13 'tone' experiments, 15 'social sound' experiments (using one recording of
social sounds) and three silent controls were carried out over two field seasons.
The results (using a mixed model statistical analysis) suggested that humpback
whales responded differently to the two stimuli, measured by changes in course
travelled and dive behaviour. Although the response to 'tones' was consistent, in
that groups moved offshore and surfaced more often (suggesting an aversion to the
stimulus), the response to 'social sounds' was highly variable and dependent upon
the composition of the social group. The change in course and dive behaviour in
response to 'tones' was found to be related to proximity to the source, the
received signal level and signal-to-noise ratio (SNR). This study demonstrates
that the behavioural responses of marine mammals to acoustic stimuli are complex.
In order to tease out such multifaceted interactions, the number of replicates
and factors measured must be sufficient for multivariate analysis.
PMID- 23155086
TI - Cellular damage as induced by high temperature is dependent on rate of
temperature change - investigating consequences of ramping rates on molecular and
organismal phenotypes in Drosophila melanogaster.
AB - Ecological relevance and repeatability of results obtained in different
laboratories are key issues when assessing thermal tolerance of ectotherms.
Traditionally, assays have used acute exposures to extreme temperatures. The
outcomes of ecologically more relevant ramping experiments, however, are
dependent on the rate of temperature change leading to uncertainty of the causal
factor for loss of function. Here, we test the physiological consequences of
exposing female Drosophila melanogaster to gradually increasing temperatures in
so-called ramping assays. We exposed flies to ramping at rates of 0.06 and 0.1
degrees C min(-1), respectively. Flies were sampled from the two treatments at
28, 30, 32, 34, 36 and 38 degrees C and tested for heat tolerance and expression
levels of the heat shock genes hsp23 and hsp70, as well as Hsp70 protein. Heat
shock genes were upregulated more with a slow compared with a faster ramping
rate, and heat knock-down tolerance was higher in flies exposed to the faster
rate. The fact that slow ramping induces a stronger stress response (Hsp
expression) compared with faster ramping suggests that slow ramping induces more
heat damage at the cellular level due to longer exposure time. This is supported
by the observation that fast ramped flies have higher heat knock-down tolerance.
Thus we observed both accumulation of thermal damage at the molecular level and
heat hardening at the phenotypic level as a consequence of heat exposure. The
balance between these processes is dependent on ramping rate leading to the
observed variation in thermal tolerance when using different rates.
PMID- 23155087
TI - Sperm metabolism in pigs: a role for peroxisome proliferator-activated receptor
gamma (PPARgamma).
AB - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear hormone
receptor expressed predominantly in adipose tissue, also implicated in energy
homeostasis. In this study, we used western blotting and immunofluorescence
techniques to demonstrate for the first time that pig spermatozoa express
PPARgamma. To investigate the functional role of PPARgamma in pig sperm, we
evaluated its action on different events that characterize the biology of sperm
cells, i.e. motility, capacitation, viability and acrosome reaction, using the
PPARgamma-agonist 15-deoxy-12,14-prostaglandin J2 (PGJ2). In responses to PGJ2
treatment, motility, cholesterol efflux and tyrosine phosphorylation were
increased, which broadens the role of PPARgamma from that previously described in
the literature, as it also acts to improve sperm functionality. To further our
understanding of the significance of PPARgamma in pig sperm, we focused its
effects on lipid and glucose metabolism. Evaluation of triglyceride content and
lipase, acyl-CoA dehydrogenase and G6PDH activities suggests that PPARgamma
induces energy expenditure in pig spermatozoa. These data represent a meaningful
advance in the field of sperm energy metabolism. Taken together, our results
demonstrate for the first time that PPARgamma is expressed by pig sperm, thus
improving its functionalities in terms of motility, capacitation, acrosome
reaction, survival and metabolism.
PMID- 23155089
TI - Enhanced erythropoiesis in mice exposed to low environmental temperature.
AB - Hematopoietic responses to environmental factors are not fully characterized.
Polycythemia has been reported during exposure to low temperatures in ectothermic
animals. The relationship between the causes of polycythemia and erythropoiesis
during low temperature exposure is not fully understood. In this study, we
exposed C57BL/6 mice to 5 degrees C and monitored the blood cell counts and
erythropoiesis. The hematocrit level increased from 45.6 to 52.2% after 14 days.
Likewise, the hemoglobin concentration, initially 15.1 g dl(-1), rose to 16.0 g
dl(-1). The reticulocyte production index significantly increased from 4 to 8%
after 7 days. We examined the anatomy and cell composition of the spleens of the
mice. On day 5, the spleens were ~6 mg g(-1) of body mass, which was twofold
greater than the spleens on day 0. Flow cytometry showed fourfold more
proerythroblasts on day 5, compared with day 0. Additionally, the number of late
stage mature erythroblasts increased on day 14. Erythropoietin mRNA levels
increased in the kidneys, and hypoxia-inducible genes were enhanced in the
kidney. Our findings indicated that low ambient temperature is a novel
erythropoietic stress, which induces polycythemia by enhanced erythropoiesis.
PMID- 23155088
TI - Lion (Panthera leo) and caracal (Caracal caracal) type IIx single muscle fibre
force and power exceed that of trained humans.
AB - This study investigated for the first time maximum force production, shortening
velocity (Vmax) and power output in permeabilised single muscle fibres at 12
degrees C from lion, Panthera leo (Linnaeus 1758), and caracal, Caracal caracal
(Schreber 1776), and compared the values with those from human cyclists.
Additionally, the use and validation of previously frozen tissue for contractile
experiments is reported. Only type IIx muscle fibres were identified in the
caracal sample, whereas type IIx and only two type I fibres were found in the
lion sample. Only pure type I and IIa, and hybrid type IIax fibres were
identified in the human samples - there were no pure type IIx fibres.
Nevertheless, compared with all the human fibre types, the lion and caracal
fibres were smaller (P<0.01) in cross-sectional area (human: 6194+/-230 MUm(2),
lion: 3008+/-151 MUm(2), caracal: 2583+/-221 MUm(2)). On average, the felid type
IIx fibres produced significantly greater force (191-211 kN m(-2)) and ~3 times
more power (29.0-30.3 kN m(-2) fibre lengths s(-1)) than the human IIax fibres
(100-150 kN m(-2), 4-11 kN m(-2) fibre lengths s(-1)). Vmax values of the lion
type IIx fibres were also higher than those of human type IIax fibres. The
findings suggest that the same fibre type may differ substantially between
species and potential explanations are discussed.
PMID- 23155090
TI - Effect of fluid viscosity on the liquid-feeding flow phenomena of a female
mosquito.
AB - Liquid-sucking phenomena by the two-pump system of female mosquitoes were
investigated to understand the feeding mechanism. In most previous experimental
studies on liquid-feeding insects, the net increase of mass was divided by the
feeding time and fluid density to evaluate the intake rate. However, this
weighting method is not so precise for mosquitoes, because they are too
lightweight to measure the gain of mass accurately. In this study, the intake
rate of female mosquitoes feeding on various sucrose solutions was estimated
using a micro-particle image velocimetry technique. As the sucrose concentration
increased from 1% to 50%, the intake rate decreased from 17.3 to 5.8 nl s(-1). In
addition, the temporal volume variations of the two pump chambers were estimated
based on the velocity and acceleration information of the flow at the center of
the food canal of the proboscis. One pumping period was divided into four
elementary phases, which are related to the different operational modes of the
two pumps. According to the hypothetical model established in this study, the
phase shift () between the two pump chambers increases from 14 to 28 ms and the
percentage of reverse flow to forward flow in a pumping period decreases from
7.6% to 1.7% with increasing viscosity. The developed analytical methodology thus
aids in the study of an insect's feeding mechanism.
PMID- 23155091
TI - Integration of alternating monocular samples during goal-directed aiming.
AB - The current study examined the effect of interocular delay in a manual aiming
task that required accurate end-point placement, but not precise control of a
grip aperture. Participants aimed in binocular, monocular, or alternating
monocular vision conditions. For the latter, 25ms monocular samples were provided
to alternate eyes without delay (0ms), or a delay of 25 or 50ms. The interocular
delay resulted in a longer movement time, caused by a longer time-to-peak and
time-after-peak velocity, and a reduction in peak velocity. We suggest that the
change in kinematics reflect a strategic response to preserve terminal aiming
accuracy and variability when faced with an informational perturbation. These
findings indicate that the response to the interocular delay between alternating
monocular samples depends on the task-specific information used to control that
behavior.
PMID- 23155092
TI - Anchoring in rhythmic in-phase and antiphase visuomotor tracking.
AB - Rhythmic limb movements are often anchored at particular points in the movement
cycle. Anchoring may reveal essential task-specific information for motor
control. We examined the effect of tracking mode (in-phase, antiphase) and gaze
direction (left, right) on anchoring in visuomotor tracking with and without
concurrent visual feedback of the hand movement. For in-phase tracking, anchoring
was observed at the foveated reversal point whereas for antiphase tracking
anchoring was observed at both reversals, suggesting the presence of two
reference points instead of one. Anchoring at the foveated reversal reflected
gaze anchoring (i.e., coalignment of hand and gaze) while anchoring at the
nonfoveated reversal reflected visuomotor synchronization (i.e., the hand was
steered to the nonfoveated reversal coincident with a target reversal at the
point of gaze). We propose that the number and location of anchor points play a
crucial role in the underlying control by providing reference values for error
correction processes.
PMID- 23155094
TI - Hepatitis B seroprevalence in persons attending youth clinics in Stockholm,
Sweden in 2008.
AB - Sweden is a low endemicity country for hepatitis B virus (HBV). The previously
reported prevalence of chronic HBV is <1% and of overall markers <5%. HBV is not
included in the universal childhood vaccination programme. Instead, selected high
risk groups are targeted. Our aim was to examine the HBV seroprevalence in youth
clinic clients in Stockholm and identify if this population might be a new target
group for vaccination. In total, 515 clients aged 18-22 years were recruited.
They completed a risk-assessment questionnaire and 464 (90%) had a serum specimen
tested for HBV serology. Chronic HBV was found in 0.6% and 0.9% had previously
been infected with HBV. A seroprevalence of 1.8% HBV markers was found among non
vaccinated persons. This is lower than reported from other countries and not
different from the general population in Sweden. However, in persons originating
from HBV endemic countries (n = 123), the prevalence was higher, 6.5%. Only 14%
were vaccinated and the majority hence susceptible to HBV. The target groups are
not reached by the present vaccination strategy. Youth clinics are ideal settings
for catch-up vaccination.
PMID- 23155093
TI - Herpes simplex virus type 2 infection as a biomarker for sexual debut among young
people in sub-Saharan Africa: a literature review.
AB - Biological markers are needed in order to provide objective measures to validate
self-reported sexual behaviour and interpret prevention trial data. In this
review, we evaluated herpes simplex type 2 virus (HSV-2), one of the most
prevalent sexually transmitted infections in sub-Saharan Africa as a biological
marker of sexual debut. Based on our findings, we do not recommend using HSV-2 as
a biomarker for sexual debut due to its low transmission probabilities and the
fact that HSV-2 prevalence is not 100% among potential sexual partners. We
recommend that the validation of alternative biological measures should be
prioritized, and included in future studies and trials of interventions to reduce
sexual health risk.
PMID- 23155095
TI - Education provided to outgoing UK medical elective students regarding HIV risk
and post exposure prophylaxis.
AB - Previous studies suggested medical schools were failing to provide sufficient
support for students undertaking electives in areas with high HIV prevalence and
despite updated Department of Health (DoH) guidelines, not all were advising post
exposure prophylaxis (PEP) starter packs where appropriate. This study assessed
whether there has been improvement in risk reduction provided by home
institutions. Questionnaires were emailed to all 29 UK medical schools offering
an elective. A total of 26 medical schools responded. Only one failed to offer
PEP starter packs or advice on where to obtain one. Support and advice provided
by the other 25 varied considerably. HIV risk education and provision of PEP to
elective students has improved. A discrepancy between advice given, supervision
of projects and provision of PEP starter packs across UK medical schools remains.
We reiterate recommendations put forward previously that there is a need for
regularly updated national guidelines published by experts, issued to all medical
schools.
PMID- 23155097
TI - Chlamydia trachomatis, Mycoplasma genitalium and Ureaplasma urealyticum in
clinical and non-clinical settings, Arkhangelsk Oblast, Russia.
AB - Russia and Eastern Europe have the fastest growing HIV epidemic in the world. As
sexually transmitted infections (STIs) play an important role in HIV
transmission, we conducted this study to find the prevalence of three
microorganisms associated with STIs in Arkhangelsk Oblast, Russia. First void
urine from 1729 participants was analysed using nucleic acid amplification
testing, and all participants completed a questionnaire. One hundred and twelve
(6.5%) were tested positive for Chlamydia trachomatis, 67 (3.9%) for Mycoplasma
genitalium and 221 (12.8%) for Ureaplasma urealyticum. A significant association
was found between C. trachomatis and U. urealyticum (odds ratio [OR] 1.85; 95%
confidence interval [CI] 1.1 to 3.0). U. urealyticum was associated with similar
social demographics and sexual risks as C. trachomatis and M. genitalium. This
suggests that U. urealyticum has a possible role as an STI pathogen or might be a
contributing factor for the spread of other STIs.
PMID- 23155096
TI - Stimulating an immune response? Oral sex is associated with less endometritis.
AB - Secondary analysis of the PID Evaluation and Clinical Health (PEACH) data
suggests that among women presenting with signs and symptoms of pelvic
inflammatory disease (PID), those who reported oral sex were less likely to have
endometritis (adjusted odds ratio [OR] 0.5 [0.3-0.8]) than those who did not
report oral sex. Adaptive immunity requires antigenic priming of the lymphatic
system. As lymphatic tissue is abundant in the oropharynx, oral sex could lead to
effective immune stimulation and prevent PID. To determine whether oral sex could
be a protective factor for PID the relationship between self-reported oral sex
and endometritis was analysed among 619 women with clinically suspected PID who
participated in the PEACH study. Nearly one quarter of participants reported oral
sex in the past four weeks. These women also reported a higher number of sexual
partners, a new partner within the past four weeks and a higher frequency of
sexual intercourse (all P < 0.03). They were more likely to smoke (P < 0.0001),
drink alcohol (P < 0.004) and use recreational drugs (P < 0.02). Participants
reporting oral sex were significantly less likely to be black or to have a
positive test for Neisseria gonorrhoeae (7.8% versus 21.6%, P = 0.001). Women who
disclosed oral sex were significantly less likely to have endometritis after
adjusting for race, number of partners, recent new partner, smoking, alcohol use
and drug use (adjusted OR 0.5 [0.3-0.8]). This is the first paper showing a
negative association between oral sex and endometritis. This may be mediated by a
protective immune response in the genital tract following priming in the
oropharynx. This hypothesis needs to be tested in further studies.
PMID- 23155098
TI - Rising popularity of anal intercourse and sexual risk taking: findings from two
national probability studies of young Croatian adults.
AB - This study examined the prevalence and correlates of heterosexual anal
intercourse in two national probability samples of young Croatian adults aged 18
25 years, which were collected in 2005 and 2010. The lifetime prevalence of anal
intercourse increased from 27% to 36%. In multivariate analysis, reporting four
or more lifetime sexual partners was the only correlate of the experience of anal
intercourse that was significant among both women (odds ratios [ORs] = 1.78-3.27,
P < 0.05) and men (ORs = 3.14-4.63, P < 0.01). Information about condom use at
most recent anal intercourse was collected in the 2010 study wave only. Age (OR =
0.80, P < 0.05), female gender (OR = 0.29, P < 0.01), holding more negative
attitudes towards condoms (OR = 0.28-0.32, P < 0.05) and reporting condom use at
most recent vaginal intercourse (OR = 11.45, 95% Confidence interval [CI] = 5.68
23.06) were associated with using a condom at most recent anal intercourse. Given
the substantial prevalence of anal intercourse among young heterosexual adults
and considerable sexually transmitted infection/HIV risks associated with the
practice, sex education programmes should promote the discussion of health risks
associated with anal eroticism.
PMID- 23155099
TI - Association between smoking and size of anal warts in HIV-infected women.
AB - While the association between smoking and human papillomavirus infection,
cervical cancer, and anal cancer has been well studied, evidence on the
association between cigarette smoking and anal warts is limited. The purpose of
this study was to investigate if cigarette smoking status influences the size of
anal warts over time in HIV-infected women in a sample of 976 HIV-infected women
from the Women's Interagency HIV Study (WIHS). A linear mixed model was used to
determine the effect of smoking on anal wart size. Even though women who were
currently smokers had larger anal warts at baseline and slower growth rate of
anal wart size after each visit than women who were not current smokers, there
was no association between size of anal wart and current smoking status over
time. Further studies on the role of smoking and interaction between smoking and
other risk factors, however, should be explored.
PMID- 23155101
TI - Managing HIV in pregnancy in a community-based sexual health clinic: a decade in
review.
AB - The management of HIV in pregnancy has evolved significantly over the past 10
years as our experience of combination antiretroviral therapy (ART) has grown. We
reviewed 109 pregnancies which were managed at our community-based integrated HIV
and sexual health clinic to investigate preconception and antenatal care, and
trends in ART over time. We document an increasing proportion of pregnancies in
which the mother was aware of her HIV status pre-conception and conception on
ART. Pre-conception care was sought in a minority of cases, and many women did
not present for first antenatal review until the end of the second trimester. Of
108 live births, there was one case of vertical transmission (0.93%). While our
study demonstrates the efficacy of current strategies to prevent mother to child
transmission of HIV infection, more could be done to encourage HIV-positive women
to seek preconception advice and to attend for early review in the first
trimester.
PMID- 23155100
TI - Evaluating the implementation of nurse-initiated HIV rapid testing in three
Veterans Health Administration substance use disorder clinics.
AB - Individuals with substance use disorders (SUDs) are at higher risk of HIV
infection, yet recent studies show rates of HIV testing are low among this
population. We implemented and evaluated a nurse-initiated HIV oral rapid testing
(NRT) strategy at three Veterans Health Administration SUD clinics.
Implementation of NRT includes streamlined nurse training and a computerized
clinical reminder. The evaluation employed qualitative interviews with staff and
a quantitative evaluation of HIV testing rates. Barriers to testing included lack
of laboratory support and SUD nursing resistance to performing medical
procedures. Facilitators included the ease of NRT integration into workflow,
engaged management and an existing culture of disease prevention. Six-months post
intervention, rapid testing rates at SUD clinics in sites 1, 2, and 3 were 5.0%,
1.1% and 24.0%, respectively. Findings indicate that NRT can be successfully
incorporated into some types of SUD subclinics with minimal perceived impact on
workflow and time.
PMID- 23155102
TI - Association between herpes simplex virus type 2 and HIV-1 in a population of
married couples from Dakar, Senegal.
AB - Numerous studies suggest that herpes simplex virus type 2 (HSV-2) increases the
risk of HIV-1 infection but recent clinical trials of HSV-2 suppressive therapy
failed to show an effect. We assessed the putative association between HSV-2 and
HIV-1 in a population of HIV-concordant-negative, HIV-1-discordant and HIV-1
concordant-positive married couples from Dakar, Senegal. In agreement with
previous studies, we observed a strong overall association between HSV-2 and HIV
1 (odds ratio 4.61; P < 0.001). However, this association was mainly determined
by a low HSV-2 prevalence in HIV-concordant-negative couples compared with HIV-1
discordant and HIV-1-concordant-positive couples (23% versus 59% and 66%,
respectively; P < 0.001). We observed no further differences in HSV-2 prevalence
between HIV-1-discordant and HIV-1-concordant-positive couples (59% and 66%,
respectively; P = 0.483). Neither the index (59% versus 62%, P = 1.000) nor
recipient partners (41% versus 63%, P = 0.131) in HIV-1-discordant and HIV-1
concordant-positive couples showed significant differences in HSV-2 prevalence.
HSV-2 does not constitute a clear risk factor for HIV-1 infection in this
population.
PMID- 23155103
TI - HIV testing and counselling in Colombia: evidence from a national health survey
and recommendations for health-care services.
AB - The purpose of this study was to assess the prevalence of, and the factors
associated with HIV testing and pre- and post-test counselling (PPTC) in
Colombia. Cross-sectional data from the National Health Survey carried out during
2007 were analysed. Data were gathered from records of 29,760 individuals between
the ages of 18 and 69 from the main regions of the country. Only 19.7% of the
sample had taken an HIV test. Men, people with no education, those not affiliated
with the health-care system, residents of rural areas and those aged older than
65 were less likely to have been tested for HIV; 42% of those tested did not
receive pre-test counselling and 56.9% received no report of the results.
Considering the low prevalence of HIV testing among the Colombian population, it
is necessary to design and apply guidelines for HIV screening in all health-care
settings and to conduct targeted testing in high-risk sub-populations. A national
norm of PPTC in those who undergo HIV testing should be examined.
PMID- 23155104
TI - Most adolescents who participate in school-based screenings for sexually
transmitted infections do not perceive themselves at high risk of sexually
transmitted infection.
AB - Statements of study limitations have been made in a number of reports that
voluntary participants in school-based screenings for sexually transmitted
infections (STIs) may be individuals who self-select for participation because
they perceive themselves at high risk of STI. We surveyed 3336 students
participating in the New Orleans school-based screening for chlamydia and
gonorrhoea to determine their perceived personal risk of STI. Among all screening
participants, 1183 (35.5%) estimated that their chances of getting an STI were
pretty high or very high and 2153 (64.5%) estimated that their chances were none,
not very high or medium. These findings indicate that most participants in the
New Orleans school-based screening for chlamydia and gonorrhoea do not perceive
themselves at high risk of STI.
PMID- 23155105
TI - An audit of partner notification for syphilis and HIV.
AB - Partner notification (PN) is a vital tool used by genitourinary (GU) medicine
services in the public health control of sexually transmitted infections. We
audited our PN outcomes for syphilis and HIV, over an 18-month period, at the
Edinburgh GUM clinic. Follow-up information on testing was only available for 58%
of traceable syphilis contacts and 59% of traceable HIV contacts, though
substantially larger percentages in each case, respectively 78% and 90%, were
informed regarding their risk of exposure. Furthermore, the department achieved
screening verification in 78% of identifiable syphilis contacts and 94% of
identifiable HIV partners.
PMID- 23155106
TI - Unmasking of progressive multifocal leukoencephalopathy in a patient with HIV-2.
AB - HIV-2 is common in West Africa but rarely found in developed countries. It
usually has a milder disease course than HIV-1 and clinical presentations of
neurological syndromes in HIV-2 are extremely rare. We report a case of a HIV-2
infected, 46-year-old woman originally from Cote d'Ivoire who presented with
possible intracerebral toxoplasmosis infection then developed progressive
multifocal leukoencephalopathy.
PMID- 23155107
TI - Idiopathic ileocolitis with perforation associated with HIV infection:
thalidomide treatment.
AB - Idiopathic cutaneous ulcers, oesophageal ulcers and severe ulcerative ileocolitis
occurred in a human immunodeficiency virus (HIV)-infected patient early after the
initiation of combination antiretroviral therapy. This massive inflammatory
process led to acute colonic perforation on two occasions. The disease was
refractory to standard therapy, but responded successfully to thalidomide. Here,
we discuss the potential benefits of thalidomide in refractory inflammatory
processes in HIV-infected patients.
PMID- 23155108
TI - Visiting friends and relatives may be a risk for non-adherence for HIV-positive
travellers.
AB - We report three cases of immigrants to Australia, living with HIV/AIDS, who,
while travelling in countries of origin or migration, were unable to continue to
take their antiretrovirals appropriately. We discuss the possible reasons for
this and ways to reduce the possibility of it happening. Travel may be a
significant risk factor for non-adherence; pre-travel advice and planning might
help to prevent it occurring.
PMID- 23155109
TI - Genital elephantiasis due to donovanosis: forgotten but not gone yet ...
AB - Genital elephantiasis is a disease that is characterized by massive enlargement
of the genitalia. Early aetiological diagnosis is of paramount importance so that
development of genital elephantiasis can be prevented; otherwise it is not
completely reversible with medical therapy and often requires surgical
intervention. Chronic mental distress and disability can result as it interferes
with daily/routine activities of the affected individual. Over time, the
infectious causes of genital elephantiasis have evolved, from syphilis in the pre
penicillin era to donovanosis, lymphogranuloma venereum and recently filariasis,
tuberculosis, leishmaniasis, HIV and chromoblastomycosis. With a declining
prevalence globally, donovanosis is at risk of being forgotten as a cause of
genital swelling; however, it is known to persist for years without treatment and
can lead to complications such as lymphoedema and genital mutilation. We herein
present a case of genital elephantiasis that was eventually diagnosed as being
due to donovanosis.
PMID- 23155110
TI - Resection of PCNSL, if safely possible, seems to be better than biopsy:
challenging a paradigm?
PMID- 23155112
TI - Ultrathin specimen preparation by a low-energy Ar-ion milling method.
AB - The low-energy Ar-ion milling method was used to prepare ultrathin specimens for
transmission electron microscope observation. The samples were thinned initially
by a usual focused ion beam technique or typical Ar-ion milling with a high
energy of 2-10 keV and were thinned additionally by an Ar-ion beam with an energy
less than 1 keV, typically 500-900 eV. This low-energy ion beam was scanned over
the specimen, and secondary electrons induced by the ion beam could be detected
to form secondary electron images with a resolution of a few micrometre. Because
a desired area can be selected and thinned by the low-energy ion beam,
redeposition or cross contamination from irradiation of a metal grid that
supports the sample can be prevented. It was shown that the low-energy Ar-ion
beam thins a surface amorphous damage layer preferentially and effectively rather
than a crystal specimen. Images from ultrathin specimens of two different
materials revealed a detailed structure.
PMID- 23155113
TI - A new F-actin structure in fungi: actin ring formation around the cell nucleus of
Cryptococcus neoformans.
AB - The F-actin cytoskeleton of Cryptococcus neoformans is known to comprise actin
cables, cortical patches and cytokinetic ring. Here, we describe a new F-actin
structure in fungi, a perinuclear F-actin collar ring around the cell nucleus, by
fluorescent microscopic imaging of rhodamine phalloidin-stained F-actin.
Perinuclear F-actin rings form in Cryptococcus neoformans treated with the
microtubule inhibitor Nocodazole or with the drug solvent dimethyl sulfoxide
(DMSO) or grown in yeast extract peptone dextrose (YEPD) medium, but they are
absent in cells treated with Latrunculin A. Perinuclear F-actin rings may
function as 'funicular cabin' for the cell nucleus, and actin cables as
intracellular 'funicular' suspending nucleus in the central position in the cell
and moving nucleus along the polarity axis along actin cables.
PMID- 23155114
TI - A pilot study of the effectiveness of home teleconsultations in paediatric
palliative care.
AB - We conducted a pilot study to investigate the effectiveness of a home telehealth
service for paediatric palliative care consultations. Over a 10 week period, 14
of the 17 caregivers approached to be part of the study agreed to participate.
Families were allocated, non-randomly, to a control group (usual care) or an
intervention group (usual care with the addition of home telehealth
consultations). The primary outcome measure was quality-of-life score. Caregivers
were surveyed for up to 99 days following recruitment. A descriptive analysis of
the quality-of-life data showed no differences between caregivers in the two
groups. However, important lessons were learnt regarding factors which influence
the success of studies in this population group, and the domains of caregiver
quality-of-life that warrant intervention. Palliative care is complex, and
multiple interventions and supports are required if care is to be managed at
home. Home telehealth consultations are a feasible and acceptable means of
facilitating a palliative care consultation which can reduce the burden on
families at a distressing time.
PMID- 23155115
TI - Tremor irregularity, torque steadiness and rate of force development in
Parkinson's disease.
AB - We investigated lower-extremity isometric tremor Approximate Entropy
(irregularity), torque steadiness and rate of force development (RFD) and their
associations to muscle activation strategy during isometric knee extensions in
patients with Parkinson's disease (PD). Thirteen male patients with idiopathic PD
and 15 neurologically healthy matched controls performed isometric maximal
contractions (extension/flexion) as well as steady submaximal and powerful
isometric knee extensions. The patients with PD showed decreased isometric tremor
irregularity. Torque steadiness was reduced in PD and the patients had increased
muscle coactivation. A markedly lower RFD was found in PD and the decreased RFD
correlated with reduced agonist muscle activation. Furthermore, patient RFD
correlated with the Movement-Disorder-Society-Unified-Parkinson's-Disease-Rating
Scale 3 (motor part) scores. We concluded that both knee isometric tremor
Approximate Entropy and torque steadiness clearly differentiate between patients
with PD and healthy controls. Furthermore, severely compromised RFD was found in
patients with PD and was associated with decreased agonist muscle activation.
PMID- 23155116
TI - Caution during use of desmopressin in IPSS.
PMID- 23155117
TI - Hypohydration does not alter standing balance.
AB - We examined the effect of body water deficits on standing balance and sought to
determine if plasma hyperosmolality (P(osm)) and/or volume reduction
(%DeltaV(plasma)) exerted independent effects. Nine healthy volunteers completed
three experimental trials which consisted of a euhydration (EUH) balance test, a
water deficit session and a hypohydration (HYP) balance test. Hypohydration was
achieved both by exercise-heat stress to 3% and 5% body mass loss (BML), and by a
diuretic to 3% BML. Standing balance was assessed during quiet standing on a
force platform with eyes open and closed. With eyes closed, hypohydration
significantly decreased medial-lateral sway path and velocity by 13% (both p <
.040). However, 95% confidence intervals for the mean difference between EUH and
HYP were all within the coefficient of variation of EUH measures, indicating
limited practical importance. Neither V(plasma) loss nor P(osm) increases were
associated with changes in balance. We concluded that standing balance was not
altered by hypohydration.
PMID- 23155118
TI - An alternative procedure for extraction of DNA from ancient and weathered bone
fragments.
AB - Bone is the most challenging tissue for DNA extraction and purification.
Expensive commercial kits and specific equipments are often used in forensic and
anthropology laboratories towards that goal. We present here an integrated
procedure that gives satisfactory results for DNA preparation from fresh, ancient
or weathered bones. Extraction is performed under simple but efficient vacuum
controlled conditions that greatly limit the risks of cross-contaminations. The
whole process has been designed to minimize the need for expensive equipment and
chemicals, and to be compatible with any molecular biology laboratory. In
addition, no toxic reagents are necessary and the procedure is straightforward.
Combined with quantitative polymerase chain reaction (qPCR), this method allows
species identification and sex determination from subcellular amount of DNA (1-5
pg). In addition, enough DNA is generally obtained for human DNA profiling if
necessary. The whole procedure from bone treatment to the final qPCR results
takes less than 48 hours. This procedure should allow any laboratory with
standard molecular biology equipment and expertise to perform bone DNA
characterization whenever necessary.
PMID- 23155119
TI - Decomposed and non-decomposed bodies retrieved from water: a comparative
approach.
AB - The cause and manner of death in submersion cases are a routine challenge for
forensic pathologists as they present considerable diagnostic difficulties. The
present study was undertaken with a view to determine the characteristic pattern
in bodies retrieved from water. From a total of 6779 medicolegal deaths reported
at an Apex Medical Centre, Yeotmal, a rural district of Maharashtra over a 10
year study period, only 110 cases (1.6%) were decomposed and 243 cases (3.6%)
were non-decomposed bodies retrieved from water with a rate of 0.6 decomposed
body as compared with 1.4 non-decomposed bodies per 100,000 population per year.
However, out of total 353 bodies retrieved from water, 31.2% were decomposed and
68.8% non-decomposed. Male predominance was seen in both groups with peak at 31
40 years. The cause and manner of death were ascertained as 89.9% and 82.7%,
respectively, in decomposed bodies as compared with 100% and 96.3%, respectively,
in non-decomposed bodies. Drowning was the commonest cause of death in both
groups with suicide as the commonest manner of death in decomposed bodies in
contrast to accidental in non-decomposed bodies. Excessive amount of pleural
fluid, aquatic animal activity and mud/vegetation in lower respiratory tract was
more commonly encountered in decomposed bodies. However, fine white froth was not
seen in any of the cases in contrast to 81% non-decomposed bodies. Bodies were
commonly recovered from wells in both groups. Most of the bodies were retrieved
in the rainy season followed by summer and winter seasons in both groups.
PMID- 23155121
TI - Brachytherapy using injectable seeds that are self-assembled from genetically
encoded polypeptides in situ.
AB - Brachytherapy is a common clinical technique involving implantation of sealed
radioactive "seeds" within a tumor to selectively irradiate the tumor mass while
minimizing systemic toxicity. To mitigate the disadvantages associated with
complex surgical implantation and subsequent device removal procedures, we have
developed an alternative approach using a genetically encoded peptide polymer
solution composed of a thermally responsive elastin-like polypeptide (ELP)
radiolabeled with (131)I that self-assembles into radionuclide seeds upon
intratumoral injection. The formation of these nontoxic and biodegradable polymer
seeds led to prolonged intratumoral retention (~85% ID/tumor 7 days
postinjection) of the radionuclide, elicited a tumor growth delay in 100% of the
tumors in two human xenografts (FaDu and PC-3), and cured more than 67% of tumor
bearing animals after a single administration of labeled ELP. These results
suggest that in situ self-assembly of biodegradable and injectable radionuclide
containing polypeptide seeds could be a promising therapeutic alternative to
conventional brachytherapy.
PMID- 23155122
TI - Menstrual phase and depressive symptoms differences in physiological response to
nicotine following acute smoking abstinence.
AB - INTRODUCTION: Accumulating evidence has linked depressive symptoms and sex
hormones to risk for relapse; however, the specific mechanisms involved in these
associations remain unknown. This randomized crossover study assessed
physiological response to nicotine by menstrual phase in female smokers with and
without depressive symptoms following acute smoking abstinence. METHODS: Females,
ages 18-40 years with regular menstrual cycles, not on exogenous hormones or
psychotropic medications, who reported smoking >= 5 cigarettes/day were enrolled.
Participants were stratified into 2 groups: no depressive symptoms (NDS; n = 23)
and depressive symptoms (DS; n = 24). After 4 days of biochemically verified
smoking abstinence, participants completed 2 laboratory sessions in the
follicular (F) and luteal (L) phases. Participants used nicotine nasal spray at
Time 0, and blood pressure, heart rate, and serum nicotine were measured at Time
1, 5, 10, 20, 30, 45, 60, and 90 min. RESULTS: Participants (n = 47) were 29.1 +/
6.8 years old and smoked an average of 12.5 +/- 5.1 cigarettes/day. The NDS
group had more pronounced menstrual phase differences (F > L) in diastolic blood
pressure, heart rate, and maximum concentrations of nicotine compared with the DS
group (p < .05). CONCLUSIONS: This study observed an interaction between sex
hormones and depressive symptoms such that those without depressive symptoms had
a greater menstrual phase difference in the physiological response to nicotine.
These data offer additional support for the role of sex hormones in the
physiological response to nicotine, which may play a role in menstrual phase
effects on smoking cessation.
PMID- 23155123
TI - An adenovirus-based vaccine with a double-stranded RNA adjuvant protects mice and
ferrets against H5N1 avian influenza in oral delivery models.
AB - An oral gene-based avian influenza vaccine would allow rapid development and
simplified distribution, but efficacy has previously been difficult to achieve by
the oral route. This study assessed protection against avian influenza virus
challenge using a chimeric adenovirus vector expressing hemagglutinin and a
double-stranded RNA adjuvant. Immunized ferrets and mice were protected upon
lethal challenge. Further, ferrets immunized by the peroral route induced cross
clade neutralizing antibodies, and the antibodies were selective against
hemagglutinin, not the vector. Similarly, experiments in mice demonstrated
selective immune responses against HA with peroral delivery and the ability to
circumvent preexisting vector immunity.
PMID- 23155124
TI - Clinical specificity of the enzyme immunoassay test for coccidioidomycosis varies
according to the reason for its performance.
AB - The diagnosis of coccidioidomycosis relies heavily on serologic test results in
addition to clinical history, physical examination, and radiographic findings.
Use of the enzyme immunoassay (EIA) has increased because it is rapidly performed
and does not require referral to a reference laboratory, as do complement
fixation and immunodiffusion tests. However, interpretation of immunoglobulin M
(IgM) reactivity by EIA in the absence of immunoglobulin G (IgG) reactivity has
been problematic. We conducted a retrospective medical record review of all
patients with such IgM reactivity at our institution to identify situations where
the finding was more likely to be clinically specific for coccidioidal infection.
From 1 January 2004 through 31 December 2008, a total of 1,117 patients had
positive EIA coccidioidal serology or EIA IgM-only reactivity; of these, 102
patients (9%) had EIA IgM-only reactivity. Among the 102 patients with EIA IgM
only reactivity, 60 were tested to evaluate symptomatic illness, 13 for follow-up
of previously abnormal serology, and 29 for screening purposes. Of the 102
patients, 80 (78%) had positive serologic findings by other methods or had
positive culture or histology. Fifty-four (90%) of the 60 patients whose serology
was performed to evaluate symptomatic illness had coccidioidal infection, whereas
13 (45%) of 29 patients whose serology was performed for screening purposes had
coccidioidal infection. Of the 102 patients with isolated IgM reactivity by EIA,
12 later seroconverted to IgG and IgM reactivity. The use of EIA for screening in
29 asymptomatic persons was associated with unconfirmable results in 13 (45%).
Although the majority of patients in our study with isolated IgM reactivity by
EIA had probable or confirmed coccidioidomycosis, this result must be interpreted
with caution for asymptomatic patients.
PMID- 23155125
TI - Cannabis misinterpretation and misadventure in a coroner's court.
AB - A 37-year-old, one-pack-per-day tobacco smoker collapsed and died at home. At
autopsy, he had an occluded left anterior descending coronary artery. Delta(9)
Tetrahydrocannabinol-carboxylic acid was found in his urine but no cannabinoids
were detected in his blood. Misadventure was the inquest verdict on the basis of
the urinary cannabis, with acute myocardial infarction as the primary cause and
cannabis as the secondary cause of death. Such a conclusion is a
misinterpretation of the evidence when the time duration for cannabis as a
trigger for myocardial infarction is at most two hours. The absence of cannabis
in the blood likely places the time since inhalation at more than two hours. The
role of tobacco smoking as a trigger was ignored. Cotinine, the biochemical
marker of tobacco smoke, should be added to the standard toxicological screen in
the guidelines on autopsy practice of the Royal College of Pathologists.
PMID- 23155126
TI - Platelet-rich plasma and blood components for non-transfusion use: technical and
medicolegal aspects.
AB - There are a large number of publications describing the use of platelet-rich
plasma (PRP) in multiple fields of application. These illustrate a large number
of therapeutic elements with different and specific actions within 'platelet gel'
(this term is used in the current regulations to define this product). This term,
however, lacks specificity and, depending on the method used in its production is
variable both in its blood composition and in platelet concentration, and several
publications consider better and easier methods of platelet gel production, which
may or may not lead to greater standardization in the product. The authors
illustrate the general aspects of PRP and other blood components for non
transfusion use, briefly touching on the history and different fields of
application and the rational of for its use. Given the increased use of such
preparations, the authors describe critically the regulations in force in Europe
and propose a new regulatory framework aimed to simplify and facilitate the use
of such material as a therapeutic agent within medicine.
PMID- 23155129
TI - How frequent is complete recovery after suicidal hanging?
PMID- 23155130
TI - The impact of direction of great saphenous vein total stripping on saphenous
nerve injury.
AB - OBJECTIVES: To examine and compare the effects of downwards versus upwards total
stripping of great saphenous vein (GSV) on saphenous nerve (SN) injury using
clinical and electrophysiological studies. METHODS: Fifty patients with
varicosities were equally and randomly assigned to undergo total, upwards
stripping (group A) or downwards stripping (group B) of GSV during saphenectomy.
SN function was measured with electroneurogram (ENG) before operation, two weeks
and 12 weeks after, in order to record the incidence and type of SN injury.
Clinical signs of SN injury were also recorded at the same time points. The
results were statistically analysed. RESULTS: There were no statistical
significant differences on the occurrence of SN injury between groups A and B at
two and 12 weeks, respectively, as confirmed with ENG studies and clinical
evaluation. There were no differences between the two techniques with regard to
the type of SN injury. SN injury was significantly ameliorated from 34% to 6%
during the first three months. CONCLUSION: SN injury was equally observed after
downwards or upwards total stripping of the GSV, as confirmed by ENG and clinical
evaluation, with no differences in injury type. SN injury tends to be relieved
through time in most patients.
PMID- 23155131
TI - Percutaneous transluminal angioplasty in a patient with chronic cerebrospinal
venous insufficiency and persistent left superior vena cava.
AB - Chronic cerebrospinal venous insufficiency (CCSVI) is a syndrome characterized by
stenoses of the internal jugular veins (IJVs) and/or azygos veins and formation
of collateral venous channels. A case of a 57-year-old patient with CCSVI in whom
the venous outflow from the left IJV to the right atrium occurred through a
venous anomaly, the persistent left superior vena cava (PLSVC), is reported.
PLSVC is caused by persistence of the left anterior cardinal vein that drains
blood from the limb effluent from the left and the left side of head and neck
into coronary sinus (Type a), or in the left atrium (Type b). PLSVC can be
associated either with innominate vein hypoplasia or other congenital heart
abnormalities. Because of evidence of left innominate vein hypoplasia,
angioplasty was not performed using the ordinary route but passing with the
balloon directly through the PLSVC up to the left IJV. Finally, angioplasty was
carried out in a standard manner in the right IJV as well as in the azygous vein.
Confirmation angiogram revealed complete reopening of all treated vessels with no
evidence of peri- and postoperative complications. The patient was discharged
home the following day in good general conditions. PLSVC is a rare congenital
vein anomaly but in case of concomitant innominate vein hypoplasia may prove to
be a valuable alternative to treat patients with IJV diseases.
PMID- 23155132
TI - Assessment of jugular endovascular malformations in chronic cerebrospinal venous
insufficiency: colour-Doppler scanning and catheter venography compared with
intravascular ultrasound.
AB - OBJECTIVES: Chronic cerebrospinal venous insufficiency (CCSVI) is a malformative
condition characterized by several anomalies of the azygos and/or internal
jugular veins (IJVs). Recommended diagnosis of CCSVI is performed with colour
Doppler (CD) sonography. Though catheter venography (CV) is considered as the
gold standard for determining vascular anatomy, its uniplanar point of view does
not allow an overall evaluation of endoluminal structures. This limit could be
addressed by intravascular ultrasound (IVUS). The aim of this report is to
evaluate, in patients with multiple sclerosis (MS), the accuracy of CD sonography
and CV versus IVUS in estimating the diameter and the cross-sectional area (CSA)
of the IJVs and in detecting jugular endoluminal malformations (JEM). METHOD:
Forty-five MS patients with CCSVI, diagnosed by CD sonography, were submitted to
CV during IJVs angioplasty. Twenty-five subjects were also examined with IVUS.
The IJVs maximum diameter (MAXD) and CSA were estimated. CD and CV data were
compared with IVUS data with the Bland-Altman method. RESULTS: The mean
difference in IJV MAXD recorded by CD and IVUS was -0.5 mm. The mean difference
in IJV MAXD recorded by CV and IVUS was 3.36 mm. The mean difference in IJV CSA
recorded by CD and IVUS was -11.2 mm(2). JEM recorded by IVUS were detected by CD
sonography and CV with 88% and 32% accuracy, respectively. CONCLUSIONS: CV was
significantly inferior to CD sonography and IVUS in detecting JEM. Differences
between IVUS and CD sonography in detecting JEM and in quantifying jugular
diameters were not significant. The IJV CSA was underestimated by CD sonography
compared with IVUS. CD sonography was proven to be important in the anatomical
characterization of CCSVI, providing useful information for correct intravascular
treatment.
PMID- 23155133
TI - Variability of interface pressure produced by ready-to-wear compression
stockings.
AB - PURPOSE: To assess the variability of interface pressure and changes in this
pressure over one month time interval under ready-to-use compression stockings.
METHODS: Fifteen healthy volunteers with a broad range of sizes and shapes of the
calves were included in final analysis. Each volunteer sequentially used six
pairs of stockings daily for one month each. The six pair set consisted of
stockings of three compression classes (class 1: 20-30 mmHg, class 2: 30-40 mmHg
and class 3: 40-50 mmHg), made of two materials with different stiffnesses.
Interface pressure measurements were performed at B1 point using SIGaT((r))
tester (Ganzoni-Sigvaris, St Gallen, Switzerland). Interface pressure was
measured in supine and standing positions, and during performing 10 tiptoes.
Pressure measurements were performed twice (in the morning and after using
stockings for eight hours) on the first day of using each pair of stockings, and
repeated on the 30th day. RESULTS: At the time of the first use the interface
pressure was within the range specified by the manufacturer for 160 out of 180
individual stockings. Twenty stockings (11.1%) produced interface pressure which
was 5 mmHg or more outside the range of specified compression class. In 16 of
these cases it was only one of the pair of stockings from the same box that
produced lower than specified pressure. The pressure under stockings did not
change significantly during the day. After one month the interface pressure under
the class 1 stockings decreased on average by 1.4 +/- 4.3 mmHg (P = 0.013). Class
2 and 3 stockings showed minimal pressure changes which were not statistically
significant. CONCLUSIONS: In vivo measurements of interface pressure should be a
requirement for clinical studies of compression stockings, and may be reasonable
for ensuring appropriate pressure level in clinical practice.
PMID- 23155134
TI - Endovenous laser ablation of varicose perforating veins with the 1470-nm diode
laser using the radial fibre slim.
AB - BACKGROUND: Endovenous Laser Ablation (EVLA) is one of the most accepted
treatment options for varicose veins. The aim of this study was to investigate
the efficacy and safety of the new radial fiber slim (ELVeS-radial-slim kitTM)
for the 1470 nm diode laser in perforator veins with a 1 month follow-up.
METHODS: Our prospective observational cohort study comprised 69 perforating
veins in 55 patients. Ninety percent of all patients were in the CEAP-stage C3
C6. The radial fiber slim was used to occlude the perforating vein and the great
or small saphenous vein in the same procedure. The primary efficacy endpoint of
the study was ultrasonographically proven elimination of venous reflux in the
perforating vein after at least one month. Secondary efficacy and further safety
end points after one month were as follows: (1) sonographic exclusion of
recanalization of the treated vein segments, (2) deep vein thrombosis (DVT),
clinical pulmonary embolism (PE), or superficial vein thrombosis (SVT) as defined
by objective testing, (3) death from any cause, (4) persistent clinical
complaints such as pain and paresthesia. RESULTS: Follow-up could be completed in
all patients. In all treated perforating varicose veins, occlusion with
elimination of reflux could be demonstrated immediately after the procedure.
After one month 95.6% of the treated veins were still occluded (67/69). During
follow-up, we did not diagnose any DVT, PE or SVT in the area related to the
treated perforating vein. No patient died. One patient reported paresthesia
distally of the puncture site. CONCLUSION: Endovenous laser treatment of varicose
perforating veins with 1470 nm diode laser using the radial fiber slim is
effective and safe with low recanalization rates during 1-month follow-up.
PMID- 23155135
TI - Breast MRI use uncommon among U.S. women.
AB - BACKGROUND: The goal of breast cancer screening is to reduce breast cancer
mortality. Mammography is the standard screening method for detecting breast
cancer early. Breast MRI is recommended to be used in conjunction with
mammography for screening subsets of women at high risk for breast cancer. We
offer the first study to provide national estimates of breast MRI use among women
in the United States. METHODS: We analyzed data from women who responded to
questions about having a breast MRI on the 2010 National Health Interview Survey.
We assessed report of having a breast MRI and reasons for it by sociodemographic
characteristics and access to health care and computed five-year and lifetime
breast cancer risk using the Gail model. RESULTS: Among 11,222 women who
responded, almost 5% reported ever having a breast MRI and 2% reported having an
MRI within the 2 years preceding the survey. Less than half of the women who
reported having a breast MRI were at increased risk. Approximately 60% of women
reported having the breast MRI for diagnostic reasons. Women who ever had a
breast MRI were more likely to be older, Black, and insured and to report a usual
source of health care as compared with women who reported no MRI. CONCLUSIONS:
Breast MRI use may be underused or overused in certain subgroups of women.
IMPACT: As access to health care improves, the use of breast MRI and the
appropriateness of its use for breast cancer detection will be important to
monitor.
PMID- 23155136
TI - A comparison of human papillomavirus genotype-specific DNA and E6/E7 mRNA
detection to identify anal precancer among HIV-infected men who have sex with
men.
AB - BACKGROUND: Human papillomavirus (HPV) RNA detection is reportedly more specific
for the detection of anogenital precancer than HPV DNA but it is unknown whether
this is due to detection of RNA or due to HPV genotype restriction. METHODS: A
total of 363 human immunodeficiency virus (HIV)-positive men who have sex with
men had two anal cytology samples taken and were evaluated using high-resolution
anoscopy and biopsies of visible lesions. Anal specimens were tested for E6/E7
RNA for five carcinogenic HPV genotypes (HPV16, 18, 31, 33, and 45) and tested
for the DNA of 13 carcinogenic HPV genotypes. RESULTS: DNA testing was more
likely to be positive than RNA testing (53% vs. 48%; P = 0.02) for the same five
HPV genotypes in aggregate. When restricted to five HPV genotypes targeted by the
RNA test, the sensitivity to detect anal precancer was the same for DNA and RNA
(81%), whereas RNA was more specific than DNA (65% vs. 58%; P = 0.007). In
comparison, DNA detection of all 13 carcinogenic HPV genotypes was more sensitive
(96% vs. 81%; P = 0.001) but much less specific (65% vs. 33%; P < 0.001) as
compared with RNA detection of the five HPV genotypes. CONCLUSION: After
controlling for HPV genotypes, RNA was only slightly more specific than DNA
detection for anal precancer. IMPACT: DNA or RNA testing for a subset of the most
carcinogenic HPV genotypes may be useful for distinguishing between those HPV
positive men at higher and lower risk of anal precancer and cancer.
PMID- 23155137
TI - Prospective study of HPV16 viral load and risk of in situ and invasive squamous
cervical cancer.
AB - BACKGROUND: A strong association has been shown between high viral DNA load (VL)
of human papillomavirus (HPV) type 16 and risk for cervical cancer in situ (CIS).
However, little data is available for the significance of VL in invasive squamous
cell carcinoma (SCC). METHODS: In 2 nested case-control studies among women
participating in cervical screening, with a cytologically normal first smear, we
collected 5,665 smears from 621 women with CIS, 457 with SCC, and individually
matched controls. All smears were tested for HPV, and VLs of HPV16 positive
smears were quantified using real time-PCR. The median follow-up until diagnosis
of CIS or SCC was 6.1 to 7.7 years. RESULTS: Low VL's were common among both CIS
and SCC case women, until 1 to 2 years before diagnosis when a surge in VL
occurred. The relative risk (RR) associated with low viral load of HPV16 was
around 10 for CIS, and 10 to 20 for SCC throughout 10 years before diagnosis,
compared with HPV16-negative women. For women with medium to high VL, the risk
for CIS was greatly increased from 5 years before diagnosis [RR, 19; 95%
confidence interval (CI), 7-48]. In SCC, a high VL conferred an increased risk,
but only from 3 years before diagnosis [RR, 60; 95% CI, 6-580]. CONCLUSIONS: We
show differing risk functions associated with HPV16 viral load in CIS and SCC,
respectively. We further show that viral loads were unexpectedly low early in the
SCC disease process. IMPACT: HPV16 viral load appears highly complex which may
limit its use in cervical screening.
PMID- 23155138
TI - KRAS testing and epidermal growth factor receptor inhibitor treatment for
colorectal cancer in community settings.
AB - BACKGROUND: In metastatic colorectal cancer (mCRC), mutations in the KRAS gene
predict poor response to EGF receptor (EGFR) inhibitors. Clinical treatment
guidelines now recommend KRAS testing if EGFR inhibitors are considered. Our
study investigates the clinical uptake and utilization of KRAS testing. METHODS:
We included 1,188 patients with mCRCs diagnosed from 2004 to 2009, from seven
integrated health care delivery systems with a combined membership of 5.5
million. We used electronic medical records and targeted manual chart review to
capture the complexity and breadth of real-world clinical oncology care. RESULTS:
Overall, 428 patients (36%) received KRAS testing during their clinical care, and
266 (22%) were treated with EGFR inhibitors. Age at diagnosis (P = 0.0034),
comorbid conditions (P = 0.0316), and survival time from diagnosis (P < 0.0001)
influence KRAS testing and EGFR inhibitor prescribing. The proportion who
received KRAS testing increased from 7% to 97% for those treated in 2006 and
2010, respectively, and 83% of all treated patients had a KRAS wild-type
genotype. Most patients with a KRAS mutation (86%) were not treated with EGFR
inhibitors. The interval between mCRC diagnosis and receipt of KRAS testing
decreased from 26 months (2006) to 10 months (2009). CONCLUSIONS: These findings
show rapid uptake and incorporation of this predictive biomarker into clinical
oncology care. IMPACT: In this delivery setting, KRAS testing is widely used to
guide treatment decisions with EGFR inhibitors in patients with mCRCs. An
important future research goal is to evaluate utilization of KRAS testing in
other delivery settings in the United States.
PMID- 23155139
TI - Alcohol and acetaldehyde in African fermented milk mursik--a possible etiologic
factor for high incidence of esophageal cancer in western Kenya.
AB - BACKGROUND: Esophageal cancer is unusually frequent in Western Kenya, despite the
low prevalence of classical risk factors such as heavy drinking and tobacco
smoking. Among Kenyans consumption of fermented milk is an old tradition. Our
hypothesis is that alcohol and acetaldehyde are produced during the fermentation
process and that their carcinogenic potential contributes to the high incidence
of esophageal cancer. METHODS: Eight samples of mursik milk starter cultures were
collected from different Kalenjin families in the Rift Valley province, Western
Kenya. A protocol provided by the families was used for milk fermentation.
Ethanol and acetaldehyde levels were measured by gas chromatography. The
microbial flora in starter cultures was identified by 16S and 18S sequencing.
RESULTS: 7/8 starter cultures produced mutagenic (>100 MUmol/L) levels of
acetaldehyde and 4/8 starter cultures produced more than 1,000 MUmol/L of
acetaldehyde. The highest alcohol levels (mean 79.4 mmol/L) were detected in the
four fermented milks with highest acetaldehyde production. The mean number of
microbial species in the starter cultures was 5 (range 2-8). Yeasts were
identified in all starter cultures (mean 1.5 species/milk) but their proportion
of the total microbial count varied markedly (mean 35%, range 7%-90%). A
combination of yeast and lactobacilli, especially Candida krusei with
Lactobacillus kefiri, with the exclusion of other species, seemed to correlate
with higher acetaldehyde and ethanol levels. CONCLUSIONS: Significant levels of
ethanol and acetaldehyde were produced during mursik fermentation. IMPACT: When
ingested several times daily the repeated exposure to carcinogenic levels of
acetaldehyde may contribute to esophageal carcinogenesis.
PMID- 23155140
TI - Excessive fibrin deposition in nasal polyps caused by fibrinolytic impairment
through reduction of tissue plasminogen activator expression.
AB - RATIONALE: Nasal polyps (NPs) are characterized by intense edema or formation of
pseudocysts filled with plasma proteins, mainly albumin. However, the mechanisms
underlying NP retention of plasma proteins in their submucosa remain unclear.
OBJECTIVES: We hypothesized that formation of a fibrin mesh retains plasma
proteins in NPs. We assessed the fibrin deposition and expression of the
components of the fibrinolytic system in patients with chronic rhinosinusitis
(CRS). METHODS: We assessed fibrin deposition in nasal tissue from patients with
CRS and control subjects by means of immunofluorescence. Fibrinolytic components,
d-dimer, and plasminogen activators were measured using ELISA, real-time PCR, and
immunohistochemistry. We also performed gene expression and protein
quantification analysis in cultured airway epithelial cells. MEASUREMENTS AND
MAIN RESULTS: Immunofluorescence data showed profound fibrin deposition in NP
compared with uncinate tissue (UT) from patients with CRS and control subjects.
Levels of the cross-linked fibrin cleavage product protein, d-dimer, were
significantly decreased in NP compared with UT from patients with CRS and control
subjects, suggesting reduced fibrinolysis (P < 0.05). Expression levels of tissue
plasminogen activator (t-PA) mRNA and protein were significantly decreased in NP
compared with UT from patients with CRS and control subjects (P < 0.01).
Immunohistochemistry demonstrated clear reduction of t-PA in NP, primarily in the
epithelium and glands. Th2 cytokine-stimulated cultured airway epithelial cells
showed down-regulation of t-PA, suggesting a potential Th2 mechanism in NP.
CONCLUSIONS: A Th2-mediated reduction of t-PA might lead to excessive fibrin
deposition in the submucosa of NP, which might contribute to the tissue
remodeling and pathogenesis of CRS with nasal polyps.
PMID- 23155141
TI - Endothelial progenitor cells in acute myocardial infarction and sleep-disordered
breathing.
AB - RATIONALE: Mobilization and functions of endothelial progenitor cells (EPCs) are
increased in patients with acute myocardial infarction (AMI). Yet, sleep
disordered breathing (SDB) is highly prevalent in patients with AMI. OBJECTIVES:
To compare EPC numbers and functions in patients with AMI with SDB (AMI-SDB) and
without SDB (AMI-only) and to determine the effects of intermittent hypoxia (IH)
in vitro on EPC proliferative and angiogenic properties. METHODS: Forty male
patients with AMI underwent a whole-night sleep study using ambulatory
monitoring. Nineteen had SDB (oxygen desaturation index > 5 events/h). AMI-SDB
and AMI-only patients were matched by age, body mass index, blood chemistry, and
comorbidities. Blood samples were analyzed by flow cytometry, endothelial cell
colony-forming units (EC-CFU), paracrine measures, blood chemistry, and oxidative
stress, inflammatory, and angiogenic markers. Effects of IH in vitro were studied
in 12 healthy subjects. MEASUREMENTS AND MAIN RESULTS: Circulating EPCs
(CD34(+)/KDR(+)), angiogenic T cells (CD3(+)/CD31(+)/CXCR4(+)), and vascular
endothelial growth factor in monocytes were significantly higher in AMI-SDB
patients, whereas plasma stromal cell-derived factor (SDF)-1alpha levels were
significantly lower. Also, EC-CFU numbers and EC-CFU paracrine effects on
endothelial tube formation were significantly higher in AMI-SDB compared with AMI
only patients. Similarly, in cell cultures from healthy subjects, EC-CFU numbers
and their paracrine effects on endothelial tube formation were increased after
exposure to IH in vitro compared with normoxia. CONCLUSIONS: Coexistent mild to
moderate SDB in patients with AMI increased the mobilization, proliferative and
angiogenic capacities of EPCs, angiogenic T-cell numbers, and vascular
endothelial growth factor expression in monocytes compared with patients with AMI
without SDB. IH in vitro had similar effects on healthy EPC functions.
PMID- 23155143
TI - The interplay between the effects of lifetime asthma, smoking, and atopy on fixed
airflow obstruction in middle age.
AB - RATIONALE: The contribution by asthma to the development of fixed airflow
obstruction (AO) and the nature of its effect combined with active smoking and
atopy remain unclear. OBJECTIVES: To investigate the prevalence and relative
influence of lifetime asthma, active smoking, and atopy on fixed AO in middle
age. METHODS: The population-based Tasmanian Longitudinal Health Study cohort
born in 1961 (n = 8,583) and studied with prebronchodilator spirometry in 1968
was retraced (n = 7,312) and resurveyed (n = 5,729 responses) from 2002 to 2005.
A sample enriched for asthma and chronic bronchitis underwent a further
questionnaire, pre- and post-bronchodilator spirometry (n = 1,389), skin prick
testing, lung volumes, and diffusing capacity measurements. Prevalence estimates
were reweighted for sampling fractions. Multiple linear and logistic regression
were used to assess the relevant associations. MEASUREMENTS AND MAIN RESULTS:
Main effects and interactions between lifetime asthma, active smoking, and atopy
as they relate to fixed AO were measured. The prevalence of fixed AO was 6.0%
(95% confidence interval [CI], 4.5-7.5%). Its association with early-onset
current clinical asthma was equivalent to a 33 pack-year history of smoking (odds
ratio, 3.7; 95% CI, 1.5-9.3; P = 0.005), compared with a 24 pack-year history for
late-onset current clinical asthma (odds ratio, 2.6; 95% CI, 1.03-6.5; P =
0.042). An interaction (multiplicative effect) was present between asthma and
active smoking as it relates to the ratio of post-bronchodilator FEV(1)/FVC, but
only among those with atopic sensitization. CONCLUSIONS: Active smoking and
current clinical asthma both contribute substantially to fixed AO in middle age,
especially among those with atopy. The interaction between these factors provides
another compelling reason for atopic individuals with current asthma who smoke to
quit.
PMID- 23155144
TI - Stakeholder priorities for comparative effectiveness research in chronic
obstructive pulmonary disease: a workshop report.
AB - Comparative effectiveness research (CER) is intended to address the expressed
needs of patients, clinicians, and other stakeholders. Representatives of 54
stakeholder groups with an interest in chronic obstructive pulmonary disease
(COPD) participated in workshops convened by the COPD Outcomes-based Network for
Clinical Effectiveness and Research Translation (CONCERT) over a 2-year period.
Year 1 focused on chronic care and care coordination. Year 2 focused on acute
care and transitions in care between healthcare settings. Discussions and
provisional voting were conducted via teleconferences and e-mail exchanges before
the workshop. Final prioritization votes occurred after in-person discussions at
the workshop. We used a modified Delphi approach to facilitate discussions and
consensus building. To more easily quantify preferences and to evaluate the
internal consistency of rankings, the Analytic Hierarchy Process was incorporated
in Year 2. Results of preworkshop and final workshop voting often differed,
suggesting that prioritization efforts relying solely on requests for topics from
stakeholder groups without in-person discussion may provide different research
priorities. Research priorities varied across stakeholder groups, but generally
focused on studies to evaluate different approaches to healthcare delivery (e.g.,
spirometry for diagnosis and treatment, integrated healthcare strategies during
transitions in care) rather than head-to-head comparisons of medications. This
research agenda may help to inform groups intending to respond to CER funding
opportunities in COPD. The methodologies used, detailed in the online supplement,
may also help to inform prioritization efforts for CER in other health
conditions.
PMID- 23155142
TI - Pulmonary vascular complications of liver disease.
AB - Hepatopulmonary syndrome and portopulmonary hypertension are two pulmonary
vascular complications of liver disease. The pathophysiology underlying each
disorder is distinct, but patients with either condition may be limited by
dyspnea. A careful evaluation of concomitant symptoms, the physical examination,
pulmonary function testing and arterial blood gas analysis, and
echocardiographic, imaging, and hemodynamic studies is crucial to establishing
(and distinguishing) these diagnoses. Our understanding of the pathobiology,
natural history, and treatment of these disorders has advanced considerably over
the past decade; however, the presence of either still increases the risk of
morbidity and mortality in patients with underlying liver disease. There is no
effective medical treatment for hepatopulmonary syndrome. Although liver
transplantation can resolve hepatopulmonary syndrome, there appears to be worse
survival even with transplantation. Liver transplantation poses a very high risk
of death in those with significant portopulmonary hypertension, where targeted
medical therapies may improve functional status and allow successful
transplantation in a small number of select patients.
PMID- 23155146
TI - Association between obstructive sleep apnea and cancer incidence in a large
multicenter Spanish cohort.
AB - RATIONALE: Obstructive sleep apnea (OSA) has been associated with increased
cancer mortality, but whether it is also associated with cancer incidence is
unknown. OBJECTIVES: To investigate whether OSA is associated with increased
cancer incidence in a large clinical cohort. METHODS: A multicenter, clinical
cohort study including consecutive patients investigated for suspected OSA
between 2003 and 2007 in seven Spanish teaching hospitals. Apnea-hypopnea index
(AHI) and percent nighttime with oxygen saturation less than 90% (TSat(90)) were
used as surrogates of OSA severity, both as continuous variables and categorized
by tertiles. Cox proportional hazards regression analyses were used to calculate
hazard ratio (HR) and 95% confidence interval (CI) for cancer incidence after
adjusting for confounding variables. MEASUREMENTS AND MAIN RESULTS: A total of
4,910 patients were analyzed (median follow-up, 4.5 yr; interquartile range, 3.4
5.2). Compared with the lower TSat(90) category (<1.2%), the adjusted hazards
(95% CI) of cancer incidence for increasing categories were 1.58 (1.07-2.34) for
TSat(90) 1.2-12% and 2.33 (1.57-3.46) for TSat(90) greater than 12%. Continuous
TSat(90) was also associated with cancer incidence (adjusted HR, 1.07 [1.02-1.13]
per 10-unit increase in TSat(90)). In stratified analyses, TSat(90) was
associated with cancer incidence in patients younger than 65 years (adjusted HR,
1.13 [95% CI, 1.06-1.21] per 10-unit increase in TSat(90)) and males (adjusted
HR, 1.11 [95% CI, 1.04-1.17] per 10-unit increase in TSat(90)). AHI was not
associated with cancer incidence in the adjusted analyses, except for patients
younger than 65 years (adjusted HR for AHI >43 vs. <18.7, 1.66; 95% CI, 1.04
2.64). CONCLUSIONS: Increased overnight hypoxia as a surrogate of OSA severity
was associated with increased cancer incidence. This association seems to be
limited to men and patients younger than 65 years of age.
PMID- 23155147
TI - Carbapenem-sparing antibiotic regimens for infections caused by Klebsiella
pneumoniae carbapenemase-producing K. pneumoniae in intensive care unit.
AB - A carbapenem-sparing regimen of tigecycline plus gentamicin or colistin was
effective for treating 24 of 26 (92%) Klebsiella pneumoniae carbapenemase
producing K. pneumoniae infectious episodes in 22 polytrauma intensive care unit
patients without comorbidities. The 30-day crude mortality rate was 14%. Regimens
were considered appropriate in 12% of episodes according to the Vitek 2 System
and in 100% based on E-test.
PMID- 23155148
TI - Facing ubiquitous viruses: when hand washing is not enough.
PMID- 23155145
TI - Extracorporeal membrane oxygenation for pandemic influenza A(H1N1)-induced acute
respiratory distress syndrome: a cohort study and propensity-matched analysis.
AB - RATIONALE: Many patients with severe acute respiratory distress syndrome (ARDS)
caused by influenza A(H1N1) infection receive extracorporeal membrane oxygenation
(ECMO) as a rescue therapy. OBJECTIVES: To analyze factors associated with death
in ECMO-treated patients and the influence of ECMO on intensive care unit (ICU)
mortality. METHODS: Data from patients admitted for H1N1-associated ARDS to
French ICUs were prospectively collected from 2009 to 2011 through the national
REVA registry. We analyzed factors associated with in-ICU death in ECMO
recipients, and the potential benefit of ECMO using a propensity score-matched
(1:1) cohort analysis. MEASUREMENTS AND MAIN RESULTS: A total of 123 patients
received ECMO. By multivariate analysis, increasing values of age, lactate, and
plateau pressure under ECMO were associated with death. Of 103 patients receiving
ECMO during the first week of mechanical ventilation, 52 could be matched to non
ECMO patients of comparable severity, using a one-to-one matching and using
control subjects only once. Mortality did not differ between the two matched
cohorts (odds ratio, 1.48; 95% confidence interval, 0.68-3.23; P = 0.32).
Interestingly, the 51 ECMO patients who could not be matched were younger, had
lower Pa(o(2))/Fi(o(2)) ratio, had higher plateau pressure, but also had a lower
ICU mortality rate than the 52 matched ECMO patients (22% vs. 50%; P < 0.01).
CONCLUSIONS: Under ECMO, an ultraprotective ventilation strategy minimizing
plateau pressure may be required to improve outcome. When patients with severe
influenza A(H1N1)-related ARDS treated with ECMO were compared with
conventionally treated patients, no difference in mortality rates existed. The
unmatched, severely hypoxemic, and younger ECMO-treated patients had, however, a
lower mortality.
PMID- 23155149
TI - Epidemiology of invasive pneumococcal disease among high-risk adults since the
introduction of pneumococcal conjugate vaccine for children.
AB - BACKGROUND: Certain chronic diseases increase risk for invasive pneumococcal
disease (IPD) and are indications for receipt of 23-valent pneumococcal
polysaccharide vaccine (PPV23). Since the pediatric introduction of 7-valent
pneumococcal conjugate vaccine (PCV7) in 2000, incidence of IPD among adults has
declined. The relative magnitude of these indirect effects among persons with and
without PPV23 indications is unknown. METHODS: We evaluated IPD incidence among
adults with and without PPV23 indications using population- and laboratory-based
data collected during 1998-2009 and estimates of the denominator populations with
PPV23 indications from the National Health Interview Survey. We compared rates
before and after PCV7 use by age, race, PPV23 indication, and serotype. RESULTS:
The proportion of adult IPD cases with PPV23 indications increased from 51%
before to 61% after PCV7 introduction (P < .0001). PCV7-serotype IPD declined
among all race, age, and PPV23 indication strata, ranging from 82% to 97%.
Overall IPD rates declined in most strata, by up to 65%. However, incidence
remained highest among adults with PPV23 indications compared with those without
(34.9 vs 8.8 cases per 100 000 population, respectively). Apart from age >=65
years, diabetes is now the most common indication for PPV23 (20% of all cases vs
10% of cases in 1998-1999). CONCLUSIONS: Although IPD rates have declined among
adults, adults with underlying conditions remain at increased risk of IPD and
comprise a larger proportion of adult IPD cases in 2009 compared with 2000. A
continued increase in the prevalence of diabetes among US adults could lead to
increased burden of pneumococcal disease.
PMID- 23155150
TI - Performances of prognostic scoring systems in patients with healthcare-associated
pneumonia.
AB - BACKGROUND: There are limited data on the performance of the pneumonia severity
index (PSI) and CURB-65 (confusion, urea, respiratory rate, blood pressure, age
>=65) score, which were originally developed for community-acquired pneumonia
(CAP), for patients with healthcare-associated pneumonia (HCAP). METHODS: The
performances of PSI and CURB-65 were retrospectively evaluated in patients with
HCAP compared to patients with CAP using prospectively collected data between
January 2008 and December 2010. RESULTS: In total, 938 patients hospitalized with
pneumonia were eligible for this study, consisting of 519 (55%) with CAP and 419
(45%) with HCAP. The PSI and CURB-65 scores had similar trends of increasing
mortality with worsening risk class in both the HCAP and CAP groups. In the HCAP
group, however, the low-risk patients identified using CURB-65 had a higher
aggregate 30-day mortality compared with the low-risk patients identified using
PSI. Although the performances of PSI and CURB-65 in the HCAP group showed
similar trends to those observed in the CAP group, the estimated areas under the
receiver operating characteristic curve for PSI (0.679, 95% confidence interval
[CI], .619-.739) and CURB-65 (0.599, 95% CI, .522-.675) in the HCAP group were
significantly lower than those in the CAP group (0.835, 95% CI, .768-.759 for PSI
and .686-.832 for CURB-65). CONCLUSIONS: The performances of PSI and CURB-65 for
predicting 30-day mortality in patients with HCAP were comparable to those in
patients with CAP. However, the discriminatory powers of PSI and CURB-65 for 30
day mortality were significantly lower in the HACP group than those in the CAP
group.
PMID- 23155152
TI - Three-dimensional modelling of the venous system by direct multislice helical
computed tomography venography: technique, indications and results.
AB - The aim of multislice helical computed tomography venography (CTV) is to provide
a precise, global and three-dimensional (3D) anatomical depiction of the venous
network of the lower limbs. A multislice and multidetector spiral CT acquisition
of the lower limbs with contrast injection of the dorsal foot produces about 1000
slices in 30 seconds. Dedicated volume-rendering software can compute a realistic
and interactive 3D model of the venous system in realtime. This new tool
furnishes an accurate 3D representation of the whole venous system of the lower
limb with a realistic 3D model of the limbs, providing a road map of the varicose
networks complementary to the duplex ultrasound (DUS). CTV allows a complete
morphological study of the deep veins, including the detection of anatomical
variations and proximal venous obstruction, not easily detectable by DUS. In the
case of deep vein thrombosis, it has been shown to be a good diagnostic tool,
well correlated with sonography. It also demonstrates, in some cases,
haemodynamic patterns which are not available by DUS, particularly for perforator
veins and congenital vascular malformations. The use of virtual reality
techniques enables a complete anatomical study of both deep and superficial veins
including a virtual dissection of the limbs. CTV is also a great educational tool
to learn anatomy of the venous system and a powerful research tool to improve our
knowledge of venous anatomy.
PMID- 23155151
TI - Pharmacokinetic interactions between the hepatitis C virus protease inhibitor
boceprevir and ritonavir-boosted HIV-1 protease inhibitors atazanavir, darunavir,
and lopinavir.
AB - BACKGROUND: Boceprevir represents a new treatment option for hepatitis C (HCV)
infected patients, including those with HCV/human immunodeficiency virus
coinfection; however, little is known about pharmacokinetic interactions between
boceprevir and antiretroviral drugs. METHODS: A randomized, open-label study to
assess the pharmacokinetic interactions between boceprevir and ritonavir-boosted
protease inhibitors (PI/r) was conducted in 39 healthy adults. Subjects received
boceprevir (800 mg, 3 times daily) for 6 days and then received PI/r as follows:
atazanavir (ATV) 300 mg once daily, lopinavir (LPV) 400 mg twice daily, or
darunavir (DRV) 600 mg twice daily, each with ritonavir (RTV) 100 mg on days 10
31, plus concomitant boceprevir on days 25-31. RESULTS: Boceprevir decreased the
exposure of all PI/r, with area under the concentration-time curve [AUC] from
time 0 to the time of the last measurable sample geometric mean ratios of 0.65
(90% confidence interval [CI], .55-.78) for ATV/r; 0.66 (90% CI, .60-.72) for
LPV/r, and 0.56 (90% CI, .51-.61) for DRV/r. Coadministration with boceprevir
decreased RTV AUC during a dosing interval tau (AUC(tau)) by 22%-36%. ATV/r did
not significantly affect boceprevir exposure, but boceprevir AUC(tau) was reduced
by 45% and 32% when coadministered with LPV/r and DRV/r, respectively. Overall,
treatments were well tolerated with no unexpected adverse events. CONCLUSIONS:
Concomitant administration of boceprevir with PI/r resulted in reduced exposures
of PI and boceprevir. These drug-drug interactions may reduce the effectiveness
of PI/r and/or boceprevir when coadministered.
PMID- 23155153
TI - Diagnostic tests (2) - positive and negative predictive values.
PMID- 23155154
TI - Additional information and comments to the article review citing CHIVA.
PMID- 23155157
TI - A future forum for UK occupational health?
PMID- 23155158
TI - Judith Leyster the young flute player 1635.
PMID- 23155159
TI - The human spirit level.
PMID- 23155160
TI - Why I became an occupational physician...
PMID- 23155162
TI - Vaccinating welders against pneumonia.
PMID- 23155164
TI - Comments on Sancini et al.
PMID- 23155165
TI - Charmed to be sure.
PMID- 23155166
TI - How I use it: social bookmarking.
PMID- 23155168
TI - Wide propagation of graded signals in nonspiking neurons.
AB - Signal processing in neuritic trees is ruled by the concerted action of passive
and active membrane properties that, together, determine the degree of electrical
compartmentalization of these trees. We analyzed how active properties modulate
spatial propagation of graded signals in a pair of nonspiking (NS) neurons of the
leech. NS neurons present a very extensive neuritic tree that mediates the
interaction with all the excitatory motoneurons in leech ganglia. NS cells
express voltage-activated Ca(2+) conductances (VACCs) that, under certain
experimental conditions, evoke low-threshold spikes. We studied the distribution
of calcium transients in NS neurons loaded with fluorescent calcium probes in
response to low-threshold spikes, electrical depolarizing pulses, and synaptic
inputs. The three types of stimuli evoked calcium transients of similar
characteristics in the four main branches of the neuron. The magnitude of the
calcium transients evoked by electrical pulses was a graded function of the
change in NS membrane potential and depended on the baseline potential level. The
underlying VACCs were partially inactivated at rest and strongly inactivated at
20 mV. Stimulation of mechanosensory pressure cells evoked calcium transients in
NS neurons whose amplitude was a linear function of the amplitude of the
postsynaptic response. The results evidenced that VACCs aid an efficient
propagation of graded signals, turning the vast neuritic tree of NS cells into an
electrically compact structure.
PMID- 23155169
TI - Hemispheric differences in the control of limb dynamics: a link between arm
performance asymmetries and arm selection patterns.
AB - Human handedness has been described and measured from two perspectives:
handedness inventories rate hand preferences, whereas other tests examine motor
performance asymmetries. These two measurement approaches reflect a major
controversy in a literature that defines handedness as either a preference or an
asymmetry in sensorimotor processing. Over the past decade, our laboratory has
developed a model of handedness based on lateralization of neural processes. This
model attributes distinct control processes to each hemisphere, which in turn
lead to observable interlimb sensorimotor performance asymmetries. We now
hypothesize that arm preference, or choice, may depend on the interaction between
sensorimotor performance asymmetries and the given task. The purpose of this
study is to examine whether arm selection is linked to interlimb performance
asymmetries during reaching. Right-handed subjects made choice and nonchoice
reaches to each of eight targets (d = 3.5 cm) arranged radially (r = 13 cm)
around a midline starting position. We displaced each cursor (one associated with
each hand) 30 cm to the midline start circle to ensure that there were no
hemispace-related geometric, mechanical, or perceptual biases to use either arm
for the two midline targets. The three targets on each side of the midline
received mostly reaches from the ipsilateral arm, a tendency previously described
as a "hemispace bias." However, the midline targets, which were equidistant from
each hand, received more dominant arm reaches. Dominant arm hand paths to these
targets were straighter and more accurately directed. Inverse dynamics analyses
revealed a more proficient dominant arm strategy that exploited intersegmental
dynamics to a greater extent than did the nondominant arm. These findings suggest
that sensorimotor asymmetries in dynamic coordination might explain limb choices.
We discuss the implications of these results for theories of action selection,
models of handedness, and models of neural lateralization.
PMID- 23155170
TI - Cooling reduces the cutaneous afferent firing response to vibratory stimuli in
glabrous skin of the human foot sole.
AB - Skin on the foot sole plays an important role in postural control. Cooling the
skin of the foot is often used to induce anesthesia to determine the role of skin
in motor and balance control. The effect of cooling on the four classes of
mechanoreceptor in the skin is largely unknown, and thus the aim of the present
study was to characterize the effects of cooling on individual skin receptors in
the foot sole. Such insight will better isolate individual receptor contributions
to balance control. Using microneurography, we recorded 39 single nerve afferents
innervating mechanoreceptors in the skin of the foot sole in humans. Afferents
were identified as fast-adapting (FA) or slowly adapting (SA) type I or II (FA I
n = 16, FA II n = 7, SA I n = 6, SA II n = 11). Receptor response to vibration
was compared before and after cooling of the receptive field (2-20 min). Overall,
firing response was abolished in 30% of all receptors, and this was equally
distributed across receptor type (P = 0.69). Longer cooling times were more
likely to reduce firing response below 50% of baseline; however, some afferent
responses were abolished with shorter cooling times (2-5 min). Skin temperature
was not a reliable indicator of the level of receptor activation and often became
uncoupled from receptor response levels, suggesting caution in the use of this
parameter as an indicator of anesthesia. When cooled, receptors preferentially
coded lower frequencies in response to vibration. In response to a sustained
indentation, SA receptors responded more like FA receptors, primarily coding "on
off" events.
PMID- 23155171
TI - Circuit mechanisms revealed by spike-timing correlations in macaque area MT.
AB - We recorded simultaneously from pairs of motion-sensitive neurons in the middle
temporal cortex (MT) of macaque monkeys and used cross-correlations in the timing
of spikes between neurons to gain insights into cortical circuitry. We
characterized the time course and stimulus dependency of the cross-correlogram
(CCG) for each pair of neurons and of the auto-correlogram (ACG) of the
individual neurons. For some neuron pairs, the CCG showed negative flanks that
emerged next to the central peak during stimulus-driven responses. Similar
negative flanks appeared in the ACG of many neurons. Negative flanks were most
prevalent and deepest when the neurons were driven to high rates by visual
stimuli that moved in the neurons' preferred directions. The temporal development
of the negative flanks in the CCG coincided with a parallel, modest reduction of
the noise correlation between the spike counts of the neurons. Computational
analysis of a model cortical circuit suggested that negative flanks in the CCG
arise from the excitation-triggered mutual cross-inhibition between pairs of
excitatory neurons. Intracortical recurrent inhibition and afterhyperpolarization
caused by intrinsic outward currents, such as the calcium-activated potassium
current of small conductance, can both contribute to the negative flanks in the
ACG. In the model circuit, stronger intracortical inhibition helped to maintain
the temporal precision between the spike trains of pairs of neurons and led to
weaker noise correlations. Our results suggest a neural circuit architecture that
can leverage activity-dependent intracortical inhibition to adaptively modulate
both the synchrony of spike timing and the correlations in response variability.
PMID- 23155172
TI - Movement representation in the primary motor cortex and its contribution to
generalizable EMG predictions.
AB - It is well known that discharge of neurons in the primary motor cortex (M1)
depends on end-point force and limb posture. However, the details of these
relations remain unresolved. With the development of brain-machine interfaces
(BMIs), these issues have taken on practical as well as theoretical importance.
We examined how the M1 encodes movement by comparing single-neuron and
electromyographic (EMG) preferred directions (PDs) and by predicting force and
EMGs from multiple neurons recorded during an isometric wrist task. Monkeys moved
a cursor from a central target to one of eight peripheral targets by exerting
force about the wrist while the forearm was held in one of two postures. We fit
tuning curves to both EMG and M1 activity measured during the hold period, from
which we computed both PDs and the change in PD between forearm postures
(DeltaPD). We found a unimodal distribution of these DeltaPDs, the majority of
which were intermediate between the typical muscle response and an unchanging,
extrinsic coordinate system. We also discovered that while most neuron-to-EMG
predictions generalized well across forearm postures, end-point force measured in
extrinsic coordinates did not. The lack of force generalization was due to
musculoskeletal changes with posture. Our results show that the dynamics of most
of the recorded M1 signals are similar to those of muscle activity and imply that
a BMI designed to drive an actuator with dynamics like those of muscles might be
more robust and easier to learn than a BMI that commands forces or movements in
external coordinates.
PMID- 23155173
TI - Network interneurons underlying ciliary locomotion in Hermissenda.
AB - In the nudibranch mollusk Hermissenda, ciliary locomotion contributes to the
generation of two tactic behaviors. Light elicits a positive phototaxis, and
graviceptive stimulation evokes a negative gravitaxis. Two classes of light
responsive premotor interneurons in the network contributing to ciliary
locomotion have been recently identified in the cerebropleural ganglia.
Aggregates of type I interneurons receive monosynaptic excitatory (I(e)) or
inhibitory (I(i)) input from identified photoreceptors. Type II interneurons
receive polysynaptic excitatory (II(e)) or inhibitory (II(i)) input from
photoreceptors. The ciliary network also includes type III inhibitory (III(i))
interneurons, which form monosynaptic inhibitory connections with ciliary
efferent neurons (CENs). Illumination of the eyes evokes a complex inhibitory
postsynaptic potential, a decrease of I(i) spike activity, a complex excitatory
postsynaptic potential, and an increase of I(e) spike activity. Here, we
characterized the contribution of identified I, II, and III(i) interneurons to
the neural network supporting visually guided locomotion. In dark-adapted
preparations, light elicited an increase in the tonic spike activity of II(e)
interneurons and a decrease in the tonic spike activity of II(i) interneurons.
Fluorescent dye-labeled type II interneurons exhibited diverse projections within
the circumesophageal nervous system. However, a subclass of type II interneurons,
II(e(cp)) and II(i(cp)) interneurons, were shown to terminate within the
ipsilateral cerebropleural ganglia and indirectly modulate the activity of CENs.
Type II interneurons form monosynaptic or polysynaptic connections with
previously identified components of the ciliary network. The identification of a
monosynaptic connection between I(e) and III(i) interneurons shown here suggest
that they provide a major role in the light-dependent modulation of CEN spike
activity underlying ciliary locomotion.
PMID- 23155174
TI - Blinks slow memory-guided saccades.
AB - Memory-guided saccades are slower than visually guided saccades. The usual
explanation for this slowing is that the absence of a visual drive reduces the
discharge of neurons in the superior colliculus. We tested a related hypothesis:
that the slowing of memory-guided saccades was due also to the more frequent
occurrence of gaze-evoked blinks with memory-guided saccades compared with
visually guided saccades. We recorded gaze-evoked blinks in three monkeys while
they performed visually guided and memory-guided saccades and compared the
kinematics of the different saccade types with and without blinks. Gaze-evoked
blinks were more common during memory-guided saccades than during visually guided
saccades, and the well-established relationship between peak and average velocity
for saccades was disrupted by blinking. The occurrence of gaze-evoked blinks was
associated with a greater slowing of memory-guided saccades compared with
visually guided saccades. Likewise, when blinks were absent, the peak velocity of
visually guided saccades was only slightly higher than that of memory-guided
saccades. Our results reveal interactions between circuits generating saccades
and blink-evoked eye movements. The interaction leads to increased curvature of
saccade trajectories and a corresponding decrease in saccade velocity. Consistent
with this interpretation, the amount of saccade curvature and slowing increased
with gaze-evoked blink amplitude. Thus, although the absence of vision decreases
the velocity of memory-guided saccades relative to visually guided saccades
somewhat, the cooccurrence of gaze-evoked blinks produces the majority of slowing
for memory-guided saccades.
PMID- 23155175
TI - Local inhibition modulates learning-dependent song encoding in the songbird
auditory cortex.
AB - Changes in inhibition during development are well documented, but the role of
inhibition in adult learning-related plasticity is not understood. In songbirds,
vocal recognition learning alters the neural representation of songs across the
auditory forebrain, including the caudomedial nidopallium (NCM), a region
analogous to mammalian secondary auditory cortices. Here, we block local
inhibition with the iontophoretic application of gabazine, while simultaneously
measuring song-evoked spiking activity in NCM of European starlings trained to
recognize sets of conspecific songs. We find that local inhibition differentially
suppresses the responses to learned and unfamiliar songs and enhances spike-rate
differences between learned categories of songs. These learning-dependent
response patterns emerge, in part, through inhibitory modulation of selectivity
for song components and the masking of responses to specific acoustic features
without altering spectrotemporal tuning. The results describe a novel form of
inhibitory modulation of the encoding of learned categories and demonstrate that
inhibition plays a central role in shaping the responses of neurons to learned,
natural signals.
PMID- 23155176
TI - Critical role of trkB receptors in reactive axonal sprouting and
hyperexcitability after axonal injury.
AB - Traumatic brain injury (TBI) causes many long-term neurological complications.
Some of these conditions, such as posttraumatic epilepsy, are characterized by
increased excitability that typically arises after a latent period lasting from
months to years, suggesting that slow injury-induced processes are critical. We
tested the hypothesis that trkB activation promotes delayed injury-induced
hyperexcitability in part by promoting reactive axonal sprouting. We modeled
penetrative TBI with transection of the Schaffer collateral pathway in knock-in
mice having an introduced mutation in the trkB receptor (trkB(F616A)) that
renders it susceptible to inhibition by the novel small molecule 1NMPP1. We
observed that trkB activation was increased in area CA3 1 day after injury and
that expression of a marker of axonal growth, GAP43, was increased 7 days after
lesion. Extracellular field potentials in stratum pyramidale of area CA3 in acute
slices from sham-operated and lesioned mice were normal in control saline.
Abnormal bursts of population spikes were observed under conditions that were
mildly proconvulsive but only in slices taken from mice lesioned 7-21 days
earlier and not in slices from control mice. trkB activation, GAP43 upregulation,
and hyperexcitability were diminished by systemic administration of 1NMPP1 for 7
days after the lesion. Synaptic transmission from area CA3 to area CA1 recovered
7 days after lesion in untreated mice but not in mice treated with 1NMPP1. We
conclude that trkB receptor activation and reactive axonal sprouting are critical
factors in injury-induced hyperexcitability and may contribute to the
neurological complications of TBI.
PMID- 23155177
TI - Roles for substance P and gastrin-releasing peptide as neurotransmitters released
by primary afferent pruriceptors.
AB - Recent studies support roles for neurokinin-1 (NK-1) and gastrin-releasing
peptide (GRP) receptor-expressing spinal neurons in itch. We presently
investigated expression of substance P (SP) and GRP in pruritogen-responsive
primary sensory neurons and roles for these neuropeptides in itch signaling.
Responses of dorsal root ganglion (DRG) cells to various pruritogens were
observed by calcium imaging. DRG cells were then processed for SP, GRP, and
isolectin B-4 (IB4; a marker for nonpeptidergic neurons) immunofluorescence. Of
pruritogen-responsive DRG cells, 11.8-26.8%, 21.8-40.0%, and 21.4-26.8% were
immunopositive for SP, GRP, and IB4, respectively. In behavioral studies, both
systemic and intrathecal administration of a NK-1 receptor antagonist
significantly attenuated scratching evoked by chloroquine and a protease
activated receptor 2 agonist, SLIGRL, but not histamine, bovine adrenal medulla
peptide 8-22 (BAM8-22), or serotonin. Systemic or intrathecal administration of a
GRP receptor antagonist attenuated scratching evoked by chloroquine and SLIGRL
but not BAM8-22 or histamine. The GRP receptor antagonist enhanced scratching
evoked by serotonin. These results indicate that SP and GRP expressed in primary
sensory neurons are partially involved as neurotransmitters in histamine
independent itch signaling from the skin to the spinal cord.
PMID- 23155179
TI - Relationship between electrophysiological signature and defined sensory modality
of trigeminal ganglion neurons in vivo.
AB - The trigeminal ganglia (TG) innervate a heterogeneous set of highly sensitive and
exposed tissues. Weak, innocuous stimuli can evoke pain as a normal response in
some areas such as the cornea. This observation implies, however, the capability
of low-threshold mechanoreceptors, inducing pain in the normal condition. To
clarify this matter, the present study correlates the electrical signature (both
fiber conduction velocity and somatic electrical properties) with receptor field,
mechanical threshold, and temperature responsiveness of sensory afferents
innervating tissues with dissimilar sensitivity (skin vs. cornea) in the
trigeminal domain. Intracellular recordings were obtained in vivo from 148
neurons of the left TG of 62 mice. In 111 of these neurons, the peripheral
receptor field was successfully localized: 96 of them innervated the hairy skin,
while the remaining 15 innervated the cornea. The electrical signature was
defined and peripheral responses correlated with tissue target. No high threshold
neurons were found in the cornea. Moreover, the electrical signature of corneal
afferents resembles nociceptive neurons in the skin. TG skin afferents showed
similar membrane electrical signature and sensory modality as skin afferents from
dorsal root ganglion, although TG afferents exhibited a shorter duration of
afterhyperpolarization then those previously described in dorsal root ganglion.
These data suggest than new or different ways to classify and study TG sensory
neurons may be required.
PMID- 23155178
TI - Alterations in upper limb muscle synergy structure in chronic stroke survivors.
AB - Previous studies in neurologically intact subjects have shown that motor
coordination can be described by task-dependent combinations of a few muscle
synergies, defined here as a fixed pattern of activation across a set of muscles.
Arm function in severely impaired stroke survivors is characterized by
stereotypical postural and movement patterns involving the shoulder and elbow.
Accordingly, we hypothesized that muscle synergy composition is altered in
severely impaired stroke survivors. Using an isometric force matching protocol,
we examined the spatial activation patterns of elbow and shoulder muscles in the
affected arm of 10 stroke survivors (Fugl-Meyer <25/66) and in both arms of six
age-matched controls. Underlying muscle synergies were identified using non
negative matrix factorization. In both groups, muscle activation patterns could
be reconstructed by combinations of a few muscle synergies (typically 4). We did
not find abnormal coupling of shoulder and elbow muscles within individual muscle
synergies. In stroke survivors, as in controls, two of the synergies were
comprised of isolated activation of the elbow flexors and extensors. However,
muscle synergies involving proximal muscles exhibited consistent alterations
following stroke. Unlike controls, the anterior deltoid was coactivated with
medial and posterior deltoids within the shoulder abductor/extensor synergy and
the shoulder adductor/flexor synergy in stroke was dominated by activation of
pectoralis major, with limited anterior deltoid activation. Recruitment of the
altered shoulder muscle synergies was strongly associated with abnormal task
performance. Overall, our results suggest that an impaired control of the
individual deltoid heads may contribute to poststroke deficits in arm function.
PMID- 23155180
TI - Association between 2 angiographic subtypes of renal artery fibromuscular
dysplasia and clinical characteristics.
AB - BACKGROUND: Initially based on histology, the diagnosis of renal artery
fibromuscular dysplasia (FMD) is now based mostly on angiographic appearance
because arterial tissue samples are rarely available. This retrospective cross
sectional study aimed to assess the clinical relevance of a binary angiographic
classification of FMD lesions (unifocal or multifocal) based on computed
tomographic or magnetic resonance angiography. METHODS AND RESULTS: Adult
patients diagnosed with FMD in a single tertiary care center for hypertension
management were identified by screening of electronic files. FMD lesions were
reviewed and classified according to computed tomography or magnetic resonance
angiography as multifocal if there were at least 2 stenoses in the same arterial
segment; otherwise, they were classified as unifocal. Of 337 patients with
established renal artery FMD, 276 (82%) were classified as multifocal. Patients
with unifocal and multifocal lesions differed significantly in median age at
diagnosis of FMD (30 and 49 years) and hypertension (26 and 40 years), sex
distribution (female:male ratio, 2:1 and 5:1), initial blood pressure (157/97 and
146/88 mm Hg), current smoking (50% and 26%), prevalence of unilateral renal
artery lesions (79% and 38%), presence of kidney asymmetry (33% and 10%), renal
revascularization procedures (90% and 35%), and hypertension cure rates in
patients who underwent revascularization (54% and 26%). CONCLUSIONS: A binary
angiographic classification into unifocal or multifocal renal artery FMD is
straightforward and discriminates 2 groups of patients with different clinical
phenotypes.
PMID- 23155181
TI - Cytochrome P450 subfamily 2J polypeptide 2 expression and circulating
epoxyeicosatrienoic metabolites in preeclampsia.
AB - BACKGROUND: Preeclampsia is a multisystem disorder of pregnancy, originating in
the placenta. Cytochrome P450 (CYP)-dependent eicosanoids regulate vascular
function, inflammation, and angiogenesis, which are mechanistically important in
preeclampsia. METHODS AND RESULTS: We performed microarray screening of placenta
and decidua (maternal placenta) from 25 preeclamptic women and 23 control
subjects. The CYP subfamily 2J polypeptide 2 (CYP2J2) was upregulated in
preeclamptic placenta and decidua. Reverse-transcription polymerase chain
reaction confirmed the upregulation, and immunohistochemistry localized CYP2J2 in
trophoblastic villi and deciduas at 12 weeks and term. The CYP2J2 metabolites,
5,6-epoxyeicosatrienoic acid (EET), 14,15-EET, and the corresponding
dihydroxyeicosatrienoic acids, were elevated in preeclamptic women compared with
controls in the latter two thirds of pregnancy and after delivery. Stimulating a
trophoblast-derived cell line with the preeclampsia-associated cytokine tumor
necrosis factor-alpha enhanced CYP2J2 gene and protein expression. In 2
independent rat models of preeclampsia, reduced uterine-perfusion rat and the
transgenic angiotensin II rat, we observed elevated EET, dihydroxyeicosatrienoic
acid, and preeclamptic features that were ameliorated by the CYP epoxygenase
inhibitor N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MsPPOH).
Uterine arterial rings of these rats also dilated in response to MsPPOH.
Furthermore, 5,6-EET could be metabolized to a thromboxane analog. In a bioassay,
5,6-EET increased the beating rate of neonatal cardiomyocytes. Blocking
thromboxane synthesis reversed that finding and also normalized large-conductance
calcium-activated potassium channel activity. CONCLUSIONS: Our data implicate
CYP2J2 in the pathogenesis of preeclampsia and as a potential candidate for the
disturbed uteroplacental remodeling, leading to hypertension and endothelial
dysfunction.
PMID- 23155182
TI - Variation in psychosis gene ZNF804A is associated with a refined schizotypy
phenotype but not neurocognitive performance in a large young male population.
AB - Genetic variability within the ZNF804A gene has been recently found to be
associated with schizophrenia and bipolar disorder, although the pathways by
which this gene may confer risk remain largely unknown. We set out to investigate
whether common ZNF804A variants affect psychosis-related intermediate phenotypes
such as cognitive performance dependent on prefrontal and frontotemporal brain
function, schizotypal traits, and attenuated psychotic experiences in a large
young male population. Association analyses were performed using all 4 available
self-rated schizotypy questionnaires and cognitive data retrospectively drawn
from the Athens Study of Psychosis Proneness and Incidence of Schizophrenia
(ASPIS). DNA samples from 1507 healthy young men undergoing induction to military
training were genotyped for 4 previously studied polymorphic markers in the
ZNF804A gene locus. Single-marker analysis revealed significant associations
between 2 recently identified candidate schizophrenia susceptibility variants
(rs1344706 and rs7597593) and a refined positive schizotypy phenotype
characterized primarily by self-rated paranoia/ideas of reference. Nominal
associations were noted with all positive, but not negative, schizotypy related
factors. ZNF804A genotype effect on paranoia was confirmed at the haplotype
level. No significant associations were noted with central indexes of sustained
attention or working memory performance. In this study, ZNF804A variation was
associated with a population-based self-rated schizotypy phenotype previously
suggested to preferentially reflect genetic liability to psychosis and defined by
a tendency to misinterpret otherwise neutral social cues and perceptual
experiences in one's immediate environment, as personally relevant and
significant information. This suggests a novel route by which schizophrenia
implicated ZNF804A genetic variation may confer risk to clinical psychosis at the
general population level.
PMID- 23155183
TI - Neurophysiological evidence of corollary discharge function during vocalization
in psychotic patients and their nonpsychotic first-degree relatives.
AB - Predictions about sensations resulting from motor acts are instantiated through
neural mechanisms such as the corollary discharge. With each action, the
corollary discharge provides an unconscious comparison between predicted and
actual sensations resulting from the action; closer matches result in greater
suppression of sensation. This mechanism is disrupted in schizophrenia (SZ) and
may contribute to, or reflect a failure to, distinguish self- from externally
generated experiences, a hallmark of psychosis. We asked whether disruption is
specific to SZ or is seen in other psychotic illnesses and in first-degree
relatives of psychotic patients. Corollary discharge function was assessed in SZ
patients (n = 30), schizoaffective (SA) patients (n = 19), bipolar patients with
a history of psychosis (BPP; n = 39), nonpsychotic relatives of SZ (n = 30), SA
(n = 23), and BPP (n = 50) patients, and healthy controls (n = 43). The N1
component of the event-related potential, reflecting auditory cortical responses
to sounds, was elicited by speech sound onset as subjects talked and later when
they listened to a recording of those sounds. N1 was suppressed during talking
compared to N1 during listening, consistent with the suppressive action of the
corollary discharge mechanism. Suppression was significantly reduced in SZ and
BPP patients, with a similar trend in the smaller SA group. Patient groups did
not differ, and unaffected relatives did not differ from controls or probands.
The failure to monitor sensations resulting from self-generated actions,
implicating corollary discharge dysfunction, may be a common feature across
affective and nonaffective psychosis. Data from unaffected family members do not
indicate that this is a marker of psychosis risk.
PMID- 23155184
TI - Diabetes or prediabetes in newly diagnosed patients with nonaffective psychosis?
A historical and contemporary view.
PMID- 23155186
TI - Brentuximab vedotin.
AB - Brentuximab vedotin (SGN-35), an intravenously administered CD30-specific
antibody-drug conjugate, has recently been approved by the U.S. Food and Drug
Administration for two indications, including (i) patients with Hodgkin lymphoma
relapsing after autologous stem-cell transplantation (ASCT), or after two
multidrug regimens in patients with Hodgkin lymphoma who are not candidates for
ASCT; and (ii) patients with systemic anaplastic large cell lymphoma (ALCL) who
failed at least one prior multidrug chemotherapy regimen. Patients with Hodgkin
lymphoma and ALCL treated with brentuximab vedotin showed markedly high response
rates for a single agent, exceeding 70% and 80% for Hodgkin lymphoma and ALCL,
respectively. The complete response rate was equally as impressive, at 34% and
57% for Hodgkin lymphoma and ALCL, respectively. Results like these and from many
other upcoming clinical trials, in which brentuximab vedotin is being
investigated in the frontline setting, promise to profoundly change how we manage
the CD30-positive lymphoproliferative malignancies. The mechanism of action,
preclinical antitumor activity, and clinical activity of brentuximab vedotin
against Hodgkin lymphoma, ALCL, and other CD30-expressing lymphomas are reviewed.
PMID- 23155185
TI - Targeted delivery of paclitaxel to EphA2-expressing cancer cells.
AB - PURPOSE: YSA is an EphA2-targeting peptide that effectively delivers anticancer
agents to prostate cancer tumors. Here, we report on how we increased the drug
like properties of this delivery system. EXPERIMENTAL DESIGN: By introducing non
natural amino acids, we have designed two new EphA2 targeting peptides: YNH,
where norleucine and homoserine replace the two methionine residues of YSA, and
dYNH, where a D-tyrosine replaces the L-tyrosine at the first position of the YNH
peptide. We describe the details of the synthesis of YNH and dYNH paclitaxel
conjugates (YNH-PTX and dYNH-PTX) and their characterization in cells and in
vivo. RESULTS: dYNH-PTX showed improved stability in mouse serum and
significantly reduced tumor size in a prostate cancer xenograft model and also
reduced tumor vasculature in a syngeneic orthotopic allograft mouse model of
renal cancer compared with vehicle or paclitaxel treatments. CONCLUSION: This
study reveals that targeting EphA2 with dYNH drug conjugates could represent an
effective way to deliver anticancer agents to a variety of tumor types.
PMID- 23155187
TI - Inside the black box: starting to uncover the underlying decision rules used in a
one-by-one expert assessment of occupational exposure in case-control studies.
AB - OBJECTIVES: Evaluating occupational exposures in population-based case-control
studies often requires exposure assessors to review each study participant's
reported occupational information job-by-job to derive exposure estimates.
Although such assessments likely have underlying decision rules, they usually
lack transparency, are time consuming and have uncertain reliability and
validity. We aimed to identify the underlying rules to enable documentation,
review and future use of these expert-based exposure decisions. METHODS:
Classification and regression trees (CART, predictions from a single tree) and
random forests (predictions from many trees) were used to identify the underlying
rules from the questionnaire responses, and an expert's exposure assignments for
occupational diesel exhaust exposure for several metrics: binary exposure
probability and ordinal exposure probability, intensity and frequency. Data were
split into training (n=10 488 jobs), testing (n=2247) and validation (n=2248)
datasets. RESULTS: The CART and random forest models' predictions agreed with 92
94% of the expert's binary probability assignments. For ordinal probability,
intensity and frequency metrics, the two models extracted decision rules more
successfully for unexposed and highly exposed jobs (86-90% and 57-85%,
respectively) than for low or medium exposed jobs (7-71%). CONCLUSIONS: CART and
random forest models extracted decision rules and accurately predicted an
expert's exposure decisions for the majority of jobs, and identified
questionnaire response patterns that would require further expert review if the
rules were applied to other jobs in the same or different study. This approach
makes the exposure assessment process in case-control studies more transparent,
and creates a mechanism to efficiently replicate exposure decisions in future
studies.
PMID- 23155188
TI - Pattern and predictors for respiratory illnesses and symptoms and lung function
among textile workers in Karachi, Pakistan.
AB - OBJECTIVES: To determine pattern and predictors for respiratory illnesses and
symptoms and lung function among textile workers in Karachi, Pakistan. METHODS:
This was a cross-sectional survey of 372 adult male textile workers from the
spinning and weaving sections of 15 textile mills from Karachi. Data were
collected from November to December 2009 through a structured, pretested
questionnaire and spirometry. RESULTS: Prevalence of byssinosis was 10.5%,
chronic cough 7.5%, chronic phlegm 12.9%, wheeze with shortness of breath 22.3%,
shortness of breath (grade 2) 21%, chest tightness ever 33.3%; whereas, a low
prevalence of asthma (4%) was identified in this population. Eight per cent had
obstructive, 8% restrictive and 2% mixed pattern of lung function abnormality.
After controlling for potential confounders, work in the spinning section
predicts frequent wheeze (AOR=2.0; 95% CI 1.1 to 3.5), wheeze with shortness of
breath (AOR=1.8; 95% CI 1.0 to 3.4), and obstructive pattern on spirometry
(AOR=2.5; 95% CI 1.0 to 6.2). Prolonged duration of work predicts breathlessness
grade 1 (AOR=1.8; 95% CI 1.0 to 3.1) and grade 2 (AOR=2.7; 95% CI 1.3 to 5.4), as
well as decrements in Forced Expiratory Volume in the first second (FEV(1)) and
FEV(1)/Forced Vital Capacity ratio. Lack of education predicts frequent wheeze
(AOR=2.0; 95% CI 1.2 to 3.3), and Sindhi ethnicity predicts chest tightness apart
from during cold (AOR=2.7; 95% CI 1.1 to 6.6). CONCLUSIONS: This study highlights
the burden of respiratory illnesses and symptoms, and a low prevalence of asthma
among textile workers in Karachi. Work in the spinning section, lack of
education, prolonged duration of work and Sindhi ethnicity, were identified as
important risk factors.
PMID- 23155189
TI - Household solid fuel use and pulmonary function in an urban population in
Shanghai, China.
AB - OBJECTIVES: We examined the association between household solid fuel exposure and
lung function in a densely populated district in urban Shanghai, China. METHODS:
Spirometry was performed in 12 506 subjects, aged 18 and over, residing in the
Putuo District in Shanghai, China, in a cross-sectional survey. Exposure to solid
fuel use at home was assessed by an administered questionnaire, estimating
duration and total amount of solid fuel use at home during the lifetime. RESULTS:
After adjusting for confounders, the subjects with exposure to household solid
fuel had a 1.3% (95% CI 0.57 to 2.02) decrease in forced expiratory volume in 1 s
(FEV(1)) percent predicted and 3.5% (95% CI 2.74 to 4.18) decrease in forced
vital capacity (FVC) percent predicted, respectively. Trends towards decreased
pulmonary function measures were seen for longer duration and greater amount of
household fuel use at home, in the highest compared with lowest tertile (p values
for trend <0.001). We observed decrease in FEV(1) and FVC percent predicted
across increase in tertile of body mass index in association with in-home solid
fuel exposure. CONCLUSIONS: This study suggests that in-home solid fuel exposure
is associated with reduced lung function in an urban population.
PMID- 23155190
TI - Random effects regression models for trends in standardised mortality ratios.
AB - OBJECTIVES: Standardised mortality ratios (SMRs) play an important role in the
epidemiological literature, particularly in evaluations of occupational hazards.
While some authors have argued that comparisons of SMRs should be avoided, many
investigators find such analyses appealing particularly when data are sparse. For
example, calendar period-specific SMRs often are examined to identify emerging
problems or to assess whether a hazard that impacted death rates in the past has
abated. However, because the distribution of people with respect to age usually
changes as calendar time advances, comparisons of SMRs across calendar periods
can produce misleading results. METHODS: We propose a random effects model to
reduce the potential bias arising from comparisons of SMRs. This approach is
illustrated using data from a study of workers employed at the Department of
Energy's Oak Ridge National Laboratory. RESULTS: When there is homogeneity across
strata of covariates in the ratio of death rates in the target population to that
in the reference population, the proposed model yields results equivalent to
those obtained by a classical analysis of SMRs. However, as evidence against such
homogeneity increases, the model yields a random effects version of SMRs for
which patterns will conform better to those obtained from an internal analysis of
rate ratios. CONCLUSIONS: The proposed random effects model can reduce potential
bias arising in the comparisons of SMRs.
PMID- 23155191
TI - Migraine and restless legs syndrome in men.
AB - BACKGROUND: Previous studies suggest an association between migraine and restless
legs syndrome (RLS). Population-based data, however, have been limited to women.
The aim of this study is to evaluate the association between migraine and RLS in
a male cohort. METHODS: We conducted a cross-sectional study among 22,926
participants in the Physicians' Health Study. Migraine and RLS information was
self-reported. RLS was classified according to four minimal diagnostic criteria.
Age- and multivariable-adjusted logistic regression models were calculated.
RESULTS: Of the 22,926 participants (mean age 67.8), 2816 (12.3%) reported
migraine and 1717 (7.5%) RLS. Migraine was associated with an increased
multivariable-adjusted odds ratio (OR) (95% confidence interval (CI)) of 1.20
(1.04-1.38) for having RLS. The association remained stable after excluding men
with potential mimics of RLS and was not modified by age. CONCLUSIONS: Results of
our study indicate an association between migraine and RLS in men. The magnitude
of effect is similar to what has been reported in women.
PMID- 23155192
TI - Continuing on . . . Hemicrania continua.
PMID- 23155193
TI - NXN-188, a selective nNOS inhibitor and a 5-HT1B/1D receptor agonist, inhibits
CGRP release in preclinical migraine models.
AB - BACKGROUND: NXN-188 is a combined neuronal nitric oxide synthase (nNOS) inhibitor
and 5-hydroxytryptamine 1B/1D (5-HT1B/1D) receptor agonist. Using preclinical
models, we evaluated whether these two unique therapeutic principles have a
synergistic effect in attenuating stimulated calcitonin gene-related peptide
(CGRP) release, a marker of trigeminal activation. METHODS: We examined the
effect of NXN-188 on: (1) KCl-, capsaicin- and resiniferatoxin (RTX)-induced
immunoreactive CGRP (iCGRP) release from isolated preparation of rat dura mater,
trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC); and (2) capsaicin
and electrical stimulation (ES)-induced middle meningeal artery (MMA) dilation
in a rat closed-cranial window. RESULTS: NXN-188 inhibited: (1) KCl-stimulated
iCGRP release from dura mater (% decrease mean +/- SEM, lowest effective
concentration) (35 +/- 6%, 30 uM), TG (24 +/- 11%, 10 uM) and TNC (40 +/- 8%, 10
uM); (2) capsaicin- and RTX-induced iCGRP release from dura mater; and (3)
capsaicin- and ES-induced increase in dural artery diameter (32 +/- 5%, 3 mg kg(
1) intravenous (i.v.) and 36 +/- 1%, 10 mg kg(-1) i.v.). CONCLUSIONS: NXN-188
inhibits CGRP release from migraine-relevant cephalic tissues. Its effect is most
likely mediated via a combination of nNOS-inhibition and 5-HT1B/1D receptor
agonism in dura mater while the mechanisms of action for inhibition of CGRP
release from TG and TNC have to be investigated further.
PMID- 23155194
TI - Are children still at risk for lead poisoning?
AB - BACKGROUND: The prevalence of elevated blood lead levels (EBLLs) has decreased
nationally, creating challenges in identifying children at risk. METHODS: In a
community known to have lead hazards, we screened children with a field
administered capillary blood lead test and asked parents to complete a
questionnaire about lead risk factors. RESULTS: Of the 77 child-parent pairs
screened with a blood lead test and a parental questionnaire, 4 had finger stick
blood lead levels of >=10 ug/dL. Of these, one child had a confirmatory venous
blood lead level >10 ug/dL (1.3%; 95% CI = 0.0%-4.7%), which is near the US
prevalence but less than the historic prevalence for this region. A median of 2
risk factors for each of the environmental, behavioral, and knowledge/awareness
domains were noted. CONCLUSIONS: Despite a low prevalence of children with EBLL,
parental report suggested that approximately 29% of children had lead-based paint
in their home environment.
PMID- 23155195
TI - Outcomes of children treated with tracheostomy and positive-pressure ventilation
at home.
AB - BACKGROUND: Long-term outcomes for children who survive on tracheostomy and
positive-pressure ventilation (TPPV) at home are not well known. METHODS: A
retrospective review of 20 years of clinical data at a single institution was
performed. Outcome measures included 5-year survival, decannulation rate, and
neurocognition. RESULTS: A total of 91 children were categorized under neuromotor
dysfunction (52%), chronic lung disease (29%), and congenital anomalies (20%).
The 5-year survival rates for these categories were 89% (95% confidence interval
[CI] = 80%-99%), 76% (95% CI = 57%-100%), and 94% (95% CI = 83%-100%),
respectively. Overall, the 5-year decannulation rate was 25% (95% CI = 14%-35%),
with children with chronic lung disease having the highest rate (51%). It was
found that 14% were extremely delayed in neurocognition. CONCLUSION: Most
children on TPPV at home survive beyond 5 years, and a significant number are
decannulated. Primary care physicians and communities should be prepared to
accommodate the increasing number of children on TPPV at home.
PMID- 23155196
TI - New-style liquid detergent packs present new danger to children.
PMID- 23155197
TI - Major depression and first-time hospitalization with ischemic heart disease,
cardiac procedures and mortality in the general population: a retrospective
Danish population-based cohort study.
AB - OBJECTIVE: We investigated the association between unipolar depression and
incident hospital admissions due to ischemic heart disease, invasive cardiac
procedures and mortality independent of other medical illnesses. METHODS: A
population-based cohort of 4.6 million persons aged 15 years or older and born in
Denmark was followed up from 1995-2009. Incidence rate ratio (IRR) and mortality
rate ratio (MRR) were estimated by survival analysis, stratified by or adjusted
for gender, age, severe chronic somatic comorbidity and calendar time. RESULTS:
Adjusted risks of cardiac hospital admissions and death were significantly
increased by up to 15% and 68%, respectively, in persons with hospital admissions
due to depression, and were most increased in 15-59 year old women (IRR: 1.64;
MRR: 2.57) and men with depression (IRR: 1.39; MRR: 2.21), and during the first
180 days after being diagnosed with depression (women: IRR: 1.38; MRR: 2.35; men:
IRR: 1.42; MRR: 2.67). One-year mortality after new ischemic heart disease was
elevated by 34% in women and men. By contrast, overall rates of invasive cardiac
procedures following cardiac hospitalizations were significantly decreased by 34%
in persons with depression but were twofold increased in men recently diagnosed
with depression. CONCLUSION: Clinical depression leading to hospitalization was a
risk factor for new cardiac complications independent of somatic comorbidity in
the magnitude of other cardiac risk factors, particularly in individuals between
15-59 years of age and during the first weeks following psychiatric admission.
Our findings support recent cardiovascular disease prevention guidelines on
assessing depression among other psychosocial factors in patients at increased
cardiovascular disease (CVD) risk.
PMID- 23155198
TI - Polychlorinated biphenyls impair blood-brain barrier integrity via disruption of
tight junction proteins in cerebrum, cerebellum and hippocampus of female Wistar
rats: neuropotential role of quercetin.
AB - Polychlorinated biphenyls (PCBs) comprise a ubiquitous class of toxic substances
associated with carcinogenic and tumor-promoting effects as well as neurotoxic
properties. Reactive oxygen species, which is produced from PCBs, alters blood
brain barrier (BBB) integrity, which is paralleled by cytoskeletal rearrangements
and redistribution and disappearance of tight junction proteins (TJPs) like
claudin-5 and occludin. Quercetin, a potent antioxidant present in onion and
other vegetables, appears to protect brain cells against oxidative stress, a
tissue-damaging process associated with Alzheimer's and other neurodegenerative
disorders. The aim of this study is to analyze the role of quercetin on oxidative
stress markers and transcription of transmembrane and cytoplasmic accessory TJPs
on cerebrum, cerebellum and hippocampus of female rats exposed to PCBs. Rats were
divided into the following four groups. Group I: received only vehicle (corn oil)
intraperitoneally (i.p.); group II: received Aroclor 1254 at a dose of 2 mg/kg
body weight (bwt)/day (i.p); group III: received Aroclor 1254 (i.p.) and
simultaneously quercetin 50 mg/kg bwt/day through gavage and group IV: received
quercetin alone gavage. From the experiment, the levels of hydrogen peroxide,
lipid peroxidation and thiobarbituric acid reactive substances were observed to
increase significantly in cerebrum, cerebellum and hippocampus as 50%, 25% and
20%, respectively, after exposure to PCB, and the messenger RNA expression of TJP
in rats exposed to PCBs is decreased and is retrieved to the normal level
simultaneously in quercetin-treated rats. Hence, quercetin can be used as a
preventive medicine to PCBs exposure and prevents neurodegenerative disorders.
PMID- 23155199
TI - Effect of lifestyles on the blood mercury level in Korean adults.
AB - Mercury (Hg) is widely distributed in the environment and oral exposure is a main
route in the general population. In this study, we estimated the dietary intake
of Hg and its relationship with blood Hg levels in Korean adults. The study
subjects were recruited from three different districts (rural: 189, coastal: 208
and urban: 184). We used a general questionnaire to collect information about
demographic factors, lifestyles and diet. Dietary habits were studied using the
24-h recall method. The estimation of Hg intake was performed using the database
of Hg contents in 128 Korean foods based on the previous studies. Blood Hg was
analyzed using Direct Mercury Analyzer with the gold-amalgam method. Daily intake
of Hg by diet was estimated at 13.57 MUg (0.22 MUg/kg body weight). The geometric
mean Hg concentration in whole blood was 3.92 MUg/L. Blood Hg level and Hg intake
by diet was higher in coastal areas than in urban or rural areas, respectively.
Blood Hg level correlated with the intake of Hg consumed from diet. Seafood was
highly responsible and account for 75.6% of total dietary Hg intake. In this
study, blood Hg concentrations were found to be significantly affected by sex,
age, individual lifestyles and especially the amount of seafood intake, which
might play an important role in determining blood Hg levels in Korean adults.
PMID- 23155200
TI - Protective effects of resveratrol on sepsis-induced DNA damage in the lymphocytes
of rats.
AB - Sepsis, often initiated by an infection, is a state of disrupted inflammatory
homeostasis. There is increasing evidence that oxidative stress has an important
role in the development of sepsis-induced multiorgan failure. Resveratrol (RV) is
a polyphenolic compound found in the skin of red fruits, such as mulberries and
red grapes, and in peanuts. RV has been reported to have an antioxidant,
antiproliferative, and anti-inflammatory properties in various models. It has
also been found to inhibit the proliferation of a variety of human cancer cell
lines, including breast, prostate, colon, pancreatic, and thyroid. This study has
been undertaken to assess the role of RV on the sepsis-induced oxidative DNA
damage in the lymphocytes of Wistar albino rats by the standard and
formamidopyrimidine DNA glycosylase (Fpg)-modified comet assays. The parameters
of tail length, tail intensity, and tail moment were evaluated for the
determination of DNA damage. According to the study, the DNA damage was found to
be significantly higher in the sepsis-induced rats when compared with the control
rats (p < 0.05). The parameters were significantly decreased in the RV-treated
sepsis-induced group when compared with the sepsis-induced group. The parameters
in the sepsis-induced rats were found to be significantly higher in the Fpg
modified comet assay when compared with the standard comet assay (p < 0.05), and
RV treatment decreases the DNA damage in the sepsis-induced rats, suggesting that
the oxidative stress is likely to be responsible for DNA damage and RV might have
a role in the prevention of sepsis-induced oxidative DNA damage.
PMID- 23155201
TI - The scintigraphic evaluation and genetic correlation of joint involvements in
pediatric patients with familial Mediterranean fever.
AB - PURPOSE: We aimed to evaluate the articular involvements in pediatric patients
with familial Mediterranean fever (FMF) with joint symptoms by bone scintigraphy
and to correlate the involved joints with the gene mutations. MATERIALS AND
METHODS: A total of 41 newly diagnosed patients in pediatric age group (28 girls
and 13 boys; mean age 9.14 +/- 2.91 years) with joint involvement symptoms were
included in this study. Scintigraphic images were obtained at 5th min (blood pool
or early phase) and starting at 3 h (late phase) after (after tracer injection)
intravenous administration of technetium-99m (99mTc)-methylendiphosphonate (MDP).
Genomic DNA was isolated from leukocytes using standard salting out procedure.
The sequencing data were analyzed. RESULTS: Of the 41 patients, arthritis was
found in 21 (51.2%) patients. Of the 21 patients, there was single joint
involvement in 15 (71.4%) patients and multiple joint involvement in six (28.6%)
patients. The mean age of patients with joint involvement (8 +/- 2.3 years) were
considerably lower than the patients without joint involvement (10.35 +/- 3.04
years), and this was statistically significant (p = 0.008). The most commonly
involved joints were ankles and knees. Multiple joint involvements were most
frequently observed in the M694V and M694I gene mutations (16.7%). CONCLUSIONS:
We use and recommend the bone scintigraphy in patients with FMF to determine the
presence and distribution of arthritis, since bone scintigraphy is inexpensive,
noninvasive, easy-to-use, and also is more sensitive in the diagnosis and
distribution of arthritis than conventional radiological methods and clinical
examination.
PMID- 23155202
TI - Influence of coadministration of artemether and lumefantrine on selected plasma
biochemical and erythrocyte oxidative stress indices in female Wistar rats.
AB - Among the artemisinin-based combination therapy (ACT) regimens, artemisinin
derivative, artemether in combination with lumefantrine (artemether-lumefantrine,
AL) has achieved excellent results in the fight against malarial scourge. In this
study, we evaluated the toxic potential of these drugs at the therapeutic doses
in female Wistar rats. Animals were randomly divided into four groups: those
administered 1% Tween 80 (control), those administered artemether (4 mg/kg body
weight), those administered lumefantrine (24 mg/kg body weight), and those
coadministered artemether (4 mg/kg body weight) and lumefantrine (24 mg/kg body
weight). The drugs were orally administered twice daily for 3 days by gastric
intubation after which selected plasma biochemical indices, and erythrocytes
antioxidant defence and lipid peroxidation markers were evaluated.
Coadministration of artemether and lumefantrine raised liver and renal function
markers and increased atherogenic index. While reduced glutathione, glucose-6
phosphate dehydrogenase (G6PD) and catalase activities were reduced, glutathione
peroxidase and glutathione-s-transferase activities increased in all the treated
groups compared to the control group. The drugs caused significant (p < 0.05)
elevation of malondialdehyde (MDA) levels compared to the control group. These
results imply that coadministration of artemether and lumefantrine may increase
the risks of atherosclerosis as well as liver and renal function impairments in
the users. In addition, the drugs may also promote oxidative stress in the
erythrocytes.
PMID- 23155203
TI - Coma blisters in children: case report and review of the literature.
AB - Coma-induced blisters is a rare condition associated with prolonged impairment of
conscious level, which is relatively well-known in adults following overdose with
barbiturates. However, it has been very rarely described in children. A case of
coma-bullae occurring in an 11-year-old child with meningoencephalitis is herein
reported. The bullous lesions occurred on the limbs and trunks, and evolved into
necrotic ulcers in a few days. No correlation with any drug overdosage was found.
A skin biopsy revealed epidermal and eccrine sweat gland necrosis with abundant
neutrophils, and thrombosis of the vessels in the lower dermis. A comprehensive
review of the literature showed that only 5 cases of coma-bullae in children have
been published so far. Coma blistering resolves spontaneously within days or
weeks. Diagnosis of coma-bullae may require careful clinical-pathologic
correlation to exclude other blistering diseases in children.
PMID- 23155204
TI - White matter changes in an untreated, newly diagnosed case of classical
homocystinuria.
AB - The authors report the case of a 4-year-old boy who developed progressive
unilateral weakness and developmental delays prior to his diagnosis of classical
homocystinuria. Magnetic resonance imaging (MRI) of the brain demonstrated
diffuse white matter changes, raising the concern for a secondary diagnosis
causing leukoencephalopathy, since classical homocystinuria is not typically
associated with these changes. Other inborn errors of the transsulfuration
pathway have been reported as causing these changes. Once begun on therapy for
his homocystinuria, his neurologic deficits resolved and his delays rapidly
improved. Repeat MRI performed one year after instating therapy showed resolution
of his white matter abnormalities. This case illustrates the need to consider
homocystinuria and other amino acidopathies in the differential diagnosis of
childhood white matter diseases and lends weight to the hypothesis that
hypermethioninemia may induce white matter changes.
PMID- 23155205
TI - Childhood polyarteritis nodosa presenting with central nervous system
manifestations and the posterior reversible encephalopathy syndrome.
AB - Polyarteritis nodosa is a systemic necrotizing vasculitis involving medium-sized
muscular arteries. Polyneuropathy is the only neurologic manifestation included
in the pediatric classification schema. Central nervous system manifestations
include infarction, hemorrhage, and encephalitis. We report on a 13-year-old
female whose initial presentation of polyarteritis nodosa included hypertension,
seizures, and neuroimaging findings of vasogenic edema and posterior reversible
encephalopathy syndrome. Posterior reversible encephalopathy syndrome has been
reported in association with renal disease, transplantation, autoimmunity, and
cytotoxic medications. Posterior reversible encephalopathy syndrome outcomes are
usually favorable with supportive care and treatment of the underlying etiology.
The patient's neurologic condition improved after treatment of hypertension.
Hypertension, posterior reversible encephalopathy syndrome, and abdominal pain
led to a diagnostic workup. A systemic vasculitis was confirmed after detection
of a perinephric hematoma and intrarenal aneurysms. This is a novel case of
posterior reversible encephalopathy syndrome as an initial manifestation of
pediatric polyarteritis nodosa.
PMID- 23155206
TI - Cognitive impairment occurs in children and adolescents with multiple sclerosis:
results from a United States network.
AB - In the largest sample studied to date, we measured cognitive functioning in
children and adolescents with pediatric multiple sclerosis (n = 187) as well as
those with clinically isolated syndrome (n = 44). Participants were consecutively
enrolled from six United States Pediatric Multiple Sclerosis Centers of
Excellence. Participants had a mean of 14.8 +/- 2.6 years of age and an average
disease duration of 1.9 +/- 2.2 years. A total of 65 (35%) children with multiple
sclerosis and 8 (18%) with clinically isolated syndrome met criteria for
cognitive impairment. The most frequent areas involved were fine motor
coordination (54%), visuomotor integration (50%), and speeded information
processing (35%). A diagnosis of multiple sclerosis (odds ratio = 3.60,
confidence interval = 1.07, 12.36, P = .04) and overall neurologic disability
(odds ratio = 1.47, confidence interval = 1.10, 2.10, P = .03) were the only
independent predictors of cognitive impairment. Cognitive impairment may occur
early in these patients, and prompt recognition is critical for their care.
PMID- 23155207
TI - Phenotype-based care in chronic obstructive pulmonary disease.
PMID- 23155208
TI - Systemic inflammation in patients with chronic obstructive pulmonary disease: one
size no longer fits all!
PMID- 23155209
TI - Socioeconomic barriers to lung transplantation: balancing access and equity.
PMID- 23155210
TI - Hermansky-Pudlak syndrome interstitial pneumonia: it's the epithelium, stupid!
PMID- 23155211
TI - CD14(+)S100A9(+) myeloid-derived suppressor cells portend decreased survival in
patients with advanced lung cancer.
PMID- 23155212
TI - Maternal smoking during pregnancy and its effect on childhood asthma:
understanding the puzzle.
PMID- 23155213
TI - Evaluating the NET influence of inflammation on pneumonia biology.
PMID- 23155214
TI - Personalized medicine: the road ahead.
PMID- 23155215
TI - Tracheobronchial involvement in chronic eosinophilic pneumonia.
PMID- 23155216
TI - CD64, a reliable biomarker of bacterial infection in intensive care units?
PMID- 23155217
TI - Neutrophil CD64 expression is elevated in acetaminophen-induced acute liver
failure.
PMID- 23155218
TI - Pulmonary function abnormalities in children with active Crohn's disease.
PMID- 23155219
TI - Takotsubo syndrome secondary to adrenal adenocarcinoma: cortisol as a possible
culprit.
PMID- 23155220
TI - Chronic pulmonary aspergillosis due to Aspergillus niger.
PMID- 23155221
TI - Heart failure risk among patients with rheumatoid arthritis starting a TNF
antagonist.
AB - BACKGROUND: While heart failure (HF) is associated with elevations in tumor
necrosis factor (TNF)alpha, several trials of TNF antagonists showed no benefit
and possibly worsening of disease in those with known severe HF. We studied the
risk of new or recurrent HF among a group of patients receiving these agents to
treat rheumatoid arthritis (RA). METHODS: We used data from four different US
healthcare programmes. Subjects with RA receiving methotrexate were eligible to
enter the study cohort if they added or switched to a TNF antagonist or another
non-biological disease modifying antirheumatic drug (nbDMARD). These groups were
compared in Cox regression models stratified by propensity score decile and
adjusted for oral glucocorticoid dosage, prior HF hospitalisations, and the use
of loop diuretics. RESULTS: We compared 8656 new users of a nbDMARD with 11 587
new users of a TNF antagonist with similar baseline covariates. The HR for the
TNF antagonists compared with nbDMARD was 0.85 (95% CI 0.63 to 1.14). The HR was
also not elevated in subjects with a history of HF. But, it was elevated prior to
2002 (HR 2.17, 95% CI 0.45 to 10.50, test for interaction p=0.036). Oral
glucocorticoids were associated with a dose-related gradient of HF risk: compared
with no use, 1<=5 mg HR 1.30 (95% CI 0.91 to 1.85), >=5 mg HR 1.54 (95% CI 1.09
to 2.19). CONCLUSIONS: TNF antagonists were not associated with a risk of HF
hospital admissions compared with nbDMARDs in this RA population.
PMID- 23155222
TI - Individualised aerobic and resistance exercise training improves
cardiorespiratory fitness and reduces cardiovascular risk in patients with
rheumatoid arthritis.
AB - BACKGROUND AND OBJECTIVES: Low cardiorespiratory fitness (CRF) is a significant
predictor of cardiovascular disease (CVD), and interventions aiming at increasing
CRF are known to reduce CVD risk. The effects of such interventions on CVD risk
have not been studied in patients with rheumatoid arthritis (RA). METHODS: 40
age, gender, body mass index (BMI) and disease duration matched RA patients were
allocated to either an exercise (receiving 6 months individualised aerobic and
resistance high intensity exercise intervention, three times per week), or
control (receiving advice on exercise benefits and lifestyle changes) arm.
Participants were assessed at baseline, 3 and 6 months for aerobic capacity
(VO2max), individual CVD risk factors (blood pressure, lipids, insulin
resistance, body composition), 10-year CVD event probability and RA
characteristics (C-reactive protein (CRP), Disease Activity Score 28 (DAS28) and
Health Assessment Questionnaire (HAQ)). RESULTS: There were no differences
between groups at baseline in any of the assessed variables. VO2max (p=0.001),
blood pressure (systolic: p<0.001; diastolic: p=0.003), triglycerides (p=0.030),
high density lipoprotein (HDL; p=0.042), total cholesterol:HDL ratio (p=0.005),
BMI (p=0.001), body fat (p=0.026), 10-year CVD event probability (p=0.012), CRP
(p=0.042), DAS28 (p=0.008) and HAQ (p=0.003) were all significantly improved in
the exercise versus the control group. The change in VO2max was the strongest
predictor for the observed improvements in all of the assessed CVD risk factors
and disease characteristics. CONCLUSIONS: Individualised aerobic and resistance
exercise intervention can lead to significantly improved CRF, individual CVD risk
factors, composite CVD risk, and disease activity and severity in RA patients.
PMID- 23155223
TI - Meta-analysis suggests that intensive non-biological combination therapy with
step-down prednisolone (COBRA strategy) may also 'disconnect' disease activity
and damage in rheumatoid arthritis.
AB - BACKGROUND/OBJECTIVE: Treatment of rheumatoid arthritis (RA) with tumour necrosis
factor (TNF) antagonists changes the relationship between disease activity and
progression of radiological joint damage ('disconnect'): patients who have little
or no response of disease activity still show reductions in damage progression.
In early RA, the COBRA strategy (combination of methotrexate and sulfasalazine
with step-down prednisolone) has been shown to be equivalent to high-dose
methotrexate and infliximab in suppressing damage progression (BeSt trial). We
investigated whether COBRA treatment can also 'disconnect' disease activity and
damage. DESIGN: A meta-analysis combined data from the COBRA trial (COBRA vs
sulfasalazine monotherapy) with that of two arms of the BeSt trial (COBRA vs
sequential monotherapy). Linear regression related 1-year progression of damage
(Sharp van der Heijde score) as a dependent variable with disease activity (time
averaged Disease Activity Score in 44 joints (DAS44) or C-reactive protein
(CRP)), treatment strategy (COBRA or control) and their interaction (indicator of
a disconnect) as independent variables. The main outcome was the pooled
interaction term. RESULTS: Complete data from 60-100% of patients were available.
Before pooling, disease activity was the only (strongly) significant independent
factor related to damage progression. The pooled interaction term was (weakly)
significant: time-averaged DAS44*treatment interaction, one-sided p=0.027; time
averaged CRP*treatment interaction, one-sided p=0.044. CONCLUSIONS: Changes in
the relationship between disease activity and damage progression may not be
limited to anti-TNF treatment, but a property of early, rapid and deep
suppression of joint inflammation, also induced by conventional strategies that
include glucocorticoids.
PMID- 23155224
TI - Pre- and postoperative treatment modalities for esophageal squamous cell
carcinoma.
AB - BACKGROUND: The objective of this article was to review randomized clinical
trials (RCTs) utilizing pre- and postoperative treatment modalities for
esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: A computerized
(MEDLINE) and manual search was performed to identify articles published on this
topic between 1984 and 2012. RESULTS: We identified a total of 49 published RCTs,
which included a total of 8,785 patients with ESCC. Treatment modalities
consisted of pre- (n=38) and postoperative (n=11) chemo-, radio- and
chemoradiotherapy. While both preoperative chemotherapy and chemoradiotherapy
apparently improve R0 resection, they often result in substantial postoperative
morbidity and mortality. Only for preoperative chemoradiotherapy does there seem
to be a significant benefit in overall survival. CONCLUSION: R0 resection remains
the only curative therapy for patients with ESCC. While preoperative
chemoradiotherapy may improve overall survival, there is still the need for well
designed RCTs, which should include a homogeneous patient collective, to clarify
the question of definitive benefit.
PMID- 23155225
TI - Utility of hypertension as a surrogate marker for efficacy of antiangiogenic
therapy in NSCLC.
AB - A plateau has been reached in the efficacy of cytotoxic chemotherapy for non
small cell lung cancer (NSCLC), highlighting the need for novel treatments for
this poor-prognosis malignancy. Antiangiogenic agents, including the approved
vascular endothelial growth factor (VEGF)-targeted monoclonal antibody,
bevacizumab, as well as a number of investigational tyrosine kinase inhibitors
(TKIs) that simultaneously target multiple angiogenic pathways, have demonstrated
activity in patients with NSCLC. However, unlike the epidermal growth factor
receptor (EGFR) TKIs erlotinib and gefitinib, for which the presence of EGFR
activating mutations are now known to predict response, no validated markers
currently exist for the efficacy of antiangiogenic agents. Hypertension has been
associated with antiangiogenic therapy and has also been evaluated as a surrogate
marker for efficacy with this class of agents, although analyses, to date, have
yielded conflicting results. This review provides a summary of currently
available, clinically relevant data on the incidence of hypertension with VEGF
targeted antibodies and multitargeted antiangiogenic TKIs in advanced NSCLC and
discusses the potential predictive role of hypertension on antiangiogenic therapy
in such patients.
PMID- 23155226
TI - Biomarkers of pituitary neoplasms.
AB - In a wide spectrum of tumors, cell proliferation, vascularity, apoptosis, cell
adhesion, and cell-cycle progression may indicate tumor progression. In this
review article, the literature regarding apoptotic markers and p53, as well as
cyclooxygenase-2, galectin-3, and pituitary tumor-transforming factor,
proliferative markers, angiogenesis, including vascular endothelial growth factor
and its receptor, pituitary tumor-transforming gene, microarrays, stem cells, and
microenvironment and tumor heterogeneity are presented. Only a particular group
of selected biomarkers show promise in differentiating pituitary tumors which
will behave in an aggressive manner. Therefore, the most common and promising
biomarkers and terms were analyzed, proposing the need for uniform design and
application of methods and standardized criteria for the interpretation of
results. The new spectrum of biomarkers may shed light upon the pathogenetic
mechanisms and also may serve as standardized diagnostic tool for daily
pathologic practice.
PMID- 23155227
TI - Recent trends in epidemiology of brain metastases: an overview.
AB - Brain metastases (BM) are the most common intracranial neoplasm in adults.
Initially considered as an essentially terminal stage of advanced cancer, BM are
increasingly being recognized as an emerging area of clinical interest. Their
epidemiological characteristics have changed significantly, including an
increased incidence in tumors frequently associated with BM, such as lung and
breast cancer or melanoma, but also a more frequent occurrence with other primary
tumor entities such as renal, colorectal and ovarian cancer. BM are more commonly
diagnosed in multiple intracerebral sites, but in the context of controlled
extracranial disease. Accordingly, progress in the development of systemic
treatments, together with the rationalized use of surgical resection,
radiosurgery and whole-brain radiotherapy, have led to an increase in the number
of long-term survivors and in median survival. The recent emergence of targeted
therapies and growing knowledge regarding the specific biology of BM should allow
further improvements in prognosis of this devastating disease.
PMID- 23155228
TI - Gene expression and protein array studies of folliculin-regulated pathways.
AB - The familial cancer syndrome Birt-Hogg-Dube syndrome is characterised by the
development of skin (fibrofolliculomas) and renal tumours (and lung cysts) and is
caused by mutations in the FLCN tumour suppressor gene. Though the FLCN gene
product (folliculin) has been linked to the regulation of a variety of signalling
pathways (e.g. the mTOR, AMPK, TGFbeta and hyoxia-responsive genes) the precise
function of the folliculin protein is not well-defined. In order to identify
potential novel pathways linked to folliculin function we analysed paired
isogenic folliculin-deficient and folliculin-expressing cell lines by gene
expression and protein (Kinexus) arrays. Gene expression microarray analysis in
the folliculin +/- non-renal cancer line (FTC133), revealed 708 differentially
expressed targets (fold change >2 and p<0.001) with enrichment of genes in the
cadherin and Wnt signalling pathways. Comparison of the differentially expressed
genes in the FTC133 datasets and previously reported gene expression data for a
folliculin-deficient renal tumour and the UOK257 renal cell carcinoma cell line,
revealed that RAB27B was dysregulated in all three datasets (increased expression
in folliculin-deficient cells). The Kinexus protein array analysis suggested 73
candidate, differentially expressed, proteins and further investigation by
western blot analysis of 5 candidates that were also differentially expressed in
the FTC133 gene expression microarray data, revealed that EIF2AK2 (PKR) and CASP1
were reduced and PLCG2 was increased in folliculin-deficient FTC133 cells and in
a BHD renal tumour. In view of the role of CASP1 in apoptosis we investigated
whether other apoptosis-related proteins might be regulated by folliculin and
found increased levels of SMAC/Diablo and HtrA2 in folliculin-expressing FTC133
cells. These findings identify novel pathways and targets linked to folliculin
tumour suppressor activity.
PMID- 23155229
TI - Antitumor effects of synthetic 6,7-annulated-4-substituted indole compounds in
L1210 leukemic cells in vitro.
AB - BACKGROUND: Because annulated indoles have almost no representation in the
PubChem or MLSMR databases, an unprecedented class of an indole-based library was
constructed, using the indole aryne methodology, and screened for antitumor
activity. Sixty-six novel 6,7-annulated-4-substituted indole compounds were
synthesized, using a strategic combination of 6,7-indolyne cycloaddition and
cross-coupling reactions under both Suzuki-Miyaura and Buchwald-Hartwig
conditions, and tested for their effectiveness against murine L1210 tumor cell
proliferation in vitro. MATERIALS AND METHODS: Various markers of tumor cell
metabolism, DNA degradation, mitotic disruption, cytokinesis and apoptosis were
assayed in vitro to evaluate drug cytotoxicity. RESULTS: Most compounds inhibited
the metabolic activity of leukemic cells in a time- and concentration-dependent
manner but only 9 of them were sufficiently potent to inhibit L1210 tumor cell
proliferation by 50% in the low-MUM range after 2 (IC(50): 4.5-20.4 MUM) and 4
days (0.5-4.0 MUM) in culture. However, the antiproliferative compounds that were
the most effective at day 4 were not necessarily the most potent at day 2,
suggesting different speeds of action. A 3-h treatment with antiproliferative
annulated indole was sufficient to inhibit, in a concentration-dependent manner,
the rate of DNA synthesis measured in L1210 cells over a 0.5-h period of pulse
labeling with (3)H-thymidine. Four of the antiproliferative compounds had weak
DNA-binding activities but one compound reduced the fluorescence of the ethidium
bromide-DNA complex by up to 53%, suggesting that some annulated indoles might
directly interact with double-stranded DNA to disrupt its integrity and prevent
the dye from intercalating into DNA base pairs. However, all 9 antiproliferative
compounds induced DNA cleavage at 24 h in L1210 cells, containing (3)H-thymidine
prelabeled DNA, suggesting that these antitumor annulated indoles might trigger
an apoptotic pathway of DNA fragmentation. Indeed the antiproliferative annulated
indoles caused a time-dependent increase of caspase-3 activity with a peak at 6
h. Interestingly, the compounds with the most potent antiproliferative IC(50)
values at day 2 were consistently the most effective at inhibiting DNA synthesis
at 3 h and inducing DNA fragmentation at 24 h. After 24-48 h, antiproliferative
concentrations of annulated indoles increased the mitotic index of L1210 cells
and stimulated the formation of many bi-nucleated cells, multi-nucleated cells,
apoptotic cells and micronuclei, suggesting that these antitumor compounds might
enhance mitotic abnormality, induce chromosomal damage or missegregation, and
block cytokinesis to induce apoptosis. CONCLUSION: Although annulated indoles may
have interesting bioactivity, novel derivatives with different substitutions must
be synthesized to elucidate structure-activity relationships, identify more
potent antitumor lead compounds, and investigate their molecular targets and
mechanisms of action.
PMID- 23155230
TI - The utility of tumor-specifically internalizing peptides for targeted siRNA
delivery into human solid tumors.
AB - BACKGROUND: Ribonucleotide reductase composed of the hRRM1 and hRRM2 subunits
catalyzes the conversion of ribonucleotides to their corresponding deoxy forms
for DNA replication. Anti-hRRM2 siRNA degrades hRRM2's mRNA and suppresses
tumorigenesis. A Phase I clinical trial demonstrated its therapy potential. HN-1
represents a tumor-specifically internalizing peptide for targeted-drug delivery
into human head and neck squamous cell carcinoma. MATERIALS AND METHODS:
Internalization of peptide was monitored by fluorescence microscopy. The peptide
siRNA conjugate was chemically synthesized. The hRRM2 expression was monitored by
western blot analysis. RESULTS: HN-1(TYR) (HN-1 with two N-terminally added
tyrosines) was internalized by human head and neck or breast cancer cells. Anti
hRRM2 siRNA(R) (resistant to RNase degradation) was conjugated to HN-1(TYR)
without compromising their properties. The treatment with HN-1(TYR)-anti-hRRM2
siRNA(R) partly suppressed the endogenously expressed hRRM2 in human breast
cancer cells. CONCLUSION: Our results establish the utility of tumor-specifically
internalizing peptides for targeted siRNA delivery into human cancer cells.
PMID- 23155231
TI - Protein kinase C regulates bombesin-induced rapid VEGF secretion in neuroblastoma
cells.
AB - BACKGROUND: Intracellular signaling responsible for gastrin-releasing peptide
(GRP) receptor-mediated neovascularization is not clearly understood. We sought
to determine the cellular mechanisms involved in the GRP receptor regulation of
vascular endothelial growth factor (VEGF) release in neuroblastoma cells.
MATERIALS AND METHODS: BE(2)-C cells were treated with bombesin (BBS), the
amphibian equivalent of GRP, Phorbol myristate acetate (PMA) a PKC agonist, or
GF109293X (GFX), and analyses were performed for VEGF secretion, phosphorylated
protein kinase B (AKT), extracellular signal-regulated kinases (ERK) and protein
kinase D (PKD) expression. RESULTS: BBS rapidly increased VEGF secretion at 30
min. Pre-treatment with PMA alone produced similar results; this effect was
synergistic with the addition of GRP. Conversely, GFX blocked PMA-stimulated
increase in VEGF secretion. Immunofluorescent staining for VEGF correlated to
BBS, PMA and GFX. CONCLUSION: PKC is critically responsible for rapid VEGF
secretion by GRP receptor signaling in neuroblastoma cells. Inhibition of VEGF
significantly reduced GRP-mediated cell proliferation, suggesting its crucial
role in neuroblastoma tumorigenesis.
PMID- 23155232
TI - Antagonistic effect of small-molecule inhibitors of Wnt/beta-catenin in multiple
myeloma.
AB - BACKGROUND: Development and progression of multiple myeloma is dependent on the
bone marrow (BM) microenvironment, and within the BM, a number of factors are
secreted, including the Wnt ligands. Bone marrow stromal cells (BMSC) secrete Wnt
ligands that activate Wnt signaling in multiple myeloma. The canonical Wnt
pathway which is mediated through the transcriptional effector beta-catenin (beta
cat) is commonly de-regulated in many cancers. Cells with active beta-cat
regulated transcription (CRT) are protected against apoptosis; conversely,
inhibition of CRT may prevent cell proliferation. MATERIALS AND METHODS: In this
study, we tested the efficacy of recently described inhibitors of CRT (iCRTs;
oxazole and thiazole) for their selective antagonistic effect on Wnt-beta-cat
response in MM cells MM.1, U266, BMSC and primary BMMC obtained from patient
samples (n=16). RESULTS: We demonstrated that iCRTs we used, block Wnt/beta-cat
reporter activity, down regulate beta-cat expression and inhibit cell
proliferation in a dose-dependent manner with an optimal dose closer to 15 MUM.
Our data further indicate that iCRTs do not influence the expression of the
upstream components of the Wnt pathway DKK1 at the optimal dose, suggesting that
iCRTs may specifically target beta-cat in MM cells. Additionally, iCRT-treatment
of MM cells, co-cultured with BMSC, showed an inhibitory effect on VEGF and cell
migration. CONCLUSION: This study provides the first in vitro data evaluation of
newly-described iCRTs as potential Wnt-beta-cat/VEGF pathway antagonists in
multiple myeloma.
PMID- 23155233
TI - Analysis of p53 and miRNA expression after irradiation of glioblastoma cell
lines.
AB - Glioblastoma is a malignant brain tumor that is difficult to completely cure by
surgical treatment alone. However, resistance to anticancer drugs and radiation
may be acquired during treatment. For instance, miRNAs involved in regulating the
expression of genes inducing apoptosis and other specific genes have been
proposed for use, in order to induce the apoptosis of radioresistant cancer
cells. A172 glioblastoma cells, expressing wild-type p53 were irradiated to a
total dose of up to 60 Gy allowing us to analyze the activities of apoptosis
related proteins. The miR-34a expression levels in cells after irradiation at 30
and 60 Gy were 0.17- and 18.7-times the BCL2 and caspase-9 expression levels,
respectively. The high miR-34a expression level in the cells after irradiation at
60 Gy reduced the p53 expression level. This study suggests that apoptosis might
be promoted by regulating the action of miRNAs, even in cells that have acquired
radioresistance.
PMID- 23155234
TI - DNA methylation in ATRA-treated leukemia cell lines lacking a PML-RAR chromosome
translocation.
AB - A deficient retinoic acid signaling has been suggested to be an important cause
of the clinical inefficacy of all-trans retinoic acid (ATRA) therapy in non
promyelocytic (non-PML) forms of acute myeloid leukemia (AML). The general aim of
the present work was to explore novel ways to take advantage of the anti-leukemic
potential of ATRA, and, specifically, to search for a synergism between ATRA and
epigenetic drugs. Because previous reports have found no major influence of ATRA
on DNA methylation, we investigated whether ATRA-mediated differentiation of the
U937 and HL-60 AML cell lines, both lacking a PML-retinoic acid receptor (RAR)
fusion product, is accompanied by early-appearing and weak changes in CpG
methylation. We report that in HL-60 cells, by using a highly quantitative
analysis of a set of genes found to be abnormally expressed in AML, polymerase
chain reaction (PCR)-amplified p16 gene promoter molecules (each with 15 CpG
sites), exhibited a CpG methylation level of 0-4% in untreated cells, which
increased to 4-21% after treatment with ATRA for seven days. In contrast to HL-60
cells, U937 cells exhibited a very high CpG methylation level in p16, and ATRA
did not influence the promoter methylation of this gene. In the total CCGG sites
of the genome, analysed using a methylation-sensitive restriction enzyme, CpG
methylation was significantly lower in ATRA-treated HL-60 (p<0.01) and U937 cells
(p<0.05) than in controls. Taken together, our findings show that ATRA can
influence DNA methylation, and suggest that future research should investigate
whether epigenetic modulation may evoke a clinical effect of ATRA in leukemia.
PMID- 23155235
TI - Initial activation status of the antioxidant response determines sensitivity to
carboplatin/paclitaxel treatment of ovarian cancer.
AB - BACKGROUND/AIM: Ovarian carcinoma is the main cause of gynecological cancer
related deaths. The aim of this study was to determine the activation status of
the antioxidant response in samples of ovarian serous carcinoma from paraffin
embedded biopsies and compare them with the response of patients to carboplatin
paclitaxel treatment. MATERIALS AND METHODS: Estrogen receptor alpha (ERalpha),
antioxidant enzymes, and uncoupling protein (UCP) levels were analyzed by western
blotting and the presence of estrogen receptor beta (ERbeta) was investigated by
immunohistochemistry (IHC). RESULTS: Lower levels of ERalpha, antioxidant enzymes
and UCPs were found in patients resistant to treatment in comparison to the
carboplatin/paclitaxel-sensitive ones; IHC revealed a greater presence of ERbeta
in sensitive patients. CONCLUSION: These results indicate that patients resistant
to treatment have a lower level of antioxidant response activation compared to
sensitive patients, fact which may be related to the efficacy of this treatment.
PMID- 23155236
TI - In NSCLC, VEGF-A response to hypoxia may differ between squamous cell and
adenocarcinoma histology.
AB - AIM: To investigate if hypoxia induces vascular endothelial growth factor (VEGF)
A and VEGF-C secretion in non-small cell lung cancer (NSCLC) cells and if the
secretion is cell type-dependent. MATERIALS AND METHODS: Adenocarcinoma (AC)
(H522, PAC) and squamous cell carcinoma (SCC) (H520) cell lines were exposed to
hypoxia and normoxia. Supernatants were analysed with enzyme-linked immunosorbent
assay (ELISA). Tissue microarrays, from 304 patients diagnosed with stage I-IIIA
NSCLC, were immunohistochemically-stained and scored for VEGF-A and VEGF-C.
RESULTS: In vitro, VEGF-A expression in hypoxic AC cells was significantly higher
than that in normoxic cells (H522: p=0.004, PAC; p=0.007). In contrast, hypoxia
led to significantly reduced VEGF-A production in the SCC cell line compared to
normoxic cells (p=0.005). CONCLUSION: In vitro, AC and SCC exhibit different VEGF
A responses to hypoxia. Hypoxia mediates a pro-angiogenic response in AC, but
apparently not in SCC.
PMID- 23155237
TI - Cytotoxicity and type of cell death induced by midazolam in human oral normal and
tumor cells.
AB - BACKGROUND: Intravenous anesthetics have been used during the treatment of
various malignant tumors, however, their effects on oral tissues is not well
understood. In the present study, the cytotoxicity of five intravenous
anesthetics towards oral tumor and normal cells was compared. MATERIALS AND
METHODS: Tumor specificity index was determined by the ratio of the mean 50%
cytotoxic concentration for normal cells to that for tumor cells. Apoptosis
induction was monitored by internucleosomal DNA fragmentation and caspase-3, -8,
and -9 activation. Fine cell structure was observed under transmission electron
microscopy. RESULTS: Benzodiazepines (midazolam and diazepam) exhibited higher
cytotoxicity than barbiturates (thiopental and thiamylal), whereas propofol had
the intermediate range of cytotoxicity. Midazolam showed the highest
cytotoxicity. HL-60 cells were the most sensitive to midazolam, followed by
epidermal keratinocytes, oral squamous cell carcinoma (OSCC), glioblastoma and
then oral normal cells. Midazolam did not induce the production of apoptosis
markers such as internucleosomal DNA fragmentation and activation of caspase-3,
8 and -9, but did induce the appearance of many vacuoles, mitochondrial swelling
and cell membrane rupture in OSCC cell lines (HSC-2 and HSC-4) cells. The
cytotoxicity of midazolam was not reduced by pre-treatment with autophagy
inhibitors (3-methyladenine and bafilomycin A1). CONCLUSION: These results
suggest that midazolam may induce necrotic cell death, rather than apoptosis or
autophagy, in OSCC cell lines.
PMID- 23155238
TI - Chemokine receptors and chemokine production by CD34+ stem cell-derived monocytes
in response to cancer cells.
AB - BACKGROUND: The chemokine-chemokine receptor (CR) network is involved in the
regulation of cellular infiltration of tumours. Cancer cells and infiltrating
macrophages produce a whole range of chemokines. This study explored the
expression of some CR and chemokine production by cord blood stem cell-derived
CD34(+) monocytes and their novel CD14(++)CD16(+) and CD14(+)CD16(-) subsets in
response to tumour cells. MATERIAL AND METHODS: CR expression was determined by
flow cytometry and their functional activity by migration to chemoattractants.
Monocytes were cultured with tumour cells and the chemokine content was assessed
in culture supernatants. RESULTS: CD14(++)CD16(+) monocytes exhibited increased
expression of chemokine (C-C) receptor (CCR) 1, while CD14(+)CD16(-) of CCR2,
chemokine (C-X-C) receptor (CXCR) 1, 2 and 4. The increased expression of CCR2 on
CD14(+)CD16(-) monocytes was associated with their enhanced migration to monocyte
chemoattractant protein-1 (CCL2), MCP-3 (CCL7), MCP-2 (CCL8) and MCP-4 (CCL13),
while that of CXCR1 and 2 to interleukin 8 (CXCL8), and CXCR4 to stromal cell
derived factor-1 (CXCL12). Tumour cells induced production of macrophage
inflammatory protein-1alpha (CCL3) MIP-1beta and regulated on activation normal T
cells expressed and secreted (CCL5) but not CCL2 or CXCL8, monokine induced by
gamma interferon (CXCL9), interferon gamma-induced protein 10 (CXCL10).
CONCLUSION: The studied monocyte subsets, in comparison to those from blood,
exhibit different expression of CRs and response to the stimuli that occur from
tumour cells.
PMID- 23155239
TI - An immobilized antibody targeting N-cadherin facilitates spread of N-cadherin
positive tumour cells.
AB - BACKGROUND: We investigated whether an antibody targeting N-cadherin facilitates
the adhesion and spreading of N-cadherin-positive tumour cells under static
conditions. MATERIALS AND METHODS: Two human melanoma cell lines, HMB-2 and BLM,
were selected for their presence and lack of expression of N-cadherin,
respectively. In vitro adhesion experiments were performed in the presence of a
monoclonal antibody targeting N-cadherin (GC-4) or a control (antibody to alpha
tubulin). Quantitative data from the spreading assays were calculated by
converting the images obtained by fluorescence microscopy to binary images.
RESULTS: For HMB-2 cells, the average cell width was significantly larger in the
presence of GC-4 vs. control at all measured time points, with the exception of
the measurement at 70 minutes (p=0.051). No differences were observed between
controls and GC-4 for BLM cells. CONCLUSION: The adhesion and spread of N
cadherin-positive tumour cells can be facilitated by the presence of an
immobilized antibody to N-cadherin.
PMID- 23155240
TI - Cisplatin enhances interaction between p66Shc and HSP27: its role in
reorganization of the actin cytoskeleton in renal proximal tubule cells.
AB - BACKGROUND/AIM: Cisplatin nephrotoxicity includes early activation of the pro
apoptotic p66Shc and disorganization of the actin cytoskeleton, integrity which
is regulated by heat-shock protein-27 (Hsp27). Here we determined the potential
role of p66Shc in abrogating the Hsp27 function. MATERIALS AND METHODS: Effects
of p66Shc knockdown and Hsp27 overexpression on F-actin stress fibers after
cisplatin treatment were visualized by phalloidin staining. Binding of p66Shc to
Hsp27 after cisplatin treatment was determined by immunoprecipitation in cell and
tissue lysates. The role of p66Shc and its Ser36 phosphorylation in Hsp27 binding
was assessed by overexpressing it or mutating its Ser36 residue. RESULTS:
Knockdown of p66Shc and overexpression of Hsp27 ameliorated cisplatin-mediated
collapse of the actin cytoskeleton. Further studies revealed that p66Shc binds
Hsp27 after treatment with cisplatin that requires Ser36 phosphorylation of
p66Shc. CONCLUSION: We propose a novel function of p66Shc that, through
interacting with Hsp27, accelerates cisplatin-dependent disruption of the actin
cytoskeleton.
PMID- 23155241
TI - MTNR1A receptor expression in normal and pathological human salivary glands.
AB - AIM: To analyze and compare the expression of MTNR1A receptor in normal and
pathological major and minor salivary glands. MATERIALS AND METHODS: Twenty
samples of major and minor salivary glands and 10 with Warthin's tumor were
studied. Expression of the MTNR1A receptor (goat polyclonal antibody raised
against a peptide mapping at the N-terminus of MEL-1A R of human origin) was
analyzed. RESULTS: The excretory ducts of major salivary glands demonstrated
intense intracytoplasmic positivity but scant cytoplasmic membrane positivity for
MTNR1A. The studied Warthin's tumors showed intense cytoplasmic positivity for
MT1 receptor in all cylindrical epithelial cells lining spaces and a less intense
positivity in basal cells. The lymphoid component accompanying the tumor was
negative for MT1 receptor. CONCLUSION: Intense intracytoplasmic positivity for
the MTNR1A receptor in the excretory ducts of human major and minor salivary
glands and Warthin's tumor was found. The intense expression of MTNR1A receptors
observed in this study in the excretory ducts of major and minor salivary glands
may be related to salivary regulation.
PMID- 23155242
TI - Non-invasive X-ray micro-computed tomographic evaluation of indomethacin on
urethane-induced lung carcinogenesis in mice.
AB - BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide.
We previously reported that respiration-gated X-ray micro-computed tomography
(micro-CT) is a useful tool for analyzing lung tumor development in animal
models. MATERIALS AND METHODS: Lung tumors were induced by a single
intraperitoneal injection (250 mg/kg) of urethane in male A/J mice, followed by
indomethacin treatment at 5 ppm in the diet. The mice were scanned by micro-CT
every 4 weeks from 10 to 26 weeks after urethane administration. RESULTS: Total
incidence and multiplicity of lung tumors were not significantly reduced by
indomethacin treatment, as compared with untreated mice. However, the incidence
of adenocarcinoma tended to be reduced by indomethacin treatment. Moreover, the
size of lung tumors, especially adenomas, was suppressed by indomethacin
treatment. Micro-CT analysis revealed that indomethacin effectively suppressed
tumor development after urethane treatment for 10 weeks. CONCLUSION: These
findings indicate that indomethacin suppresses lung carcinogenesis in mice and
micro-CT is a useful non-invasive imaging approach for evaluating the
characteristics and suppression of lung tumors in mice treated with cancer
chemopreventive agents.
PMID- 23155243
TI - Phenolic diterpenes derived from Hyptis incana induce apoptosis and G(2)/M arrest
of neuroblastoma cells.
AB - BACKGROUND: Neuroblastoma is one of the most commonly encountered solid tumors in
the pediatric age group, and the prognosis of patients with advanced
neuroblastoma is very poor. In this study, the antitumor effects of five phenolic
diterpenes derived from Hyptis incana (Lamiaceae), a Brazilian medicinal plant,
were examined on neuroblastoma cells. MATERIALS AND METHODS: Cytotoxicity was
assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
(MTT) assay. Apoptotic nuclear shrinkage was monitored by Hoechst 33342 staining.
The cell-cycle status was evaluated by flow cytometry and protein alterations
were monitored by western blotting. Differentiated cells were photographed and
counted in a randomized fashion. RESULTS: All of the examined compounds exhibited
significant cytotoxicity towards the neuroblastoma cells. In particular, 7
ethoxyrosmanol had a high degree of efficacy. Nuclear condensation and
degradation of procaspase-3 and -9 were observed after treatment of the cells
with these compounds. Moreover, phenolic diterpenes induced cell-cycle arrest in
the G(2)/M phase. Rosmanol and epirosmanol tended to induce differentiation.
CONCLUSION: Phenolic diterpenes isolated from H. incana have multiple antitumor
effects on neuroblastoma cells.
PMID- 23155244
TI - Marked increase of CYP24A1 mRNA level in hepatocellular carcinoma cell lines
following vitamin D administration.
AB - AIM: 1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) inhibits cell growth and
induces apoptosis in numerous types of tumors. We aimed to examine the mRNA and
protein expression of 1,25(OH)(2)D(3)-inactivating CYP24A1 and mRNA expression of
the activating CYP27B1 enzymes, as well as that of vitamin D receptor (VDR), in
hepatocellular carcinoma (HCC) cell cultures in response to 1,25(OH)(2)D(3)
administration. MATERIALS AND METHODS: Increasing amounts of 1,25(OH)(2)D(3)
(0.256-10 nM) were added to cultures of HepG2, Huh-Neo, Hep3B, Huh5-15 human HCC
cell lines and cells then incubated for various time periods (30 min-28 h). The
mRNA expression was analyzed by real time reverse transcription-polymerase chain
reaction (RT-PCR). CYP24A1 protein in HepG2 cells was detected by
immuncytochemistry. RESULTS: CYP24A1 mRNA expression significantly (p<0.0001)
increased in response to 1,25(OH)(2)D(3) administration in two cell lines: in
HepG2 cells, the CYP24A1 mRNA level exhibited 5,300-fold elevation, reaching a
maximum value at 8 h; in Huh-Neo cells, the increase was 152-fold that of the
baseline value, with the maximum being reached at 14 h. There was no significant
change in Hep3B and Huh5-15 cell lines, nor was there any change in CYP27B1 and
VDR gene expression in any cell cultures. Immuncytochemistry in HepG2 cells
proved that gene activation was followed by CYP24A1 protein synthesis.
CONCLUSION: Our novel data indicate that administration of 1,25(OH)(2)D(3)
results in a marked increase of CYP24A1 mRNA expression in some, but not all,
human HCC lines in vitro. These differences could be dependent upon the origin of
the tumor cells.
PMID- 23155245
TI - Expression of human endogenous retrovirus-K coincides with that of micro-RNA-663
and -638 in germ-cell tumor cells.
AB - BACKGROUND/AIM: The cell line GH was established from germ-cell tumor tissue;
human endogenous retrovirus-K (HERV-K) expression was detectable after prolonged
culture of the cells, particularly in cells that formed domes and vesicles. In
addition, keeping GH cells in culture at high cell densities increased HERV-K
expression. Here, we studied whether this inducible HERV-K expression is
accompanied by differences in microRNA (miRNA) expression patterns of GH cells.
MATERIALS AND METHODS: The global miRNA expression pattern of GH cell samples
(HERV-K high versus low) was analyzed by miRNA arrays. RESULTS: Two miRNAs were
found to be differentially regulated and to exhibit expression parallel to that
of HERV-K. The identified miRNAs-663 and -638, have been reported to be involved
in multiple processes, including cellular senescence. However, induction of HERV
K expression did not change the cellular senescence status of GH cells.
CONCLUSION: The expression of these two miRNAs might be useful as novel
diagnostic and prognostic markers in patients with tumors.
PMID- 23155246
TI - Interaction of MTHFR C677T and A1298C, and MTR A2756G gene polymorphisms in
breast cancer risk in a population in Northeast Brazil.
AB - Polymorphisms in genes encoding enzymes of folate metabolism are a focus of
breast cancer risk studies due of the role of these enzymes in DNA methylation,
synthesis, and repair. MTHFR, encoding for 5,10-methylenetetrahydrofolate
reductase, is one of the most studied genes in this regard, but findings are
controversial, and the majority of studies have analyzed polymorphisms
individually. In this case control study, we examined the combination of the
polymorphisms MTHFR C677T and A1298C with MTR A2756G, where MTR, methionine
synthase, is an important enzyme of the folate cycle in the methylation pathway.
One hundred and forty-two patients with breast cancer and controls were included
and the genotypes were determined using PCR-RFLP. In the population studied,
individuals carrying the polymorphic allele in the heterozygous state for both
enzymes, MTHFR C677T and MTR A2756G, had an increased risk [odds ratio, OR=2.77
(95% confidence interval, CI=1.19-6.52)] for disease, compared to those with the
wild genotype. In addition, individuals carrying the MTR 2756 genotype AG had an
increased risk when this was combined with the MTHFR 1298 genotype CC [OR=5.13
(95% CI=0.87-38.82)]. No significant results were found from the analyses
associating the MTHFR C677T and A1298C genotypes. However, when stratifying the
patients by age (50 years old as the cut-off), patients over 50 years old had
greater risk, with the presence of both MTHFR polymorphisms in the heterozygous
state [OR=5.33 (95% CI=1.42-21.03)]. This study points out the importance of the
interactions between the MTHFR C677T, MTHFR A1298C and MTR A2756G polymorphisms,
and also highlights the relevance of the MTR A2756G polymorphism and age in
breast cancer risk.
PMID- 23155247
TI - Desensitization of NFkappaB for overcoming chemoresistance of pancreatic cancer
cells to TNF-alpha or paclitaxel.
AB - BACKGROUND: Chemotherapy-induced nuclear factor kappaB (NFkappaB) activation is
thought to play a key role in acquisition of chemoresistance by cancer cells. We
focused on blockade of this activation by using the observation so-called
'desensitization' of NFkappaB using known NFkappaB activator, doxycycline.
MATERIALS AND METHODS: The human pancreatic cancer cell line PANC-1 was incubated
with doxycycline, followed by treatment with tumor necrosis factor (TNF)-alpha or
paclitaxel. NFkappaB activity and the regulation of NFkappaB-related genes was
analyzed. RESULTS: Doxycycline induced sustained NFkappaB activation, followed by
desensitization to further NFkappaB activation by TNF-alpha -or paclitaxel, which
was accompanied by decreased expression of TNF receptor p55, p75, and epidermal
growth factor receptor. Consistent with these observations, doxycycline-pre
treatment resulted in an augmentation of TNF-alpha- and paclitaxel-mediated
cytotoxicity and apoptosis. CONCLUSION: These data indicate the possible clinical
application of desensitization of NFkappaB to overcome chemoresistance by
conventional chemotherapy for pancreatic cancer.
PMID- 23155248
TI - Analysis of type of cell death induced by topoisomerase inhibitor SN-38 in human
oral squamous cell carcinoma cell lines.
AB - Despite frequent use of topoisomerase inhibitors (TIs) as antitumor agents, their
application to oral squamous cell carcinoma (OSCC) has not been reported. We
investigated three inhibitors of topoisomerase I [camptothecin, irinotecan, SN-38
(active metabolite of irinotecan)] and two inhibitors of topoisomerase II
(etoposide, teniposide) for their cytotoxicity towards a total of 15 human tumor
cell lines and normal cultured cells. All TIs exhibited higher cytotoxicity
towards tumor cell lines (OSCC, glioblastoma, myelogenous leukemia) as compared
with normal mesenchymal (gingival fibroblast, pulp cell, periodontal ligament
fibroblast) and epithelial cells (skin keratinocytes). Among TIs, SN-38 had the
highest cytotoxicity towards OSCC cell lines, with a tumor specificity index of
1321 compared to mesenchymal cells and 22 compared with epithelial cells. SN-38
induced different types of cell death in two OSCC cell lines: apoptosis (caspase
3 activation and internucleosomal DNA fragmentation) in HSC-2 cells and autophagy
(formation of autophagosome and secondary lysosome) in HSC-4 cells. The cell
death of HSC-2 and HSC-4 cells was significantly inhibited by pre-treatment with
caspase inhibitor (Z-VAD-FMK) and autophagy inhibitors (3-methyladenine,
bafilomycin A1), respectively. The present study demonstrated that SN-38 is
highly cytotoxic to OSCC cell lines, regardless of the type of induced cell
death, suggesting its future application for chemotherapy of OSCC.
PMID- 23155249
TI - Suppression of cell invasion and migration by propofol are involved in down
regulating matrix metalloproteinase-2 and p38 MAPK signaling in A549 human lung
adenocarcinoma epithelial cells.
AB - Metastasis is a major cause of death of patients with malignant tumors. Matrix
metalloproteinases (MMPs) are important for the migration and invasion of various
types of cancer cell. Propofol is a known anesthetic agent, widely used for short
term anesthesia and for longer-term sedation. Propofol inhibits the proliferation
of a variety of tumor cells, but there is no available information regarding
propofol-inhibited migration and invasion of tumor cells in vitro. In this study,
we investigated the effects of propofol on the migration and invasion of human
lung carcinoma A549 cells. Wound healing assay and Boyden chamber assays
indicated that propofol inhibited the migration and invasion of A549 cells in
vitro. Gelatin zymographic analysis showed the inhibitory effect of propofol on
the activation of expression MMP-2. Western blot analysis also indicated that
propofol suppressed the protein expiration of growth factor receptor-bound
protein 2 (GRB2), Jun N-terminal kinases 1/2 (p-JNK1/2), p-p38, MMP-2 and MMP-9
in A549 cells. Results from real-time PCR assay also showed that propofol
inhibited the mRNA gene expression of MMP-2, -7 and -9, and enhanced that of
tissue inhibitor of metalloproteinase 1 (TIMP1) and TIMP2 in A549 cells. Taken
together, these data show that propofol inhibits MMP-2 and -9 mRNA and protein
expressions, resulting in suppression of lung cancer cell invasion and migration
in vitro.
PMID- 23155250
TI - Studies on combination of platinum drugs cisplatin and oxaliplatin with
phytochemicals anethole and curcumin in ovarian tumour models.
AB - Chemopreventative phytochemicals having antitumour and antioxidant properties can
overcome problems of chemoresistance and nonspecific toxicity towards normal
cells that are associated with platinum-based chemotherapy against cancer. These
agents exert their effects by bringing into play numerous cellular proteins that
in turn affect multiple steps in pathways leading to tumourigenesis. In this
study, combinations of two cytotoxic phytochemicals anethole and curcumin were
applied in binary combination with platinum drugs cisplatin and oxaliplatin to
three epithelial ovarian cancer cell lines: A2780 (parent), A2780(cisR)
(cisplatin-resistant) and A2780(ZD0473R) (ZD0473-resistant). Cell viability was
quantified using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium
bromide (MTT) reduction assay and the combined drug action was analyzed based on
the equations derived by Chou and Talalay (1984). Greatest synergism was observed
when the phytochemical was added first followed by the platinum drug 2 h later
and additiveness to antagonism in combined drug action was observed when the two
compounds were administered as a bolus. If confirmed in vivo, the appropriate
sequenced combinations of platinum with the phytochemicals may provide a means of
overcoming drug resistance.
PMID- 23155251
TI - Epigallocatechin gallate acts synergistically in combination with cisplatin and
designed trans-palladiums in ovarian cancer cells.
AB - In this study, synergism in activity from the sequenced combinations of three
trans-palladiums (denoted as TH5, TH6 and TH7) with green tea polyphenol (-)
epigallocatechin-3-gallate (EGCG), as well as that with cisplatin, was
investigated in a number of human ovarian tumour models as a function of sequence
of administration. Cellular accumulation of platinum and palladium, and the
levels of platinum-DNA and palladium-DNA binding were also determined for the 0/4
h and 0/0 h sequences of administration. The results of the study show that co
administration of cisplatin with EGCG (0/0 h) produces weak synergism in both
cisplatin-sensitive (A2780) and cisplatin-resistant (A2780(cisR)) cell lines
whereas (0/4 h) administration produces pronounced synergism in both. In
contrast, bolus administration of EGCG with TH5, TH6 and TH7 produces marked
antagonism except that with TH5, in the A2780(cisR) cell line, where a mild
synergism is observed. In the case of TH5, TH6 and TH7, administration of drugs
with a time gap (0/4 h or 4/0 h combinations) produces sequence-dependent
synergism in both A2780 and A2780(cisR) cell lines, whereas in the case of
cisplatin, marked antagonism is observed with the 4/0 h sequence of
administration in the A2780 cell line. Whereas the highly synergistic 0/4 h
sequence of combination of cisplatin with EGCG is found to be associated with
pronounced cellular accumulation of platinum and a high level of platinum-DNA
binding, no such clear trend can be seen for any of the combinations of TH5, TH6
and TH7 with EGCG. The results of the present study provide support to the idea
that sequenced combinations of platinum drugs and tumour-active palladium
compounds with selected phytochemicals such as EGCG may provide a means of
overcoming drug resistance.
PMID- 23155252
TI - Demethylation of the region around exon 2 of MLH1 gene in gastrointestinal
cancer.
AB - AIM: Our previous study showed that methylation of the mutL homolog 1 (MLH1)
promoter may spread upstream from the Alu elements in intron 1. In this study, we
investigated if the Alu methylation could also spread downstream. MATERIALS AND
METHODS: Two colorectal cancer cell lines (RKO, SW48), and four colorectal and
three gastric carcinomas [all Microsatellite Instability (MSI)-positive] were
selected as cases. Normal colorectal and gastric mucosa and human peripheral
blood, and one MSI-negative colorectal cancer case served as controls. After
extraction of DNA, bisulfite genomic sequencing was used to analyze the
methylation level of exon 2 and the adjacent part of intron 2 of the MLH1 gene.
RESULTS: Exon 2 and the partial intron 2 exhibited a high level of methylation in
controls. In contrast, demethylation in these regions was seen in
gastrointestinal cancer. CONCLUSION: Exon 2 methylation is not likely to
influence MLH1 gene expression. It seems that de-methylation of exon 2 and intron
2, in combination with intron 1, is associated with methylation spreading of the
MLH1 promoter. The region around exon 2 could possibly bind proteins that
regulate methylation, and therefore affect gene expression.
PMID- 23155253
TI - Dissimilar immunohistochemical expression of ERK and AKT between paired biopsy
and hepatectomy tissues of hepatocellular carcinoma.
AB - BACKGROUND/AIM: Biomarker studies using immunohistochemical (IHC) staining have
not been successful for advanced hepatocellular carcinoma (HCC). We aimed to
examine whether the tissue procurement process influences the protein expression
levels detected by IHC. MATERIALS AND METHODS: Forty-two tissue pairs of HCC that
had been both preoperatively biopsied and then surgically resected were included
in the study. IHC staining was used to determine expression of target molecules,
all of which were graded according to the percentage of positively stained tumor
cells. The expression of beta-catenin was analyzed according to the localization
of positive staining. RESULTS: Biopsied and surgically resected tissues exhibited
dissimilar phosphorylated extracellular signal regulated kinase (p-ERK) and
phosphorylated AKT expression levels (kappa=0.025 and 0.153, respectively). On
the contrary, p53 exhibited similar expression levels, and beta-catenin exhibited
similar staining localization patterns in biopsied and surgically resected
tissues (kappa=0.729 and 0.654, respectively). CONCLUSION: Biopsied HCC tissues
and their corresponding resected HCC tissues have inconsistent IHC-detected ERK
and AKT expressions.
PMID- 23155254
TI - MicroRNA miR-34b/c enhances cellular radiosensitivity of malignant pleural
mesothelioma cells.
AB - BACKGROUND: We previously reported that epigenetic silencing of microRNA-34b/c
(miR-34b/c) plays an important role in the pathogenesis of malignant pleural
mesothelioma (MPM). We examined the impact of miR-34b/c restoration on the
radiosensitivity of MPM cells. MATERIALS AND METHODS: We established stable miR
34b/c and scramble transfectants of two MPM cell lines, H2052 and H28. We
examined these transfectants by clonogenic survival assay, phosphorylated histone
H2AX (gammaH2AX) foci assay, cell-cycle analysis, and western blotting. RESULTS:
The clonogenic survival assay revealed that miR-34b/c radiosensitized MPM cells.
gammaH2AX foci assay showed that DNA double-strand break repair was delayed in
miR-34b/c transfectants. The proportion of sub-G(1) phase cells was increased in
miR-34b/c transfectants after irradiation. miR-34b/c inhibited expression of
cyclin-D1, cyclin-dependent kinase 4/6, B-cell lymphoma-2 (BCL-2) and increased
cleaved poly (ADP-ribose) polymerase (cPARP) and cleaved caspase-3 after
irradiation. CONCLUSION: Our results indicate that miR-34b/c enhances
radiosensitivity by promoting radiation-induced apoptosis and suggested that miR
34b/c might be a useful therapeutic molecule to enhance radiotherapy in MPM.
PMID- 23155255
TI - Interaction of radiation and gefitinib on a human lung cancer cell line with
mutant EGFR gene in vitro.
AB - AIM: To investigate the effect of gefitinib in combination with irradiation using
HCC827 cells, a human lung cancer cell line bearing epidermal growth factor
receptor (EGFR) mutation. MATERIALS AND METHODS: The effects of treatment with
radiation with and without gefitinib on HCC827 cells were assessed using a
clonogenic assay. Apoptosis was measured by flow cytometry and EGFR signal
transduction was evaluated by western blotting. RESULTS: The Dq - quasi-threshold
dose, the dose at which the straight portion of the survival curve, extrapolated
backward, cuts the dose axis drawn through a survival fraction of unity - after
radiation-alone and after combination treatment were 0.41+/-0.09 Gy and 0.08+/
0.11 Gy, respectively; thus indicating that combination treatment resulted in
supra-additive effects of radiation. There was no significant difference on the
D0 - final slope of the survival curve (the dose required to reduce the fraction
of surviving cells to 37% of its previous value) - between-radiation alone and
the combination treatment. Apoptosis significantly increased after the
combination treatment in comparison to what was observed after radiation-alone.
The expression of phosphorylated EGFR (pEGFR), phosphorylated ERK1/2 (pERK1/2)
and phosphorylated AKT (pAKT) after the combination decreased in comparison to
what was observed after radiation-alone. CONCLUSION: Gefitinib enhances
radiosensitivity of supra-additively HCC827 cells by inhibiting the activation of
the anti-apoptotic and proliferative signal transduction pathways.
PMID- 23155257
TI - Beneficial oncolytic effect of fiber-substituted conditionally replicating
adenovirus on human lung cancer.
AB - BACKGROUND: Adenovirus vectors have been utilized for a variety of cancer gene
therapy. The present study examined the oncolytic effect of adenovirus type 5
(Ad5) and fiber-substituted conditionally replicating adenovirus (CRAD) Ad5/F35
vectors on human lung cancer A549 cells (an epithelial adenocarcinoma cell line),
SBC-3 cells (a small-cell cancer cell line), and Lu-65 cells (a giant-cell lung
cancer cell line). MATERIALS AND METHODS: For adenovirus, the first mRNA/protein
to be made (~1 h after infection) is early region 1A (E1A). Ad5F35 and Ad5 CRAD
vectors containing the E1 gene, controlled by the human midkine promoter
(Ad5F35/MKp-E1 and Ad5/MKp-E1, respectively) were constructed. Reverse
transcription-polymerase chain reaction (RT-PCR), western blotting and cell
viability assays were carried out in cells transfected with Ad5/MKp-E1 and
Ad5F35/MKp-E1. RESULTS: Less expression of mRNA and protein for coxsackie and
adenovirus receptor (CAR), a cell surface target of Ad5, was found with lung
cancer cells as compared with the expression in human embryonic kidney 293
(HEK293) cells, but otherwise mRNA and CD46 protein, a cell surface target of
Ad35, was expressed in lung cancer cells as much as in HEK293 cells. Both Ad5/MKp
E1 and Ad5F35/MKp-E1 induced oncolysis of lung cancer cells in a viral particle
dependent manner, with more efficient advantage for Ad5F35/MKp-E1. CONCLUSION:
The results of the present study suggest that Ad5F35/MKp-E1 is more useful for
the gene therapy of human lung cancer than Ad5/MKp-E1 is.
PMID- 23155256
TI - EVI1 and MDS1/EVI1 expression during primary human hematopoietic progenitor cell
differentiation into various myeloid lineages.
AB - BACKGROUND AND AIM: Overexpression of ecotropic viral integration site 1 (EVI1)
is associated with aggressive disease in myeloid leukemia. We therefore studied
its expression and function in cluster of differentiation 34-positive (CD34(+))
primary human hematopoietic progenitor cells. MATERIALS AND METHODS: CD34(+)
cells were differentiated into various myeloid lineages using the appropriate
cytokines. EVI1 expression was measured by quantitative real time reverse
transcriptase-polymerase chain reaction (qRT-PCR) and intranuclear fluorescence
activated cell sorting (FACS). Experimental manipulation of EVI1 levels was
achieved using retroviral infection. RESULTS: EVI1 mRNA and its variant
myelodysplastic syndrome 1 (MDS1)/EVI1, which gives rise to a partially
antagonistic protein, were detectable in CD34(+) cells, but their levels declined
rapidly during differentiation into the granulocyte, monocyte, dendritic,
erythroid, and megakaryocyte lineages. Similarly, EVI1 protein levels decreased
during myeloid differentiation. Attempts to experimentally express EVI1 in
CD34(+) and U937 cells indicated that ectopic expression of EVI1 may cause growth
arrest, apoptosis and/or senescence of human hematopoietic cells. CONCLUSION:
EVI1 is expressed in human hematopoietic progenitor cells, but is down-regulated
during differentiation. Ectopic expression of EVI1 may activate cellular
safeguards against oncogene activation.
PMID- 23155258
TI - Phenotypic analysis of monocyte-derived dendritic cells loaded with tumor antigen
with heat-shock cognate protein-70.
AB - BACKGROUND/AIM: The cross-presentation system of tumor antigen by monocyte
derived dendritic cells (mo-DCs) has been observed under appropriate conditions.
Both CD14-negative and CD1a-positive phenotypes were critical in our previous
study. This study compared the phenotype of mo-DCs and identified the conditions
that favored T helper-1 (Th1) cytokine production after stimulation with the
hsc70 and NY-ESO-1 p157-165 epitope fusion protein (hsc70/ESO p157-165).
MATERIALS AND METHODS: The mo-DCs were induced from healthy donors. Their surface
markers and cytokine production were examined after stimulation with hsc70/ESO
p157-165. RESULTS: CD1a(+) and CD1a(-) mo-DCs were generated in half of the
healthy donors. The concentration of fetal calf serum in the culture medium was
critical for the induction of CD1a(+) DCs, which were able to produce interleukin
12 (IL-12), but not IL-10. Neutralizing IL-6 and IL-6R antibodies affected the
expression of CD1a. CONCLUSION: Anti IL-6 analogs may be effective adjuvants for
the development of mo-DC-based cancer vaccine.
PMID- 23155259
TI - Primary bone lymphomas thought to be osteomyelitis urgently demand a rapid
diagnosis in bone pathology.
AB - We describe in detail three cases of primary bone lymphoma (PBL), initially
treated as osteomyelitis of unknown etiology. These cases show which difficulties
can occur with diagnosing this entity and highlight the urgent need for rapid
diagnostic results in the field of bone pathology. Case 1: A 22-year-old man with
the very rare diagnosis of precursor B-lymphoblastic lymphoma in the tibia
(previously published). Case 2: A 13-year-old boy with an anaplastic large cell
lymphoma of the "os pubis". With initial diagnosis pointing to multifocal
osteomyelitis, histology of the left iliac crest revealed a florid/chronic
osteomyelitis. During clinical regression with a new osteolytic lesion, he
received treatment for chronic recurrent multifocal osteomyelitis. Case 3: A 60
year-old man with an anaplastic large cell lymphoma of the right sacrum,
accompanied by a putrid, florid/chronic osteomyelitis. At first, an incisional
biopsy revealed a florid/chronic osteomyelitis-only.
PMID- 23155260
TI - A study of serum biomarkers associated with relapse of cervical cancer.
AB - BACKGROUND/AIM: To discover candidate protein biomarkers in the serum of patients
with cervical cancer that differentiate between patients with relapse from those
who are tumor-free after primary treatment with (platinum-based chemo-)
radiation. PATIENTS AND METHODS: Surface-enhanced laser desorption/ionization
time-of-flight mass spectrometry (SELDI-TOF-MS) with cation exchange (CM10) and
hydrophobic/reverse-phase (H50) was used to examine 44 serum samples from
patients with advanced cervical cancer, primarily treated with (platinum-based
chemo-) radiation. RESULTS: Ten candidate biomarkers were identified in the serum
of 34 patients. Six candidate markers were elevated in patients with no relapse
and four were elevated in patients with relapse [p=0.007-0.11; area under the
curve (AUC)=0.70-0.75]. Masses of candidate biomarkers ranged from 2,022 to
116,165 Da. CONCLUSION: Patients with relapse from primary advanced cervical
cancer exhibit different serum protein expression profiles from those with no
relapse.
PMID- 23155261
TI - Clinical utility of transarterial infusion chemotherapy using cisplatin-lipiodol
emulsion for unresectable hepatocellular carcinoma.
AB - BACKGROUND: We evaluated the clinical efficacy of transarterial infusion
chemotherapy using a cisplatin-lipiodol emulsion for unresectable hepatocellular
carcinoma (HCC). PATIENTS AND METHODS: Fifty-seven patients with advanced HCC,
with no indications for surgical resection or local ablative therapy, such as
percutaneous ethanol injection and radiofrequency ablation, were enrolled in this
retrospective study. RESULTS: Twelve patients were treated with cisplatin-alone
at a dose of 65 mg/m(2) by infusion into the artery. Forty-two patients were
treated with the same dose of cisplatin suspended in 1-10 ml of lipiodol (C/LPD).
Cumulative survival rates in the cisplatin-treated group were 46.2% at one year,
and 18.5% at two years, whereas these in the C/LPD group were 81.6% and 44.4%,
respectively, with a significant difference between the two groups (p<0.01). In
the cisplatin-treated group (n=13), no (0%) patients had a complete response
(CR), two (15%) a partial response (PR), three (23%) no change (NC), and eight
(62%) progressive disease (PD). In the C/LPD group (n=44), four (9%) patients had
CR, 16 (35%) PR, 12 (26%) NC, and 12 (26%) PD. CR and PR were seen in 15% of the
cisplatin-treated group and in 44% of the C/LPD group. C/LPD was significantly
more effective than cisplatin-alone (p=0.039). Some patients showed tumor
response to C/LPD after intra-arterial infusion of low-dose 5-fluorouracil.
CONCLUSION: C/LPD produced superior effects compared to cisplatin-alone for
unresectable HCC, causing no major side-effects, and increasing the survival
rate.
PMID- 23155262
TI - Photodynamic therapy using talaporfin sodium (Laserphyrin(r)) for bile duct
carcinoma: a preliminary clinical trial.
AB - The efficacy of adjuvant photodynamic therapy (PDT) using the new
photosensitizer, talaporfin sodium (TPS), was assessed in 7 patients with bile
duct carcinoma (BDC). The 664-nm semiconductor laser (100 J/cm(2)) was applied
through endoscopy to the tumor lesion within 6 h after injection of TPS. Cases
included three non-resectable and 4 resected BDC with remnant cancer cells at the
bile duct stump. Radiated lesions exhibited mild inflammatory responses. Locally
advanced tumor occluding bile duct was relieved by PDT and patency was maintained
for 16 months. Two patients developed mild photodermatitis but no severe
morbidity. One patient died of other disease, and two patients died of liver
metastasis within 6 months, but local recurrence was not observed. Three patients
maintained cancer-free survival for 6-13 months. One patient survived with good
status for 24 months. Adjuvant TPS-PDT is a safe and useful treatment for local
control of BDC. Compared to the conventional PDT, the patient's quality of life
is remarkably improved.
PMID- 23155263
TI - Medullomyoblastoma: a case report and literature review of a rare tumor entity.
AB - BACKGROUND: Medullomyoblastoma (MMB) is a very rare medulloblastoma (MB) variant
consisting of primitive neuroectodermal cells intermixed with cells featuring
myogenic differentiation. MMBs are a subtype of primitive neuroectodermal
neoplasm (PNET) predominantly occurring in children. CASE REPORT: We describe a
case of a one-year-old girl who presented with headache, emesis and ataxia. The
symptoms had started seven weeks before hospital admission. Magnet resonance
imaging of the brain was performed, and revealed a lesion with a maximal diameter
of 5 cm, located in the cerebellum close to the vermis. Histologically, the
poorly-differentiated lesion was diagnosed as a type of PNET, but it was the
immunohistochemical staining that assured the diagnosis of MMB. RESULTS:
Immunohistochemistry and interphase fluorescence in situ hybridization (I-FISH)
were performed on formalin-fixed paraffin-embedded tissue. FISH did not reveal
any amplification of CMYC or NMYC. No nuclear expression of beta-catenin was
detectable. DISCUSSION: Since MMB is a very rare tumor entity, standard treatment
today is the same as that for conventional MB due to the lack of larger study
series. Some authors assume that MMBs behave especially aggressive in comparison
to conventional MBs. Therefore, new treatment regimes should be tested to
optimize the prognosis of MMB. Further data is needed to determine the
differences between MB and MMB.
PMID- 23155264
TI - Focus on the actual clinical target volume irradiated with intraoperative
radiotherapy for breast cancer.
AB - AIM: Intraoperative radiotherapy (IORT) has been investigated as an exclusive
adjuvant treatment option for early-stage breast cancer (BC). We analysed our
experience on the technical aspects of this innovative approach in terms of
identification of breast volume actually to be treated during IORT. PATIENTS AND
METHODS: A total of 315 patients at low risk of breast cancer recurrence
underwent IORT as exclusive treatment after breast-conservative surgery. To
evaluate the breast volume actually irradiated with IORT, we considered a sample
of eight patients, chosen retrospectively as having enough clips to identify the
tumour bed and IORT site in computed-tomography (CT). The clinical target volume
(CTV) was assessed for each patient with two different methods: the first, cc
IORT, was considered during surgery according to the chosen collimator diameter
and glandular thickness, while the second, cc-CT, was evaluated through computed
tomography performed after surgery. The cc-CT CTV was obtained by contouring the
cc-IORT on the CT section on the basis of the clips placed by the surgeon on the
resection margins. RESULTS: In our experience, the 5-cm (50%) and the 6-cm (36%)
diameter collimators have been the ones, used the most. The diameter of the
collimator used did not appear to adversely affect the satisfactory aesthetic
result. The comparison between CTVs showed that glandular breast volume contoured
with CT (cc-CT) appeared to be three fold larger than the target identified at
surgery and included in the area of chosen collimator (cc-IORT). CONCLUSION: The
actual volume of breast gland irradiated with the IORT procedure appears to be
larger than expected. This may be due to the area being prepared for IORT by
placing tissue compactly.
PMID- 23155265
TI - Semi-automated volumetric quantification of tumor necrosis in soft tissue sarcoma
using contrast-enhanced MRI.
AB - BACKGROUND: Response Evaluation Criteria in Solid Tumors (RECIST)-defined
measurements are limited when evaluating soft tissue sarcoma (STS) response to
therapy. Histopathological assessment of STS response requires a determination of
necrosis following resection. A novel semi-automated technique for volumetric
measurement of tumor necrosis, using enhanced magnetic resonance imaging (CE
MRI), is described. PATIENTS AND METHODS: Eighteen patients with STS were treated
with neoadjuvant therapy and then resected. CE-MRI, obtained prior to resection,
were evaluated by two observers using semi-automated segmentation. Tumor volume
and percent necrosis was compared with histology and RECIST measurements.
RESULTS: The median percent necrosis, determined histologically and from CE-MRI,
was 71.9% and 67.8%, respectively. Accuracy of these semi-automated measurements
was confirmed, being statistically similar to those obtained at histopathological
assessment of the resected tumor. High Intra-class correlation co-efficients
suggest good inter-observer reproducibility. Tumor necrosis did not correlate
with the RECIST measurements. CONCLUSION: Semi-automated determination of tumor
volume and necrosis, using CE-MRI, is suggested to be accurate and reproducible.
PMID- 23155267
TI - Isolation and characterization of bone marrow-derived progenitor cells from
malignant gliomas.
AB - BACKGROUND: Malignant gliomas are highly-vascularised tumours. Neoangiogenesis is
a crucial factor in the malignant behaviour of tumour and prognosis of patients.
Several mechanisms are suspected to lead to neoangiogenesis, one of them is the
recruitment of multipotent progenitor cells towards the tumour. Factors such as
Vascular endothelial growth factor-A (VEGF-A) were described to recruit bone
marrow-derived endothelial progenitor cells (EPCs) to the glioma stroma and
vasculature. Little is known about isolating EPCs from normal or malignant
tissues. MATERIALS AND METHODS: In this study, we addressed the topic of
characterization of tumour-isolated EPCs and re-defined the clonal relationship
between EPCs and hematopoietic stem cells (HSCs) in gliomas. We first checked
public gene expression data of glioma for putative marker expression, pointing
towards a prevalence of EPCs and HSCs in glioma. Immunohistochemical staining of
glioma tissue confirmed the higher expression of these progenitor markers in
glioma tissue. EPCs and HSCs were consequently isolated and characterized at the
phenotypic and functional levels. We applied a new isolation method, for the
first time, to specimen from patients with high grade glioma including seven
grade IV glioblastoma, five-grade III astrocytoma, and three grade III
oligoastrocytoma. RESULTS: In all samples, we were able to isolate the tumour
derived EPCs, which were positive for characteristic markers: CD31, CD34 and
VEGFR2. The EPCs formed capillary networks in vitro and had the ability to take
up acetylated low-density lipoprotein. Glioma-derived HSCs were positive for CD34
and CD45, but they were unable to form a capillary network in vitro. These
findings on tumour-derived EPCs/HSCs were in concordance with the results,
derived from peripheral blood of healthy volunteers. CONCLUSION: In our study, we
established a new method for EPC/HSC isolation from human gliomas, defined the
contribution of EPCs and HSCs to the tumour tissue, and highlighted the intense
in vivo tumour host interaction.
PMID- 23155266
TI - Uncertainty in the utility of immunohistochemistry in mismatch repair protein
expression in epithelial ovarian cancer.
AB - BACKGROUND: Utility of immunohistochemistry (IHC) for mismatch repair (MMR)
protein expression has been demonstrated in colorectal cancer but remains
incompletely defined in ovarian cancer. We evaluated MMR protein expression in
three population-based samples of epithelial ovarian cancers. MATERIALS AND
METHODS: IHC staining was performed on full-section (FS) or tissue microarray
(TMA) slides for MLH1, MSH2, and MSH6 expression. RESULTS: Out of 487 cases, 147
and 340 were performed through FS and TMA, respectively. Overall, Loss of
Expression (LoE) of at least one MMR protein was observed in 12.7% based on an
expression score of <=3 (on a scale of 9). Notably, LoE was significantly higher
in TMAs (17.9%) compared to FS cases (0.7%) (p<0.001). CONCLUSION: A substantial
proportion of epithelial ovarian cancers have a loss of MMR protein expression.
Protein expression results vary significantly by the tissue sampling methodology
utilized, raising concerns about the clinical utility of this test for ovarian
tumors.
PMID- 23155268
TI - Epistaxis secondary to panitumumab in a patient with colon cancer.
AB - Epidermal growth factor receptor inhibitors (EGFRIs) have become an integral part
of therapy for many types of solid malignancy, including colorectal cancer. The
drug class has proven to be effective without causing many of the side-effects
associated with chemotherapy or other growth factor receptor inhibitors.
Epistaxis, a common side-effect of Vascular Endothelial Growth Factor inhibitors,
is rarely noted with EGFRIs. We report on one patient, a 51-year-old man with
metastatic colon cancer, who developed severe epistaxis with the use of
panitumumab. We discuss the other reported cases of EGFRIs causing epistaxis and
hypothesize on possible mechanisms by which this drug class might cause mucosal
bleeding.
PMID- 23155269
TI - Alpha-fetoprotein-producing carcinoma of the renal pelvis exhibiting hepatoid and
urothelial differentiation.
AB - Neoplasms commonly associated with alpha-fetoprotein (AFP) production are
hepatocellular carcinomas and some germ cell tumors, typically yolk sac tumor.
Rare tumors of visceral origin may also be associated with AFP production and
those exhibiting a distinctive morphology are now known as hepatoid
adenocarcinomas. To date, eight such tumors have been reported from the bladder
and a further four from the renal pelvis. We report a unique case of a mixed
hepatoid adenocarcinoma and urothelial carcinoma of the renal pelvis and ureter,
in which both components were found to express AFP. An 84-year-old woman with a
serum AFP level of 701 ng/ml was found to have advanced high-grade renal pelvi
calyceal and ureteral urothelial carcinoma exhibiting focal hepatoid
adenocarcinoma differentiation. Both components displayed strong immunostaining
for AFP. The patient was treated by radical nephro-uretectomy and postoperatively
the serum AFP level declined to normal at a rate commensurate with its biological
half-life. The presence of AFP expression in both the urothelial and hepatoid
components of the tumor suggest that the molecular pathway changes associated
with AFP production precede the hepatoid differentiation of tumor cells.
PMID- 23155270
TI - Effect of breast cancer adjuvant therapies on potential biomarkers of pulmonary
inflammation.
AB - BACKGROUND: The aim of this study was to investigate the effect of breast cancer
adjuvant therapies on the levels of circulating surfactant protein-D (SP-D), C
Reactive protein (CRP) and soluble receptor for advanced glycation end-products
(sRAGE), as potential biomarkers of subclinical pulmonary inflammation. MATERIALS
AND METHODS: The soluble molecules were serially determined in 38 patients, prior
to the initiation of radiation therapy (RT) and during adjuvant treatment, using
immunoassays. RESULTS: Significantly higher levels of all three biomarkers were
observed in patients prior to the initiation of RT compared to healthy controls
(CRP: p<0.001, SP-D: p<0.05, sRAGE: p<0.05). SP-D levels exhibited a gradual
increase after RT and during follow-up (p<0.005). Patients treated with a
combination of RT and hormonal therapy presented a significant, but less
pronounced, increase in SP-D and a significant decrease in CRP compared to those
who did not receive hormonal therapy (p=0.0428 and p=0.0116, respectively).
Patients treated with a combination of RT and trastuzumab presented a significant
increase in SP-D levels (p=0.0310). CONCLUSION: The average rate of change in the
levels of circulating SP-D and CRP during postoperative irradiation and adjuvant
hormonal therapy suggests that the combined therapeutic regiment may potentially
exert important anti-inflammatory effects on the lung. On the contrary, combined
administration of RT and trastuzumab is likely to induce or provoke pulmonary
inflammation.
PMID- 23155271
TI - Prognostic significance of ERCC1, RRM1 and BRCA1 in surgically-treated patients
with non-small cell lung cancer.
AB - Chemotherapy is an important modality of treatment for non-small cell lung cancer
(NSCLC). Recent studies have shown that assessment of predictive molecular
markers could be helpful for estimation of the response rate to chemotherapy. The
aim of our study was to assess the relation of mRNA levels of DNA repair genes
excision repair cross-complementary group 1 (ERCC1), ribonucleotide reductase
subunit M1 (RRM1) and breast cancer 1 (BRCA1), in surgically-resected tumor
tissues from patients who underwent adjuvant chemotherapy, to the disease-free
interval (DFI) and overall survival (OS). We investigated if potential residual
tumor cells after resection reflect properties of the primary tumor and response
to chemotherapy according to the level of predictive markers with respect to
current knowledge. PATIENTS AND METHODS: We studied a group of 90 patients with
NSCLC who had undergone curative lung resection; 59 of them were subsequently
treated with adjuvant chemotherapy, DFI and OS were evaluated only in this
subgroup. Quantitative estimation of mRNA of selected genes in paired (tumor and
control)-lung tissue samples was performed by real-time reverse transcription
polymerase chain reaction (RT-PCR). RESULTS: We found a significantly lower mRNA
expression of ERCC1 (p<0.001) and RRM1 (p=0.023) in NSCLC tumor tissues compared
to normal lung tissues. Comparing expression in histological subtypes, we
recorded higher mRNA expression of ERCC1 (p=0.021), RRM1 (p=0.011) and BRCA1
(p=0.011) in adenocarcinoma than in squamous cell carcinoma (SCC). Differences in
DFI and OS were found only in specific subgroups according to tumor type and
stage. We found longer OS for patients with adenocarcinoma with higher expression
of the RRM1 mRNA (p=0.002), and for patients with SCC with higher expression of
the BRCA1 mRNA (p=0.041). In patients with NSCLC of stage III, we found longer
DFI in those with higher expression of RRM1 (p=0.004) and ERCC1 (p=0.038).
CONCLUSION: Patients who had been treated with adjuvant chemotherapy and had
shown lower expression of repair genes had adverse prognosis. We observed that
the assessment of DNA repair gene level in primary tumors treated by surgical
resection had prognostic significance and did not predict response to adjuvant
chemotherapy.
PMID- 23155272
TI - Borderline serous papillary tumour of the testis: a case report and review of the
literature.
AB - Borderline serous tumour of the testis and paratestis is an uncommon entity. We
report a case of borderline serous tumour of a 59-year-old male, who presented
with a right testicular swelling which was clinically suspicious of carcinoma.
Radical orchidectomy was performed and a cystic lesion was identified in the
testis. Macroscopically the tumour was composed of a unilocular cyst with
excrescences in the inner surface. The histological features were identical to
the ovarian counterpart of borderline serous papillary tumour. The excrescences
were formed by stratified columnar epithelium, which exhibited mild nuclear
pleomorphism and mitotic activity, with a fibrovascular core and scattered
psammoma bodies. There was no lymphovascular or stromal invasion. The lesion was
surrounded by a dense fibrous wall. On immunohistochemistry, the lining
epithelial cells expressed cytokeratin AE1/AE3 but not carcinoembryonic antigen
or calretinin. Following the removal of the tumour, the patient was followed up
and no recurrence or metastasis has occurred to date. This case highlights the
need for clinicians and pathologists to be aware of this rare entity and to
develop the best approach for patient management.
PMID- 23155273
TI - Along the pituitary-testis-prostate axis, serum total testosterone is a
significant preoperative variable independently contributing to separating the
prostate cancer population into prostatectomy Gleason score groups.
AB - AIM: To investigate, along the pituitary- testis- prostate axis, the potential of
preoperative serum TT in contributing to defining separate prostatectomy Gleason
score (pGS) groups of the prostate cancer (PC) population. MATERIALS AND METHODS:
The data of 126 patients operated on for PC were retrospectively reviewed. No
patient had previously received 5alpha-reductase inhibitor, luteinizing hormone
(LH)-releasing hormone analogs or testosterone replacement treatment. The patient
population was grouped according to the prostatectomy Gleason score (pGS) as
6=3+3, 7=3+4, 7=4+3 and 8-10. Twelve variables were simultaneously investigated
in each group: age, prolactin (PRL), follicle stimulating hormone (FSH), LH,
total testosterone (TT), free testosterone (FT), estradiol (Er), prostate
specific antigen (PSA), percentage of prostate biopsy positive cores (P+), biopsy
Gleason score (bGS), overall cancer volume estimated as percentage of prostate
volume (V+) and prostate weight (Wi). Univariate analysis of variance (ANOVA),
multivariate analysis of variance (MANOVA) and multivariate discriminant analysis
were the statistical methods used for evaluating the data. RESULTS: There were 38
patients in pGS 6=3+3, 57 in pGS 7=3+4, 15 in pGS 7=4+3 and 16 in pGS 8-10. ANOVA
showed that bGS (p<0.0001), P+ (p<0.0001), V+ (p<0.0001), PSA (p=0.02), Wi
(p=0.001) and TT (p=0.04) were significantly different in the four pGS groups.
MANOVA tests showed that only bGS (p<0.0001) and TT (p=0.005) were the
significant variables that individually and independently contributed a
significant amount to separation of the four pGS groups of the PC population.
Multivariate discriminant analysis confirmed that TT (p=0.005) and bGS (p<0.0001)
were the only variables that independently and significantly contributed to
separating the pGS groups. CONCLUSION: along the pituitary- testis- prostate
axis, serum TT is a significant preoperative variable that independently
contributes to separating the prostate cancer population into pGS score groups.
Pretreatment baseline serum TT levels should be measured for their inclusion in
nomograms and future neural networks to be considered in the patient population
diagnosed with PC.
PMID- 23155274
TI - Radical nephrectomy with transperitoneal subcostal incision for large and locally
advanced tumors of the right kidney.
AB - BACKGROUND: Several surgical approaches have been used for radical nephrectomy
for large and locally advanced tumors of the right kidney. AIM: To present our
experience with radical nephrectomy using a right subcostal incision with a
transperitoneal approach in patients with very large tumors of the right kidney.
PATIENTS AND METHODS: Between 2003 and 2010, 34 patients with very large tumors
of the right kidney were submitted to surgery. Eighteen patients underwent a
transperitoneal approach with a right subcostal incision (intervention group) and
16 patients were operated on with retroperitoneal flank incision (control group).
RESULTS: No significant complications during surgery were observed in the
intervention group; two patients needed blood transfusions of 300 cc during the
first postoperative day. In the control group, injury of the renal vein or
inferior vena cava (IVC) was a relatively common complication; five patients
needed blood transfusions of 300 cc during the first postoperative day.
CONCLUSION: A transperitoneal right subcostal incision for radical nephrectomy in
patients with large and locally advanced tumors of the right kidney seems to
offer better access to the renal pedicle, and to the great vessels of the area as
well as better exposure of the organs of the abdominal cavity. This approach
could be more useful in cases in which liver involvement is possible.
PMID- 23155275
TI - c-MYC amplification in mucinous gastric carcinoma: a possible genetic alteration
leading to deeply invasive tumors.
AB - BACKGROUND: Patients with mucinous gastric carcinoma (MGC) usually have a poor
prognosis, largely due to the advanced stage of disease. In this study, we
evaluated the effects of c-MYC amplification on tumor stage and disease-specific
survival of 128 patients with MGC and compared the results with those of 302
patients with non-mucinous gastric carcinoma (non-MGC). PATIENTS AND METHODS: Two
color fluorescence in situ hybridization (FISH) for c-MYC was performed on 430 GC
samples. Real-time quantitative polymerase chain reaction (q-PCR) analysis for c
MYC was also performed after tumor microdissection. RESULTS: c-MYC amplification
was found in 10.2% of MGCs and 6.0% of non-MGCs. c-MYC amplification was more
frequently found in MGCs of higher tumor stage than in MGCs of lower stage
(p=0.038). c-MYC amplification in MGC was correlated with greater invasion depth
(p=0.007). The mean survival time of patients with c-MYC amplification was
shorter than that of patients without c-MYC amplification in MGC. Real-time q-PCR
results showed that the calculated c-MYC/GAPDH ratios were higher in c-MYC
amplified MGC than in c-MYC-non-amplified MGC. CONCLUSION: This study showed that
c-MYC amplification in MGC is highly correlated with advanced stage and deeply
invasive MGC. This suggests that c-MYC amplification in MGC could be a possible
genetic alteration contributing to the frequent presentation of advanced-stage
MGC.
PMID- 23155276
TI - Initial safety and outcomes of miriplatin plus low-dose epirubicin for
transarterial chemoembolisation of hepatocellular carcinoma.
AB - AIM: To evaluate the initial safety and efficacy of combination therapy using
miriplatin plus low-dose epirubicin for transarterial chemoembolisation (TACE) of
unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Patients who
underwent TACE using miriplatin plus epirubicin (n=48) and control patients who
underwent TACE using miriplatin-alone (n=51) were included in this study.
RESULTS: The objective response rate in the miriplatin plus epirubicin group
(91%) was significantly higher than that in the miriplatin group (74%, p=0.024).
Concomitant use of miriplatin and epirubicin was an independent factor associated
with higher objective response rate (hazard ratio=0.18; p=0.012). Overall
incidence adverse events was not significantly different between the miriplatin
plus epirubicin group (50%) and the miriplatin group (49%, p=0.575). CONCLUSION:
TACE using miriplatin plus low-dose epirubicin was associated with an increased
objective response rate and comparable adverse effects compared to TACE using
miriplatin-alone.
PMID- 23155277
TI - Quality of life and sexuality of patients after treatment for gynaecological
malignancies: results of a prospective study in 55 patients.
AB - AIM: To assess the sexuality and quality of life (QoL) of women with
gynaecological malignancies after multimodal therapy. MATERIALS AND METHODS: This
is a prospective analysis of the sexual status among women after treatment for
gynaecological malignancies. Validated questionnaires-female sexual function
index (FSFI-d), a semi-structured questionnaire and the quality of life score
SF12, were applied. RESULTS: Overall, 55 patients (median age=61, range=22-74
years) were enrolled. The cancer diagnoses were 54% ovarian, 26% breast, 13%
cervical, 6% vulvar and 2% endometrial cancer. Twenty patients (55.6%) claimed
experiencing changes in their sexuality after cancer treatment. The main reasons
for this impairment were distorsion of their self image (45%; n=9), dry vaginal
mucosa (25%; n=5), fear of physical harm (20%; n=4) and pain during sexual
intercourse (20%; n=4). Forty percent of the patients gave no information about
their sexuality after cancer therapy. Patients with cervical, endometrial or
vulvar cancer had significantly higher changes in their sexuality compared to
patients with ovarian cancer even after adjusting for age, recurrence rate and
partnership status. The evaluation of SF12 revealed significantly higher
psychological functional scores with increasing age. Patients who reported
changes of their sexuality were also shown to have a lower overall SF12 score.
CONCLUSION: Evaluation of sexuality and self image perception after cancer
treatment is an unmet need and needs to be addressed in women with gynaecological
malignancies. Further studies are warranted to assess the influence of the
various types of cancer therapies in regard to their effect on sexuality and
quality of life.
PMID- 23155278
TI - Early relapse is associated with high serum soluble interleukin-2 receptor after
the sixth cycle of R-CHOP chemotherapy in patients with advanced diffuse large B
cell lymphoma.
AB - The clinical significance of serum soluble interleukin-2 receptor (sIL2R) levels
was retrospectively assessed in patients with advanced diffuse large B-cell
lymphoma (DLBCL). Twenty-one patients, who were newly-diagnosed with advanced
DLBCL (stage III and IV) between 2006 and 2009, were evaluated. The median follow
up period was 37 months. All patients received 6-8 cycles of chemotherapy with
rituximab in combination with doxorubicin, cyclophosphamide, vincristine, and
prednisolone (CHOP)-like regimens and attained complete remission. Although all
patients reached complete remission, six patients experienced disease relapse
within 1 year after treatment completion. The overall survival was significantly
poorer in patients with relapse than in patients with durable remission. The
sIL2R levels after the sixth cycle of treatment were significantly higher in the
relapse group than in the non-relapse group. Thus, the present study suggests
sIL2R levels to be a valuable predictor for the prognosis of patients with
advanced DLBCL.
PMID- 23155279
TI - Percutaneous radiofrequency ablation therapy for recurrent hepatocellular
carcinoma.
AB - AIM: To compare the overall survival (OS) in patients without recurrent
hepatocellular carcinoma (HCC) after initial radiofrequency ablation (RFA) and in
those with recurrence, treated with repeat-RFA. PATIENTS AND METHODS: We compared
OS between patients without recurrence (group A; n=150) and those with recurrence
treated with repeat-RFA (group B; n=130). RESULTS: One-, 3- and 5-year OS after
initial RFA was 92.6%, 84.1% and 81.0%, respectively, in group A, and 99.0%,
84.1% and 61.8% in group B (p=0.296). There was no significant difference in OS
between group A patients and patients with a single recurrent HCC (p=0.834). On
multivariate analysis, serum albumin >3.5 g/dl and first HCC recurrence,
comprising of two or three nodules were significant predicting factors of poorer
OS. CONCLUSION: Even if HCC recurs after initial RFA, survival comparable to that
of patients without recurrence can be achieved in patients with a single
recurrent tumor treated with repeat-RFA.
PMID- 23155280
TI - Metronomic cyclophosphamide with cisplatin and bevacizumab: a new
chemotherapeutic regimen for refractory anaplastic ependymoma.
AB - Anaplastic ependymoma is a rare brain tumor, induced both in the brain and the
spine. The treatment relies on surgery and radiotherapy. Upon failure of these
treatments, chemotherapy has modest effects. Here, we report two cases of
anaplastic ependymoma with prolonged radiological and clinical responses to a
metronomic cyclophosphamide, cisplatin and bevacizumab regimen. Two patients with
anaplastic ependymoma, refractory to surgery and radiotherapy were proposed for a
chemotherapeutic treatment. These patients had both spina and brain nodules.
Neurological symptoms included arm deficiencies and paraparesia. RESULTS: Six
cycles of the metronomic cyclophosphamide (50 mg per day, daily), cisplatin (100
mg/m(2) every four weeks) and bevacizumab (10 mg/kg every two weeks), as a
chemotherapeutic regimen, induced both radiological response on magnetic
resonance imaging and clinical response with neurological deficiency regression.
At one year, the patients were still under maintenance therapy with metronomic
cyclophosphamide and cisplatin. This treatment still continues to control tumor
progression and symptoms. CONCLUSION: This is the first report showing an
impressive efficacy of metronomic the cyclophosphamide, cisplatin and bevacizumab
chemotherapeutic regimen for the treatment of refractory anaplastic ependymoma.
PMID- 23155281
TI - Talc pleurodesis as surgical palliation of patients with malignant pleural
effusion. Analysis of factors affecting survival.
AB - Malignant pleural effusion (MPE) is common in most patients with advanced cancer,
especially in those with lung cancer, metastatic breast carcinoma and lymphoma.
This complication usually leads patients to suffer from significant dyspnea,
which may impair their mobility and reduce their quality of life. In patients
with MPE, several interventions have been shown to be useful for palliation of
the symptoms, including talc pleurodesis. The aim of this study was to evaluate
prognostic factors for survival of patients with symptomatic MPE who underwent
palliative video-assisted thoracoscopic (VATS) talc pleurodesis. Thirty-five
patients with MPE underwent VATS, evacuation of the pleural fluid and talc
pleurodesis with large-particle talc. There were 22 (62.9%) males and 13 (37.1%)
females, with an overall median age of 69 years (range 42-81 years). The main
causes of MPE were non-small cell lung carcinoma, breast or ovarian cancer and
malignant pleural mesothelioma. The age did not differ (p=0.88) between men
(68.6+/-11.6 years) and women (68.0+/-8.7 years). The mean quantity of pleural
effusion was 2005.7+/-1078.9 ml, while the overall survival was 11.2+/-8.9
months. We did not find any relationship between survival and gender (log-rank
test, p=0.53) or underlying malignancy associated with MPE (p=0.89, 0.48 and 0.36
for secondary cancer, lung cancer and mesothelioma, respectively). Similarly, no
correlation was found between survival and age of the patients (Cox's regression,
p=0.44) or quantity of pleural effusion (p=0.88). Our results show that the
prognosis of patients after talc pleurodesis is independent of age, gender, type
of malignancy and amount of pleural effusion, thus, suggesting the utility of
treating all patients with symptomatic MPE early.
PMID- 23155282
TI - Papillary-serous adenocarcinoma of the uterine cervix during tamoxifen therapy
after bilateral breast cancer.
AB - BACKGROUND: Papillary-serous adenocarcinoma (PSCC) is a very rare subtype of
cervical cancer. To our knowledge, this is the first report on PSCC of the
uterine cervix following bilateral breast cancer. CASE REPORT: A 61-year-old
Caucasian woman underwent conserving surgery of both breasts at the age of 57
years, because of bilateral invasive ductal carcinoma. Radiation and tamoxifen
treatment followed. Routine surveillance examinations, including pelvic
examination, Papanicolaou (Pap) smear, and transvaginal ultrasound, were
uneventful. Recently, a small contact-bleeding mass of the cervix was found. The
Pap smear was II (reactive); HPV-DNA test was negative. The biopsy of the mass
revealed PSCC with a high expression of p53, carcinoembryonic antigen (CEA), and
Ki67 (50%). Staining for estrogen receptor (ER), progesterone receptor (PR), and
vimentin was negative. The serum carbohydrate antigen 125 (CA-125) reached 159
U/ml. The patient was treated with radical hysterectomy, bilateral salpingo
oophorectomy, and pelvic and paraaortic lymphadenectomy. A poorly-differentiated
papillary-serous, non-secretory adenocarcinoma, pT1b1, pN0 (0/44), pM0, G3, R0,
V0, L0, was confirmed. According to the German recommendations for early-stage
cervical cancer, the patient received no adjuvant treatment. Currently, the
patient is free of relapse 38 months after the diagnosis of cervical cancer and
87 months after that of breast cancer. CONCLUSION: Immunohistochemistry is
helpful in diagnosing rare entities. This case adds further evidence that the
prognosis for early-stage PSCC is probably not poorer than that for other
cervical adenocarcinomas.
PMID- 23155283
TI - Neuroendocrine carcinoma of the breast--diagnostic and clinical implications.
AB - BACKGROUND: Neuroendocrine breast carcinomas (NEC) are rare. Carcinomas with
mixed composition often behave differently from 'pure' histological types, and
the prognosis is determined by the proportion of the more aggressive tumour. The
molecular classification helps in making therapeutic decisions. CASE REPORT: A 56
year-old Caucasian woman with palpable and preoperatively biopsied breast tumour
was treated with breast-conserving surgery. The histological specimen revealed a
17-mm invasive carcinoma with an equal proportion of neuroendocrine and invasive
ductal differentiation, accompanied by peritumoural ductal carcinoma in situ. TNM
classification was pT1c(is), pN0 (0/1sn), G3, L0, V0, Pn0, R0. The diagnosis was
enhanced by immunohistochemistry: high positivity for synaptophysin, neuron
specific enolase (NSE), neural cell adhesion molecule (CD56), Ki-67
(proliferation index 46%), estrogen receptor (ER) and progesterone receptor (PR),
negative for Her-2-neu and cytokeratin 5/6, resulting in diagnosis of the
molecular 'luminal B' subtype. Radiation and adjuvant chemotherapy with six
cycles of 5-fluorouracil, epirubicin and cyclophosphamide, followed by tamoxifen
and subsequent exemestane for five years, were recommended. CONCLUSION:
Immunohistochemistry plays a crucial role in the diagnosis of rare cancer
subtypes. NEC is characterized by high biological aggressiveness. Molecular
classification facilitates therapeutic decisions.
PMID- 23155284
TI - Pelvic radiotherapy after renal transplantation.
AB - BACKGROUND: After renal transplantation, patients have a higher incidence of
developing cancer necessitating pelvic radiotherapy, but there is a lack of data
for such therapy in this patient group. PATIENTS AND METHODS: Nine patients with
pelvic renal transplants were treated with pelvic radiotherapy between 04/2002
and 06/2011. Treatment was carried out for prostate (n=4), rectal (n=2), and anal
cancer (n=1), osseous metastasis (n=1), and Hodgkin's disease (n=1). The mean age
of the transplants was 12.6 years. RESULTS: The mean total dose to the target
volume was 60.2 Gy, the mean maximum dose to the transplant was 10.0 Gy, with a
mean dose of 2.1 Gy. The mean creatinine clearance before start of radiotherapy
was 48.9 ml/min. After a mean follow-up of 23 months, no patient showed failure
of the transplant and the mean creatinine clearance was 64.2 ml/min. CONCLUSION:
Using modern radiotherapy techniques, low doses to the transplant can be achieved
without compromising target treatment and without transplant failure. A mean dose
of <4 Gy seems to be well-tolerated by the graft.
PMID- 23155285
TI - Prognostic value of preoperative metabolic tumor volumes on PET-CT in predicting
disease-free survival of patients with stage I non-small cell lung cancer.
AB - BACKGROUND: This study aimed to determine the relationship between the pre
operative metabolic tumor volume (MTV) and the disease-free survival (DFS) of
patients with stage I non-small cell lung cancer (NSCLC) using F-18 2-fluoro-2
deoxy-D-glucose (FDG) positron-emission tomography-computed tomography (PET-CT)
scanning. MATERIALS AND METHODS: Data from sixty patients with stage I NSCLC who
had undergone preoperative F-18 FDG PET-CT scanning were retrospectively
analyzed. The early and late maximum standardized uptake values (eSUVm and lSUVm,
respectively) were measured from attenuation-corrected F-18 FDG PET-CT images.
Three MTV segmentation methods were applied as an isocontour at an early SUV of
2.5 (MTV2.5) or using fixed thresholds of either 40% (MTV40%) or 50% (MTV50%) of
the maximum intratumoral F-18 FDG activity. DFS was compared by employing the
Kaplan-Meier method, using the median values as cutoffs for each parameter. The
log-rank test and Cox regression were performed to explore the effect of the
different MTV variables on DFS. Time-dependent receiver operating characteristic
(ROC) curves were created to evaluate the predictive performance. RESULTS: During
a median follow-up duration of 24 months, two patients died of disease
progression, and 11 experienced recurrent tumors (eight intrathoracic tumors, two
distant metastasis, and one both types of recurrences). The univariate analyses
showed that pathological stage 1B, histological type of squamous cell carcinoma,
male sex, maximum tumor size over 2 cm, eSUVm, lSUVm, and MTV2.5 were associated
with reduced DFS. Patients who had tumors with large eSUVm or large lSUVm had a
significantly lower 2-year DFS, compared with patients who had smaller tumors
(65% vs. 96%, p=0.002; 63% vs. 96%, p=0.000). Patients with an MTV2.5 greater
than 9.8 ml had a lower 2-year DFS than those with an MTV of 9.8 ml or greater
(59 vs. 85%, p=0.02). However, multivariate analysis showed that lSUVm over 3.4
was the only parameter that exhibited an impact on DFS (p=0.05, hazard
ratio=10.7), and the observed influence was marginal. CONCLUSION: For patients
with stage I NSCLC treated with surgery, preoperative MTV parameters have a
limited prognostic value for predicting DFS.
PMID- 23155286
TI - Nuclear matrix protein 22 for bladder cancer detection: comparative analysis of
the BladderChek(r) and ELISA.
AB - AIM: To compare nuclear matrix protein 22 expression by BladderChek(r) and ELISA,
as urine-based assays for bladder cancer (BC) detection. PATIENTS AND METHODS:
Urine samples of 100 BC patients and 100 controls were analyzed. Comparative
statistical evaluations were based on sensitivity and specificity. RESULTS:
Seventy-one patients had primary and 29 recurrent BC. The sensitivity of
BladderChek(r) was significantly higher compared to ELISA in the overall cancer
cohort and in patients with primary BC (p<0.0001 and p=0.0001, respectively).
Both tests demonstrated significant correlation of sensitivities and tumor
stage/grade for the overall cancer cohort and for patients with primary BC. Both
tests had specificity values of 100% in healthy individuals. Specificity was 93%
for BladderChek(r) and 99% for ELISA in patients with benign diseases (p=0.048).
CONCLUSION: BladderChek(r) may be clinically more useful for BC detection. Due to
high specificity, BladderChek(r) could be used for high-risk screening. However,
due to its low sensitivity, BladderChek(r) cannot replace but only complement
cystoscopy for BC detection.
PMID- 23155287
TI - Preoperative chemoradiotherapy using cisplatin plus S-1 can induce downstaging in
patients with locally advanced (stage III) non-small-cell lung cancer.
AB - BACKGROUND: About 30% of patients with non-small cell lung cancer (NSCLC) have
locally advanced cancer (stage IIIA or IIIB) at the time of presentation. Many
institutions have reported treatment with preoperative chemoradiotherapy (PCRT)
followed by curative resection in patients with stage III NSCLC, but the optimal
therapeutic protocol for this group has not been established. PATIENTS AND
METHODS: Nineteen patients with stage III NSCLC were treated with PCRT, followed
by surgery at the Hamanomachi Hospital, Fukuoka, Japan from May 2000 to November
2011. We evaluated the effectiveness of PCRT for inducing downstaging using
mainly three chemoradiotherapy regimens; cisplatin plus Tegafur-Gimeracil
Oteracil Potassium (S-1), cisplatin plus Tegafur-Uracil (UFT), or
1,1'cyclobutanedicarboxylate (Carboplatin, CBDCA) plus paclitaxel, with
concurrent radiation therapy in 19 patients with stage III NSCLC. RESULTS: The
overall 5-year survival rate was 57.1%, which is higher than the average survival
rate for patients with stage III NSCLC in Japan. Among the regimens used, only
cisplatin plus S-1 with concurrent radiation therapy significantly induced
downstaging. There was a significant difference in survival time between the
downstaged and non-downstaged groups. However, there was no significant
difference in survival time between the S-1 plus cisplatin group and the other
groups combined, because of the short observation period for the S-1 plus
cisplatin group. CONCLUSION: PCRT using cisplatin plus S-1 with concurrent
radiation therapy is useful for inducing downstaging in patients with locally
advanced stage III NSCLC.
PMID- 23155288
TI - Feasibility of (18)F-fluorodeoxyglucose positron-emission tomography for
preoperative evaluation of biliary tract cancer.
AB - (18)F-Labeled fluorodeoxyglucose positron-emission tomography (FDG-PET), a
rapidly evolving functional imaging modality, has recently been shown to be
useful in the diagnosis and staging of various malignant tumors due to focal
uptake of FDG-labeled glucose in malignant cell populations. However, the role of
FDG-PET in the diagnosis and staging of biliary tract cancer is still
controversial and has not yet been fully evaluated. The aim of this study was to
determine the clinical importance of FDG-PET in the preoperative evaluation of
biliary tract cancer and retrospectively clarify the characteristics of false
negative and false-positive cases. We retrospectively analyzed data for 73
consecutive patients diagnosed with cancer of the biliary tract and were admitted
to the Department of Hepato-Biliary-Pancreatic Surgery at Kobe University
Hospital for treatment, from January 2007 to August 2009. Since the sensitivity,
specificity and positive predictive value (PPV) of FDG-PET in the diagnosis of
bile duct carcinoma are usually relatively high, FDG-PET is considered to be a
useful tool in diagnosing biliary tract cancer. FDG-PET also seems to be useful
in clinical decision-making, regarding treatment strategy, including surgery. Our
results showed that FDG-PET is highly sensitive in delineating the primary focus
of biliary cancer and is a useful tool in preoperative examination. A
disadvantage of FDG-PET is its inability to indicate small metastases and false
positive findings of inflamed gallbladder and bile duct lesions.
PMID- 23155289
TI - An immunoassay method for the pharmacokinetics of 5-fluorouracil in patients with
gastric cancer administered adjuvant chemotherapy.
AB - Conventional gas chromatography-mass spectrometry (GC-MS) was compared with a new
immunoassay method for measuring plasma (5-FU) concentrations in adjuvant
chemotherapy with TS-1 for patients with gastric cancer. TS-1 was administered
orally to patients after gastrectomy. Blood samples for pharmacokinetic analysis
were collected on the seventh day of treatment. The mean area under the time
concentration curve (AUC)(0-8), half-life (t(1/2)), and maximum drug
concentration (C(max)) obtained by the two methods were as follows: GC-MS, 847.9
MUg/ml/hr, 2.76 h, and 186.6 ng/ml; and immunoassay, 1311.2 MUg/ml/hr, 3.5 h, and
259.8 ng/ml. Significant correlations were observed for AUC(0-8) (p=0.0001),
C(max) (p=0.0007), and changes in the 5-FU concentration in blood over time
(p=0.018) for the two methods. Compared with the conventional GC-MS method, the
new immunoassay method provides similar results, but is simpler and results can
be obtained earlier. This method will be useful for monitoring the 5-FU
concentration in serum from patients with gastric cancer receiving TS-1.
PMID- 23155290
TI - Lysozyme is up-regulated in columnar-lined Barrett's mucosa: a possible natural
defence mechanism against Barrett's esophagus-associated pathogenic bacteria.
AB - BACKGROUND: Lysozyme is a natural antimicrobial enzyme that is up-regulated in
inflammatory diseases of the gastrointestinal tract. Pathogenic microbes have
recently been identified in the esophageal mucosa in patients with Barrett's
esophagus (BE). Lysozyme expression was evaluated in biopsies from patients with
BE. MATERIALS AND METHODS: Ninety-seven consecutive esophageal biopsies with
columnar-lined Barrett's mucosa (BM) were investigated: 16 had oxyntic gland-only
BM, 19 pyloric gland-only BM and 62, intestinal metaplasia BM. Twenty normal
gastric biopsies and 20 normal duodenal biopsies were included as controls.
Sections were stained with human lysozyme antiserum. RESULTS: Lysozyme was up
regulated in the neck glands in 94% of the biopsies with oxyntic gland-only BM,
in the pyloric gland in 79% of the biopsies with pyloric gland-only BM, and in
goblet cells in 65% of the biopsies with intestinal metaplasia BM. Goblet cells
with faint lysozyme expression were often found in glands overexpressing lysozyme
in mucous secretions in the lumen. When compared to controls, lysozyme was up
regulated in all three BM phenotypes (p<0.05). CONCLUSION: Lysozyme is up
regulated in BM. It is therefore, believed that lysozyme's up-regulation might
mirror a molecular mechanism of self-defence aimed to safeguard the BM against
the hostile pathogenic microbiota present in the esophageal microenvironment in
patients with BE.
PMID- 23155291
TI - Prognostic factors of unresectable pancreatic cancer treated with nafamostat
mesilate combined with gemcitabine chemotherapy.
AB - BACKGROUND: The aim of this study was to investigate prognostic factors of
survival for patients with unresectable pancreatic cancer treated with nafamostat
mesilate combined with gemcitabine chemotherapy. PATIENTS AND METHODS: The study
included 41 patients who were diagnosed with unresectable pancreatic cancer and
eligible for our clinical study of nafamostat mesilate, combined with gemcitabine
chemotherapy for unresectable pancreatic cancer between February 2007 and
November 2010 at Jikei University Hospital. We retrospectively investigated the
relation between patients' characteristics and overall survival using univariate
and multivariate analyses. RESULTS: In univariate analysis, absence of jaundice
(p=0.0365), presence of ascites with or without histological diagnosis of
carcinomatosis (p=0.0042), lymphocyte count >=2,000/MUl (p=0.0088), serum C
reactive protein >=1 mg/dl (p=0.014), serum carcinoembryonic antigen >=5 ng/ml
(p=0.0064) and serum CA19-9 >=500 U/ml (p=0.0164) were significant predictors of
poor overall survival. In multivariate analysis, absence of jaundice (p=0.0057),
presence of ascites with or without histological diagnosis of carcinomatosis
(p=0.0326), lymphocyte >=2,000/MUl (p<0.0001) and CA19-9 >=500 U/ml (p=0.0198)
were independent predictors. CONCLUSION: Jaundice, ascites, high lymphocyte count
and high serum CA19-9 levels are independent prognostic predictors for poor
overall survival of patients with unresectable pancreatic cancer treated with
nafamostat mesilate combined with gemcitabine chemotherapy.
PMID- 23155292
TI - Testicular sclerosing Sertoli cell tumor: an additional case and review of the
literature.
AB - Sertoli cell tumours are very rare testicular tumours accounting for 0.4-1.5% of
all testicular neoplasms. In the current report, we present a case of sclerosing
Sertoli cell tumour. The histology and clinical features were compared to those
of other Sertoli cell tumour subtypes in order to assess if the different
subtypes really represent distinct clinical and prognostic entities. The current
literature was also reviewed. Only 20 cases of sclerosing Sertoli cell tumours
have been encountered. Our case, a 38-year-old man represents the 21st case.
Distinction among Sertoli cell tumours is important not only histologically;
sclerosing Sertoli cell tumours have a distinct clinical behaviour and prognosis,
different from those of classic and large-cell calcifying Sertoli cell tumours.
Pathologists and urologists should know and understand all the types of Sertoli
cell tumours in order to be able to choose the correct therapeutical approach
when they encounter these tumours.
PMID- 23155297
TI - Retraction. Aberrant methylation to heparan sulfate glucosamine 3-O
sulfotransferase 2 genes as a biomarker in colorectal cancer.
PMID- 23155293
TI - Improved quality of life in patients with malignant pleural effusion following
videoassisted thoracoscopic talc pleurodesis. Preliminary results.
AB - Malignant pleural effusion (MPE) is a common, debilitating complication of
several types of advanced malignancy, which may significantly reduce the quality
of life of patients. There are several options to treat MPE, including
thoracentesis, placement of a long-term indwelling pleural catheter and chemical
pleurodesis. The best treatment is still debated, but talc remains the agent of
choice to achieve pleurodesis. Forty-six patients (28 men and 18 women; median
age 67 years, range 47-82 years) with MPE related to different malignancies
underwent video-assisted thoracoscopy talc pleurodesis. There were 26 (56.5%)
patients with non-small cell lung cancer, 8 (17.4%) with breast cancer, 7 (15.2%)
with pleural mesothelioma and 5 (10.9%) with other malignancies. The average
operative time was 28+/-8 minutes, and the duration of chest tube drainage was
9.4+/-4.1 days. Side-effects were mild (temporary pain, fever for 2-3 days),
affecting only three (12%) patients. Two patients (8%) died during
hospitalization, due to progression of disease. Overall, pre- and postoperative
Karnofsky performance index (KI) and Medical Research Council (MRC) dyspnea score
were 62.1+/-12.2 vs. 71.3+/-13.2 (p=0.014), and 4.2+/-0.8 vs. 2.7+/-1.0
(p<0.001), respectively. A significant relationship between total amount of
preoperative pleural effusion and both KI (R=-0.54, p=0.002) and MRC (R=0.64,
p=0.0001) was found. No correlation (p=NS, log-rank test) was found between
preoperative KI or MRC and underlying malignancy related to MPE. In conclusion,
thoracoscopic large-particle talc pleurodesis is a feasible and effective
treatment for MPE, significantly improving quality of life of patients.
PMID- 23155298
TI - The Nature-Nurture Debate is Over, and Both Sides Lost! Implications for
Understanding Gender Differences in Religiosity.
PMID- 23155299
TI - Early Patterns of Self-Regulation as Risk and Promotive Factors in Development: A
Longitudinal Study from Childhood to Adulthood in a High-Risk Sample.
AB - The present study examines two childhood markers of self-regulation, ego-control
and ego-resiliency, as promotive factors for the development of global adjustment
and as risk factors for the development of internalizing and externalizing
behavior problems in a high-risk sample. Teachers and observers rated ego-control
and ego-resiliency when participants (n = 136) were in preschool and elementary
school. Ratings showed evidence for convergent and discriminant validity and
stability over time. Ego-resiliency, but not ego-control, emerged as powerful
predictor of adaptive functioning at age 19 and 26, as well as internalizing and
externalizing problems at 16, 23, 26, and 32 years. We interpret these findings
as evidence that flexibility and adaptability -measured with ego-resiliency- may
reduce risk and promote successful adaptation in low-SES environments.
PMID- 23155300
TI - Religiosity, Values, and Acculturation: A Study of Turkish, Turkish Belgian, and
Belgian Adolescents.
AB - We address the understudied religious dimension of acculturation in acculturating
adolescents who combine a religious Islamic heritage with a secularized Christian
mainstream culture. The religiosity of 197 Turkish Belgian adolescents was
compared with that of 366 agemates in Turkey (the heritage culture) and 203 in
Belgium (the mainstream culture) and related to cultural values, acculturation
orientations, and ethnic identification. Belgian adolescents showed lower and
declining religiosity with age, whereas Turkish and Turkish Belgian adolescents
were more religious regardless of age. Acculturating adolescents reaffirmed
religion as compared with monocultural adolescents in Turkey. Religious
reaffirmation was related to cultural values of interdependence, heritage culture
maintenance, and ethnic identification.
PMID- 23155301
TI - Marital Status, Gender, and Home-to-Job Conflict Among Employed Parents.
AB - Although researchers argue that single parents perceive more work-family conflict
than married parents, little research has examined nuances in such differences.
Using data from the 2002 National Study of Changing Workforce (N = 1,430), this
study examines differences in home-to-job conflict by marital status and gender
among employed parents. Findings indicate that single mothers feel more home-to
job conflict than single fathers, married mothers, and married fathers. Some
predictors of home-to-job conflict vary by marital status and gender. Job
pressure is related to home-to-job conflict more for single parents than for
married parents. Age of children is related to conflict for single fathers only.
Whereas an unsupportive workplace culture is related to conflict, especially for
married fathers, the lack of spouses' share of domestic responsibilities is
related to conflict, especially for married mothers. These findings indicate that
marital status and gender create distinct contexts that shape employed parents'
perceived home-to-job conflict.
PMID- 23155302
TI - Global Self-Esteem, Appearance Satisfaction, and Self-Reported Dieting in Early
Adolescence.
AB - Global self-esteem, appearance satisfaction, and self-reported dieting are
interrelated. In the current study, we examine the temporal ordering of global
self-esteem and appearance satisfaction across the early adolescence transition,
from age 10 to age 14, as well as the independent associations of self-esteem and
appearance satisfaction on self-reported dieting at age 14. Participants were 130
firstborn European American adolescents (40% girls). Adolescents who were less
satisfied with their appearance at age 10 reported declines in self-esteem from
age 10 to age 14. Adolescents with lower global self-esteem at age 10 did not
decline in appearance satisfaction. Girls, adolescents with higher BMI scores at
age 10, and adolescents who were less satisfied with their appearance at age 14
all reported more frequent dieting at age 14. Implications for etiological and
intervention models of eating problems in adolescence are considered.
PMID- 23155303
TI - The role of marijuana use etiquette in avoiding targeted police enforcement.
AB - Internationally, where marijuana is illegal, users follow etiquette rules that
prevent negative consequences of use. In this study, adherence to etiquette is
hypothesized to reduce likelihood of marijuana-related police stop/search and
arrest. Ethnographers administered group surveys to a diverse, purposive sample
of 462 marijuana-using peer groups in several areas of New York City. Findings
indicated that lack of etiquette was associated with dramatically higher
likelihood of police stop/search or arrest only for users who were Black, male,
and/or recruited from Harlem/South Bronx. If these users followed a few
identified etiquette rules, their risk of police stop/search or arrest was
comparable to that of other users. Implications are that etiquette represents an
intentional conscientiousness about marijuana use. Groups that are specially
targeted for anti-marijuana enforcement can remediate that heightened risk by
following marijuana etiquette.
PMID- 23155304
TI - Enhanced recovery programme in colorectal surgery: does one size fit all?
AB - Enhanced recovery after surgery (ERAS) employs a multimodal perioperative care
pathway with the aim of attenuating the stress response to surgery and
accelerating recovery. It has been difficult to determine the relative importance
of some of the individual components of these pathways such as epidural analgesia
and laparoscopic colorectal surgery. Some argue that only a rigid adherence to
the published ERAS protocol can achieve the proposed benefits of fast-track
surgery. In this article, we explore some of the areas where the evidence base
may be changing and ask whether a more flexible and individualised approach
should be considered.
PMID- 23155305
TI - Role of Smad7 in inflammatory bowel diseases.
AB - Crohn's disease and ulcerative colitis, the major forms of inflammatory bowel
diseases (IBD) in man, are complex diseases in which genetic and environmental
factors interact to promote an excessive mucosal immune response directed against
normal components of the bacterial microflora. There is also evidence that the
pathologic process is due to defects in counter-regulatory mechanisms, such as
those involving the immunosuppressive cytokine transforming growth factor (TGF)
beta1. Indeed, studies in human IBD tissues and murine models of colitis have
documented a disruption of TGF-beta1 signalling marked by a block in the
phosphorylation of Smad3, a signalling molecule associated with the activated TGF
beta receptor, due to up-regulation of Smad7, an intracellular inhibitor of Smad3
phosphorylation. Knock-down of Smad7 with a specific antisense oligonucleotide
restores TGF-beta1/Smad3 signalling, thus resulting in a marked suppression of
inflammatory cytokine production and attenuation of murine colitis. These
findings together with the demonstration that Smad7 antisense oligonucleotide is
not toxic when administered in mice have paved the way for the development of a
Smad7 antisense oligonucleotide-based pharmaceutical compound that is now ready
to enter the clinics. In this article we review the available data supporting the
pathogenic role of Smad7 in IBD and discuss whether and how Smad7 antisense
therapy could help dampen the ongoing inflammation in IBD.
PMID- 23155306
TI - Levofloxacin/amoxicillin-based schemes vs quadruple therapy for Helicobacter
pylori eradication in second-line.
AB - Worldwide prevalence of Helicobacter pylori (H. pylori) infection is
approximately 50%, with the highest being in developing countries. We compared
cure rates and tolerability (SE) of second-line anti-H. pylori
levofloxacin/amoxicillin (LA)-based triple regimens vs standard quadruple therapy
(QT). An English language literature search was performed up to October 2010. A
meta-analysis was performed including randomized clinical trials comparing 7- or
10-d LA with 7-d QT. In total, 10 articles and four abstracts were identified.
Overall eradication rate in LA was 76.5% (95% CI: 64.4%-97.6%). When only 7-d
regimens were included, cure rate was 70.6% (95% CI: 40.2%-99.1%), whereas for 10
d combinations, cure rate was significantly higher (88.7%; 95% CI: 56.1%-109.9%;
P < 0.05). Main eradication rate for QT was 67.4% (95% CI: 49.7%-67.9%). The 7-d
LA and QT showed comparable efficacy [odds ratio (OR): 1.09; 95% CI: 0.63-1.87],
whereas the 10-d LA regimen was significantly more effective than QT (OR: 5.05;
95% CI: 2.74-9.31; P < 0.001; I(2) = 75%). No differences were reported in QT
eradication rates among Asian and European studies, whereas LA regimens were more
effective in European populations (78.3% vs 67.7%; P = 0.05). Incidence of SE was
lower in LA therapy than QT (OR: 0.39; 95% CI: 0.18-0.85; P = 0.02). A higher
rate of side effects was reported in Asian patients who received QT. Our findings
support the use of 10-d LA as a simple second-line treatment for H. pylori
eradication with an excellent eradication rate and tolerability. The optimal
second-line alternative scheme might differ among countries depending on
quinolone resistance.
PMID- 23155307
TI - Multimodality approach for locally advanced esophageal cancer.
AB - Carcinoma of the esophagus is an aggressive and lethal malignancy with an
increasing incidence worldwide. Incidence rates vary internationally, with the
highest rates found in Southern and Eastern Africa and Eastern Asia, and the
lowest in Western and Middle Africa and Central America. Patients with locally
advanced disease face a poor prognosis, with 5-year survival rates ranging from
15%-34%. Recent clinical trials have evaluated different strategies for
management of locoregional cancer; however, because of stage migration and
changes in disease epidemiology, applying these trials to clinical practice has
become a daunting task. We searched Medline and conference abstracts for
randomized studies published in the last 3 decades. We restricted our search to
articles published in English. Neoadjuvant chemoradiotherapy followed by surgical
resection is an accepted standard of care in the United States. Esophagectomy
remains an essential component of treatment and can lead to improved overall
survival, especially when performed at high volume institutions. The role of
adjuvant chemotherapy following curative resection is still unclear. External
beam radiation therapy alone is considered palliative and is typically reserved
for patients with a poor performance status.
PMID- 23155308
TI - Regulatory T cells in inflammatory bowel diseases and colorectal cancer.
AB - Regulatory T cells (T(regs)) are key elements in immunological self-tolerance.
The number of T(regs) may alter in both peripheral blood and in colonic mucosa
during pathological circumstances. The local cellular, microbiological and
cytokine milieu affect immunophenotype and function of T(regs). Forkhead box P3+
T(regs) function shows altered properties in inflammatory bowel diseases (IBDs).
This alteration of T(regs) function can furthermore be observed between Crohn's
disease and ulcerative colitis, which may have both clinical and therapeutical
consequences. Chronic mucosal inflammation may also influence T(regs) function,
which together with the intestinal bacterial flora seem to have a supporting role
in colitis-associated colorectal carcinogenesis. T(regs) have a crucial role in
the immunoevasion of cancer cells in sporadic colorectal cancer. Furthermore,
their number and phenotype correlate closely with the clinical outcome of the
disease, even if their contribution to carcinogenesis has previously been
controversial. Despite knowledge of the clinical relationship between IBD and
colitis-associated colon cancer, and the growing number of immunological aspects
encompassing sporadic colorectal carcinogenesis, the molecular and cellular links
amongst T(regs), regulation of the inflammation, and cancer development are still
not well understood. In this paper, we aimed to review the current data
surrounding the role of T(regs) in the pathogenesis of IBD, colitis-associated
colon cancer and sporadic colorectal cancer.
PMID- 23155309
TI - Incidence of port-site metastasis after undergoing robotic surgery for biliary
malignancies.
AB - AIM: To investigate the incidence of clinically detected port-site metastasis
(PSM) in patients who underwent robotic surgery for biliary malignancies.
METHODS: Using a prospective database, the patients undergoing fully robotic
surgery for biliary malignancies between January 2009 and January 2011 were
included. Records of patients with confirmed malignancy were reviewed for
clinicopathological data and information about PSM. RESULTS: Sixty-four patients
with biliary tract cancers underwent robotic surgery, and sixty patients met the
inclusion criteria. The median age was 67 year (range: 40-85 year). During a
median 15-mo follow-up period, two female patients were detected solitary PSM
after robotic surgery. The incidence of PSM was 3.3%. Patient 1 underwent robotic
anatomatic left hemihepatectomy and extraction of biliary tumor thrombi for an
Klatskin tumor. She had a subcutaneous mass located at the right lateral
abdominal wall near a trocar scar. Patient 2 underwent robotic
pancreaticoduodenectomy for distal biliary cancer. She had two metachronous
subcutaneous mass situated at the right lateral abdominal wall under a same
trocar scar at 7 and 26 mo. The pathology of the excised PSM masses confirmed
metastatic biliary adenocarcinoma. CONCLUSION: The incidence of PSMs after
robotic surgery for biliary malignancies is relatively low, and biliary cancer
can be an indication of robotic surgery.
PMID- 23155310
TI - Traditional Chinese surgical treatment for anal fistulae with secondary tracks
and abscess.
AB - AIM: To evaluate the efficacy and safety of traditional Chinese surgical
treatment for anal fistulae with secondary tracks and abscess. METHODS: Sixty
patients with intersphincteric or transsphincteric anal fistulas with secondary
tracks and abscess were randomly divided into study group [suture dragging
combined with pad compression (SDPC)] and control group [fistulotomy (FSLT)]. In
the SDPC group, the internal opening was excised and incisions at external
openings were made for drainage. Silk sutures were put through every two
incisions and knotted in loose state. The suture dragging process started from
the first day after surgery and the pad compression process started when all
sutures were removed as wound tissue became fresh and without discharge. In the
FSLT group, the internal opening and all tracts were laid open and cleaned by
normal saline postoperatively till all wounds healed. The time of healing,
postoperative pain score (visual analogue scale), recurrence rate, patient
satisfaction, incontinence evaluation and anorectal manometry before and after
the treatment were examined. RESULTS: There were no significant differences
between the two groups regarding age, gender and fistulae type. The time of
healing was significantly shorter (24.33 d in SDPC vs 31.57 d in FSLT, P < 0.01)
and the patient satisfaction score at 1 mo postoperative follow-up was
significantly higher in the SDPC group (4.07 in SDPC vs 3.37 in FSLT, P < 0.05).
The mean maximal postoperative pain scores were 5.83 +/- 2.5 in SDPC vs 6.37 +/-
2.33 in FSLT and the recurrence rates were 3.33 in SDPC vs 0 in FSLT. None of the
patients in the two groups experienced liquid and solid fecal incontinence and
lifestyle alteration postoperatively. The Wexner score after treatment of
intersphincter fistulae were 0.17 +/- 0.41 in SDPC vs 0.40 +/- 0.89 in FSLT and
trans-sphincter fistulae were 0.13 +/- 0.45 in SDPC vs 0.56 +/- 1.35 in FSLT. The
maximal squeeze pressure and resting pressure declined after treatment in both
groups. The maximal anal squeeze pressures after treatment were reduced (23.17 +/
3.73 Kpa in SDPC vs 22.74 +/- 4.47 Kpa in FSLT) and so did the resting pressures
(12.36 +/- 2.15 Kpa in SDPC vs 11.71 +/- 1.87 Kpa in FSLT), but there were
neither significant differences between the two groups and nor significant
differences before or after treatment. CONCLUSION: Traditional Chinese surgical
treatment SDPC for anal fistulae with secondary tracks and abscess is safe,
effective and less invasive.
PMID- 23155311
TI - Ethyl pyruvate protects against experimental acute-on-chronic liver failure in
rats.
AB - AIM: To investigate the protective effects of ethyl pyruvate (EP) on acute-on
chronic liver failure (ACLF) in rats. METHODS: An ACLF model was established in
rats, and animals were randomly divided into normal, model and EP treatment
groups. The rats in EP treatment group received EP (40 mg/kg) at 3 h, 6 h, 12 h
and 24 h after induction of ACLF. Serum endotoxin, high mobility group box-1
(HMGB1), alanine transaminase (ALT), tumor necrosis factor-alpha (TNF-alpha),
interferon-alpha (IFN-gamma), interleukin (IL)-10 and IL-18 levels, changes of
liver histology and HMGB1 expressions in liver tissues were detected at 48 h
after induction of ACLF. The effects of EP on the survival of ACLF rats were also
observed. RESULTS: Serum levels of endotoxin (0.394 +/- 0.066 EU/mL vs 0.086 +/-
0.017 EU/mL, P < 0.001), HMGB1 (35.42 +/- 10.86 MUg/L vs 2.14 +/- 0.27 MUg/L, P <
0.001), ALT (8415.87 +/- 3567.54 IU/L vs 38.64 +/- 8.82 IU/L, P < 0.001), TNF
alpha (190.77 +/- 12.34 ng/L vs 124.40 +/- 4.12 ng/L, P < 0.001), IFN-gamma
(715.38 +/- 86.03 ng/L vs 398.66 +/- 32.91 ng/L, P < 0.001), IL-10 (6.85 +/- 0.64
ng/L vs 3.49 +/- 0.24 ng/L, P < 0.001) and IL-18 (85.19 +/- 3.49 ng/L vs 55.38 +/
1.25 ng/L, P < 0.001) were significantly increased, and liver tissues presented
severe pathological injury in the model group compared with the normal group.
However, EP administration significantly improved hepatic histopathology and
reduced the serum levels of endotoxin (0.155 +/- 0.045 EU/mL vs 0.394 +/- 0.066
EU/mL, P < 0.001) and inflammatory cytokines (11.13 +/- 2.58 MUg/L vs 35.42 +/-
10.86 MUg/L for HMGB1, 3512.86 +/- 972.67 IU/L vs 8415.87 +/- 3567.54 IU/L for
ALT, 128.55 +/- 5.76 ng/L vs 190.77 +/- 12.34 ng/L for TNF-alpha, 438.16 +/-
38.10 ng/L vs 715.38 +/- 86.03 ng/L for IFN-gamma, 3.55 +/- 0.36 ng/L vs 6.85 +/-
0.64 ng/L for IL-10, and 60.35 +/- 1.63 ng/L vs 85.19 +/- 3.49 ng/L for IL-18,
respectively, P < 0.001), and the levels of HMGB1 in liver tissues regardless of
treatment time after induction of ACLF. EP treatment at the four time points
prolonged the median survival time of ACLF rats (60 h) to 162 h, 120 h, 102 h and
78 h, respectively (chi(2) = 41.17, P < 0.0001). CONCLUSION: EP administration
can protect against ACLF in rats, and is a potential and novel therapeutic agent
for severe liver injury.
PMID- 23155312
TI - Exogenous carbon monoxide attenuates inflammatory responses in the small
intestine of septic mice.
AB - AIM: To determine whether the carbon monoxide (CO)-releasing molecules (CORM)
liberated CO suppress inflammatory responses in the small intestine of septic
mice. METHODS: The C57BL/6 mice (male, n = 36; weight 20 +/- 2 g) were assigned
to four groups in three respective experiments. Sepsis in mice was induced by
cecal ligation and puncture (CLP) (24 h). Tricarbonyldichlororuthenium (II) dimer
(CORM-2) (8 mg/kg, i.v.) was administrated immediately after induction of CLP.
The levels of inflammatory cytokines [interleukin-1beta (IL-1beta) and tumor
necrosis factor-alpha (TNF-alpha)] in tissue homogenates were measured with
enzyme-linked immunosorbent assay. The levels of malondialdehyde (MDA) in the
tissues were determined. The levels of nitric oxide (NO) in tissue homogenate
were measured and the expression levels of intercellular adhesion molecule 1
(ICAM-1) and inducible nitric oxide synthase (iNOS) in the small intestine were
also assessed. NO and IL-8 levels in the supernatants were determined after the
human adenocarcinoma cell line Caco-2 was stimulated by lipopolysaccharide (LPS)
(10 g/mL) for 4 h in vitro. RESULTS: At 24 h after CLP, histological analysis
showed that the ileum and jejunum from CLP mice induced severe edema and
sloughing of the villous tips, as well as infiltration of inflammatory cells into
the mucosa. Semi-quantitative analysis of histological samples of ileum and
jejunum showed that granulocyte infiltration in the septic mice was significantly
increased compared to that in the sham group. Administration of CORM-2
significantly decreased granulocyte infiltration. At 24 h after CLP, the tissue
MDA levels in the mid-ileum and mid-jejunum significantly increased compared to
the sham animals (103.68 +/- 23.88 nmol/mL vs 39.66 +/- 8.23 nmol/mL, 89.66 +/-
9.98 nmol/mL vs 32.32 +/- 7.43 nmol/mL, P < 0.01). In vitro administration of
CORM-2, tissue MDA levels were significantly decreased (50.65 +/- 11.46 nmol/mL,
59.32 +/- 6.62 nmol/mL, P < 0.05). Meanwhile, the tissue IL-1beta and TNF-alpha
levels in the mid-ileum significantly increased compared to the sham animals
(6.66 +/- 1.09 pg/mL vs 1.67 +/- 0.45 pg/mL, 19.34 +/- 3.99 pg/mL vs 3.98 +/-
0.87 pg/mL, P < 0.01). In vitro administration of CORM-2, tissue IL-1beta and TNF
alpha levels were significantly decreased (3.87 +/- 1.08 pg/mL, 10.45 +/- 2.48
pg/mL, P < 0.05). The levels of NO in mid-ileum and mid-jejunum tissue homogenate
were also decreased (14.69 +/- 2.45 nmol/mL vs 24.36 +/- 2.97 nmol/mL, 18.47 +/-
2.47 nmol/mL vs 27.33 +/- 3.87 nmol/mL, P < 0.05). The expression of iNOS and
ICAM-1 in the mid-ileum of septic mice at 24 h after CLP induction significantly
increased compared to the sham animals. In vitro administration of CORM-2,
expression of iNOS and ICAM-1 were significantly decreased. In parallel, the
levels of NO and IL-8 in the supernatants of Caco-2 stimulated by LPS was
markedly decreased in CORM-2-treated Caco-2 cells (2.22 +/- 0.12 nmol/mL vs 6.25
+/- 1.69 nmol/mL, 24.97 +/- 3.01 pg/mL vs 49.45 +/- 5.11 pg/mL, P < 0.05).
CONCLUSION: CORM-released CO attenuates the inflammatory cytokine production (IL
1beta and TNF-alpha), and suppress the oxidative stress in the small intestine
during sepsis by interfering with protein expression of ICAM-1 and iNOS.
PMID- 23155313
TI - Intramuscular vs intradermal route for hepatitis B booster vaccine in celiac
children.
AB - AIM: To compare intradermal (ID) and intramuscular (IM) booster doses, which have
been used in healthy and high risk subjects, such as healthcare workers,
haemodialysis patients, human immunodeficiency virus patients, and renal
transplant recipients unresponsive to initial hepatitis B vaccination, in celiac
individuals. METHODS: We conducted our study on 58 celiac patients, vaccinated in
the first year of life, whose blood analysis had showed the absence of protective
hepatitis B virus (HBV) antibodies. All patients had received the last vaccine
injection at least one year before study enrolment and they had been on a gluten
free diet for at least 1 year. In all patients we randomly performed an HBV
vaccine booster dose by ID or IM route. Thirty celiac patients were revaccinated
with recombinant hepatitis B vaccine (Engerix B) 2 MUg by the ID route, while 28
celiac patients were revaccinated with Engerix B 10 MUg by the IM route. Four
weeks after every booster dose, the anti-hepatitis B surface (HBs) antibody titer
was measured by an enzyme-linked immune-adsorbent assay. We performed a maximum
of three booster doses in patients with no anti-HBs antibodies after the first or
the second vaccine dose. The cut off value for a negative anti-HBs antibody titer
was 10 IU/L. Patients with values between 10 and 100 IU/L were considered "low
responders" while patients with an antibody titer higher than 1000 IU/L were
considered "high responders". RESULTS: No significant difference in age, gender,
duration of illness, and years of gluten intake was found between the two groups.
We found a high percentage of "responders" after the first booster dose (ID =
76.7%, IM = 78.6%) and a greater increase after the third dose (ID = 90%, IM =
96.4%) of vaccine in both groups. Moreover we found a significantly higher number
of high responders (with an anti-HBs antibody titer > 1000 IU/L) in the ID (40%)
than in the IM (7.1%) group, and this difference was evident after the first
booster dose of vaccination (P < 0.01). No side effects were recorded in
performing delivery of the vaccine by either the ID or IM route. CONCLUSION: Our
study suggests that both ID and IM routes are effective and safe options to
administer a booster dose of HBV vaccine in celiac patients. However the ID route
seems to achieve a greater number of high responders and to have a better
cost/benefit ratio.
PMID- 23155314
TI - Prognostic factors for recurrence of gastrointestinal bleeding due to Dieulafoy's
lesion.
AB - AIM: To analyze the effectiveness of the endoscopic therapy and to identify
prognostic factors for recurrent bleeding. METHODS: Retrospective study of
patients with gastrointestinal bleeding secondary to Dieulafoy's lesion (DL) from
2005 to 2011. We analyzed the demographic characteristics of the patients, risk
factors for gastrointestinal bleeding, endoscopic findings, characteristics of
the endoscopic treatment, and the recurrence of bleeding. We included cases in
which endoscopy described a lesion compatible with Dieulafoy. We excluded
patients who had potentially bleeding lesions such as angiodysplasia in other
areas or had undergone other gastrointestinal endoscopic procedures. RESULTS:
Twenty-nine patients with DL were identified. Most of them were men with an
average age of 71.5 years. Fifty-five percent of the patients received
antiaggregatory or anticoagulant therapy. The most common location for DL was the
stomach (51.7%). The main type of bleeding was oozing in 65.5% of cases. In 27.6%
of cases, there was arterial (spurting) bleeding, and 6.9% of the patients
presented with an adherent clot. A single endoscopic treatment was applied to
nine patients (31%); eight of them with adrenaline and one with argon, while 69%
of the patients received combined treatment. Six patients (20.7%) presented with
recurrent bleeding at a median of 4 d after endoscopy (interquartile range =
97.75). Within these six patients, the new endoscopic treatment obtained a
therapeutic success of 100%. The presence of arterial bleeding at endoscopy was
associated with a higher recurrence rate for bleeding (50% vs 33.3% for other
type of bleeding) [P = 0.024, odds ratio (OR) = 8.5, 95% CI = 1.13-63.87]. The
use of combined endoscopic treatment prevented the recurrence of bleeding (10% vs
44.4% of single treatment) (P = 0.034, OR = 0.14, 95% CI = 0.19-0.99).
CONCLUSION: Endoscopic treatment of DL is safe and effective. Adrenaline
monotherapy and arterial (spurting) bleeding are associated with a high rate of
bleeding recurrence.
PMID- 23155315
TI - Incidence of human papilloma virus in esophageal squamous cell carcinoma in
patients from the Lublin region.
AB - AIM: To assess the prevalence of human papilloma virus (HPV) in esophageal
squamous cell carcinoma (ESCC) in the south-eastern region of Poland. METHODS:
The study population consisted of 56 ESCC patients and 35 controls. The controls
were patients referred to our department due to other non-esophageal and non
oncological disorders with no gross or microscopic esophageal pathology as
confirmed by endoscopy and histopathology. In the ESCC patients, samples were
taken from normal mucosa (56 mucosa samples) and from the tumor (56 tumor
samples). Tissue samples from the controls were taken from normal mucosa of the
middle esophagus (35 control samples). Quantitative determination of DNA was
carried out using a spectrophotometric method. Genomic DNA was isolated using the
QIAamp DNA Midi Kit. HPV infection was identified following PCR amplification of
the HPV gene sequence, using primers MY09 and MY11 complementary to the genome
sequence of at least 33 types of HPV. The sequencing results were computationally
analyzed using the basic local alignment search tool database. RESULTS: In tumor
samples, HPV DNA was identified in 28 of 56 patients (50%). High risk HPV
phenotypes (16 or/and 18) were found in 5 of 56 patients (8.9%), low risk in 19
of 56 patients (33.9%) and other types of HPV (37, 81, 97, CP6108) in 4 of 56
patients (7.1%). In mucosa samples, HPV DNA was isolated in 21 of 56 patients
(37.5%). High risk HPV DNA was confirmed in 3 of 56 patients (5.3%), low risk HPV
DNA in 12 of 56 patients (21.4%), and other types of HPV in 6 of 56 patients
(10.7%). In control samples, HPV DNA was identified in 4 of 35 patients (11.4%)
with no high risk HPV. The occurrence of HPV in ESCC patients was significantly
higher than in the controls [28 of 56 (50%) vs 4 of 35 (11.4%), P < 0.001]. In
esophageal cancer patients, both in tumor and mucosa samples, the predominant HPV
phenotypes were low risk HPV, isolated 4 times more frequently than high risk
phenotypes [19 of 56 (33.9%) vs 5 of 56 (8.9%), P < 0.001]. A higher prevalence
of HPV was identified in female patients (71.4% vs 46.9%). Accordingly, the high
risk phenotypes were isolated more frequently in female patients and this
difference reached statistical significance [3 of 7 (42.9%) vs 2 of 49 (4.1%), P
< 0.05]. Of the pathological characteristics, only an infiltrative pattern of
macroscopic tumor type significantly correlated with the presence of HPV DNA in
ESCC samples [20 of 27 (74.1%) vs 8 of 29 (27.6%) for ulcerative or protruding
macroscopic type, P < 0.05]. The occurrence of total HPV DNA and both HPV high or
low risk phenotypes did not significantly differ with regard to particular grades
of cellular differentiation, phases in depth of tumor infiltration, grades of
nodal involvement and stages of tumor progression. CONCLUSION: Low risk HPV
phenotypes could be one of the co-activators or/and co-carcinogens in complex,
progressive, multifactorial and multistep esophageal carcinogenesis.
PMID- 23155316
TI - Intussusception due to inflammatory fibroid polyp: a case report and
comprehensive literature review.
AB - AIM: To give an overview of the literature on intussusception due to inflammatory
fibroid polyp (IFP). METHODS: We present a new case of ileal intussusception due
to IFP and a literature review of studies published in English language on
intussusception due to IFP, accessed via PubMed and Google Scholar databases. For
the search, the keywords used were: intussusception, IFP, intussusception and
IFP, intussusception due to IFP, and IFP presenting as intussusception. The
search covered all articles from 1976 to November 2011. RESULTS: We present a 38
year-old woman who was admitted 10 d after experiencing abdominal pain, vomiting,
and nausea. Ultrasonography demonstrated small bowel intussusception. An ileal
intussusception due to a mass lesion 50 cm proximal to the ileocecal junction was
found during laparotomy. Partial ileal resection and anastomosis were performed.
A diagnosis of ileal IFP was made based on the immunohistochemical findings. In
addition, a total of 56 reports concerning 85 cases of intussusception due to IFP
meeting the aforementioned criteria was included in the literature review. The
patients were aged 4 to 81 years (mean, 49 +/- 16.2 years); 44 were women (mean,
51.8 +/- 14.3 years) and 41 were men (mean, 46 +/- 17.5 years). According to the
location of the IFP, ileal intussusception was found in 63 patients, while 17 had
jejunal, three had colonic, and two had ileojejunal intussusception. CONCLUSION:
Although IFPs are rare and benign, surgery is the only solution in case of
intestinal obstruction. Differential diagnosis should be made via
immunohistochemical examination.
PMID- 23155317
TI - Evaluation of sorafenib for hepatocellular carcinoma by contrast-enhanced
ultrasonography: a pilot study.
AB - AIM: To determine the usefulness of arrival time parametric imaging (AtPI) using
contrast-enhanced ultrasonography (CEUS) with Sonazoid in evaluating early
response to sorafenib for hepatocellular carcinoma (HCC). METHODS: Fourteen
advanced HCC patients who received sorafenib 400/800 mg/d for at least 4 wk and
were followed up by CEUS were enrolled in this study. CEUS was performed before
treatment and 2 and 4 wk after treatment, and images of the target lesion in the
arterial phase were recorded for each patient. The images were analyzed by AtPI.
Color mapping (CM) images obtained by AtPI were compared before and after the
treatment. In these CM images, the mean arrival time of the contrast agent in the
region of interest from the starting point [mean time (MT)] was calculated. In
each patient, differences between MT before and MT 2 and 4 wk after the treatment
were compared with responses evaluated 4-8 wk after the treatment by dynamic
computed tomography (CT), and statistical analysis was performed. Modified
response evaluation criteria in solid tumors was used for the response
evaluation. RESULTS: In CM images both 2 and 4 wk after the treatment, delays in
the arrival time of the contrast agent were noted in 8 of the 14 patients. In the
other 6 patients, no color changes were observed in the tumor, or red and/or
yellow increase, suggesting a decrease in blood flow velocity between images 2
and 4 wk after the treatment and those before the treatment. Dynamic CT could be
performed 4-8 wk after the treatment in 13 of the 14 patients. Median differences
in the MT were 1.13 s and 1.015 s, 2 and 4 wk after the treatment, respectively,
in the 8 patients who showed stable disease (SD)/partial response (PR) on dynamic
CT. Median differences in the MT were -0.39 s and -0.95 s, 2 and 4 wk after the
treatment, respectively, in the 5 patients who showed progressive disease (PD).
Differences in the median MT between SD/PR and PD groups were significant 2 and 4
wk after the treatment with P = 0.019 and P = 0.028, respectively. CONCLUSION:
AtPI by CEUS using Sonazoid is suggested to be useful for evaluating early
responses to sorafenib.
PMID- 23155318
TI - Nutritional status in relation to lifestyle in patients with compensated viral
cirrhosis.
AB - AIM: To assess the nourishment status and lifestyle of non-hospitalized patients
with compensated cirrhosis by using noninvasive methods. METHODS: The subjects
for this study consisted of 27 healthy volunteers, 59 patients with chronic viral
hepatitis, and 74 patients with viral cirrhosis, from urban areas. We assessed
the biochemical blood tests, anthropometric parameters, diet, lifestyle and
physical activity of the patients. A homeostasis model assessment-insulin
resistance (HOMA-IR) value of >= 2.5 was considered to indicate insulin
resistance. We measured height, weight, waist circumference, arm circumference,
triceps skin-fold thickness, and handgrip strength, and calculated body mass
index, arm muscle circumference (AMC), and arm muscle area (AMA). We interviewed
the subjects about their dietary habits and lifestyle using health assessment
computer software. We surveyed daily physical activity using a pedometer.
Univariate and multivariate logistic regression modeling were used to identify
the relevant factors for insulin resistance. RESULTS: The rate of patients with
HOMA-IR >= 2.5 (which was considered to indicate insulin resistance) was 14
(35.9%) in the chronic hepatitis and 17 (37.8%) in the cirrhotic patients. AMC
(%) (control vs chronic hepatitis, 111.9% +/- 10.5% vs 104.9% +/- 10.7%, P =
0.021; control vs cirrhosis, 111.9% +/- 10.5% vs 102.7% +/- 10.8%, P = 0.001) and
AMA (%) (control vs chronic hepatitis, 128.2% +/- 25.1% vs 112.2% +/- 22.9%, P =
0.013; control vs cirrhosis, 128.2% +/- 25.1% vs 107.5% +/- 22.5%, P = 0.001) in
patients with chronic hepatitis and liver cirrhosis were significantly lower than
in the control subjects. Handgrip strength (%) in the cirrhosis group was
significantly lower than in the controls (control vs cirrhosis, 92.1% +/- 16.2%
vs 66.9% +/- 17.6%, P < 0.001). The results might reflect a decrease in muscle
mass. The total nutrition intake and amounts of carbohydrates, protein and fat
were not significantly different amongst the groups. Physical activity levels
(kcal/d) (control vs cirrhosis, 210 +/- 113 kcal/d vs 125 +/- 74 kcal/d, P =
0.001), number of steps (step/d) (control vs cirrhosis, 8070 +/- 3027 step/d vs
5789 +/- 3368 step/d, P = 0.011), and exercise (Ex) (Ex/wk) (control vs
cirrhosis, 12.4 +/- 9.3 Ex/wk vs 7.0 +/- 7.7 Ex/wk, P = 0.013) in the cirrhosis
group was significantly lower than the control group. The results indicate that
the physical activity level of the chronic hepatitis and cirrhosis groups were
low. Univariate and multivariate logistic regression modeling suggested that Ex
was associated with insulin resistance (odds ratio, 6.809; 95% CI, 1.288-36.001;
P = 0.024). The results seem to point towards decreased physical activity being a
relevant factor for insulin resistance. CONCLUSION: Non-hospitalized cirrhotic
patients may need to maintain an adequate dietary intake and receive lifestyle
guidance to increase their physical activity levels.
PMID- 23155319
TI - Correlations between endoscopic and clinical disease activity indices in
intestinal Behcet's disease.
AB - AIM: To develop a novel endoscopic severity model of intestinal Behcet's disease
(BD) and to evaluate its feasibility by comparing it with the actual disease
activity index for intestinal Behcet's disease (DAIBD). METHODS: We reviewed the
medical records of 167 intestinal BD patients between March 1986 and April 2011.
We also investigated the endoscopic parameters including ulcer locations,
distribution, number, depth, shape, size and margin to identify independent
factors associated with DAIBD. An endoscopic severity model was developed using
significant colonoscopic variables identified by multivariate regression analysis
and its correlation with the DAIBD was evaluated. To determine factors related to
the discrepancy between endoscopic severity and clinical activity, clinical
characteristics and laboratory markers of the patients were analyzed. RESULTS: A
multivariate regression analysis revealed that the number of intestinal ulcers
(>= 2, P = 0.031) and volcanoshaped ulcers (P = 0.001) were predictive factors
for the DAIBD. An endoscopic severity model (Y) was developed based on selected
endoscopic variables as follows: Y = 47.44 + 9.04 * non-Ileocecal area + 11.85 *
>= 2 of intestinal ulcers + 5.03 * shallow ulcers + 12.76 * deep ulcers + 4.47 *
geographic-shaped ulcers + 26.93 * volcano-shaped ulcers + 8.65 * >= 20 mm of
intestinal ulcers. However, endoscopic parameters used in the multivariate
analysis explained only 18.9% of the DAIBD variance. Patients with severe DAIBD
scores but with moderately predicted disease activity by the endoscopic severity
model had more symptoms of irritable bowel syndrome (21.4% vs 4.9%, P = 0.026)
and a lower rate of corticosteroid use (50.0% vs 75.6%, P = 0.016) than those
with severe DAIBD scores and accurately predicted disease by the model.
CONCLUSION: Our study showed that the number of intestinal ulcers and volcano
shaped ulcers were predictive factors for severe DAIBD scores. However, the
correlation between endoscopic severity and DAIBD (r = 0.434) was weak.
PMID- 23155320
TI - Bisphosphonate use and gastrointestinal tract cancer risk: meta-analysis of
observational studies.
AB - AIM: To perform a meta-analysis of observational studies to further elucidate the
relationship between oral bisphosphonate use and gastrointestinal cancer risk.
METHODS: Systematic literature search was conducted in MEDLINE, EMBASE, and the
Cochrane Library to identify studies through January 2011. Search terms were
"bisphosphonates" or trade names of the drugs, and "observational studies" or
"cohort studies" or "case-control studies". Two evaluators reviewed and selected
articles on the basis of predetermined selection criteria as followed: (1)
observational studies (case-control or cohort studies) on bisphosphonate use; (2)
with at least 2 years of follow-up; and (3) reported data on the incidence of
cancer diagnosis. The DerSimonian and Laird random effects model were used to
calculate the pooled relative risk (RR) with 95% confidence interval (CI). Two-by
two contingency table was used to calculate the outcomes not suitable for meta
analysis. Subgroup meta-analyses were conducted for the type of cancer
(esophageal, gastric and colorectal cancers). Sensitivity analyses were performed
to examine the effect sizes when only studies with long-term follow-up (mean 5
years; subgroup 3 years) were included. RESULTS: Of 740 screened articles, 3
cohort studies and 3 case-control studies were included in the analyses. At
first, 4 cohort studies and 3 case-control studies were selected for the analyses
but one cohort study was excluded because the cancer outcomes were not
categorized by type of gastrointestinal cancer. More than 124,686 subjects
participated in the 3 cohort studies. The mean follow-up time in all of the
cohort studies combined was approximately 3.88 years. The 3 case-control studies
reported 3070 esophageal cancer cases and 15,417 controls, 2018 gastric cancer
cases and 10,007 controls, and 11,574 colorectal cancer cases and 53,955
controls. The percentage of study participants who used bisphosphonate was 2.8%
among the cases and 2.9% among the controls. The meta-analysis of all the studies
found no significant association between bisphosphonate use and gastrointestinal
cancer. Also no statistically significant association was found in a meta
analysis of long-term follow-up studies. There was no negative association
between bisphosphonate use and the incidence of esophageal cancer in the overall
analysis (RR 0.96, 95% CI: 0.65-1.42, I(2) = 52.8%, P = 0.076) and no
statistically significant association with long-term follow-up (RR 1.74, 95% CI:
0.97-3.10, I(2) = 58.8%, P = 0.119). No negative association was found in the
studies reporting the risk of gastric cancer (RR 0.89, 95% CI: 0.71-1.13, I(2) =
0.0%, P = 0.472). In case of colorectal cancer, there was no association between
colorectal cancer and bisphosphonate use (RR 0.62, 95% CI: 0.30-1.29, I(2) =
88.0%, P = 0.004) and also in the analysis with long-term follow-up (RR 0.61, 95%
CI: 0.28-1.35, I(2) = 84.6%, P = 0.011). CONCLUSION: Oral bisphosphonate use had
no significant effect on gastrointestinal cancer risk. However, this finding
should be validated in randomized controlled trials with long-term follow-up.
PMID- 23155321
TI - Effect of ezetimibe on the prevalence of cholelithiasis.
AB - AIM: To investigate the prevalence of cholelithiasis among patients treated with
ezetimibe. METHODS: A retrospective, case-control study based on computerized
medical records from patients of the Clalit Health Services, Sharon-Shomron
region, from 2000 to 2009. Patients 20-85 years of age, who had been treated with
ezetimibe and statins or statins only for at least 6 mo, and who had an abdominal
ultrasound were included in the study. Collected data included age, gender,
ezetimibe treatment duration, presence of hypothyroidism or diabetes, and
existence of cholelithiasis as determined by ultrasound. Excluded were subjects
after gallbladder resection, with hemolysis, myeloproliferative or inflammatory
bowel diseases, and those treated with ursodeoxycholic acid and fibrates.
Patients treated with statins and ezetimibe (study group) were compared to
patients treated with statins only (control group). RESULTS: The study group
included 25 patients and the control group 168. All patients in the study were
treated with statins. The study group included 13 males (52%) and 12 females
(48%), the control group 76 males (45%) and 92 (55%) females (P = 0.544). The
groups did not differ in age (mean age: 68 +/- 8 years, range 53-85 years vs mean
age: 71 +/- 8 years, range 51-85 years; P = 0.153) or in the rate of diabetic and
hypothyroid patients [11 (44%) vs 57 (33%), P = 0.347 in the study group and 5
(20%) vs 23 (14%), P = 0.449 in the control group, respectively]. Patients in the
study group were treated with ezetimibe for an average of 798 +/- 379 d.
Cholelithiasis was found in 4 (16%) patients in the study group and in 33 (20%)
patients in the control group (P = 0.666). CONCLUSION: Ezetimibe does not appear
to influence the prevalence of gallstones.
PMID- 23155322
TI - Treatment of chronic hepatitis delta virus with peg-interferon and factors that
predict sustained viral response.
AB - AIM: To observe the efficacy of peg-interferon in the treatment of hepatitis
delta virus (HDV) and to identify the factors that would be predictive of the
sustained viral response (SVR). METHODS: This prospective study was conducted in
Medical Unit IV of the Liaquat University of Medical and Health Sciences Hospital
Jamshoro from June 2008 to September 2011. This study cohort included all
patients of either sex who presented during this time with hepatitis B surface
antigen positivity, hepatitis B virus DNA > 20,000 IU/mL, serum glutamic pyruvic
transaminase (SGPT) > 2(upper limit of normal), HDV-RNA positivity with fibrosis
stage >= 2. Informed consent was obtained from each of these individuals.
Patients were diagnosed with hepatitis D on the basis of detectable viral
antibodies and the presence of HDV-RNA in their serum. A liver biopsy was
performed in all cases and fibrosis staging was performed in accordance with the
METAVIR scoring system. All eligible patients were administered peg-interferon at
a weekly dosage of 1.5 MUg/kg body weight for 48 wk. HDV-RNA was assayed at the
end of this treatment period and again at 24 wk later. A biochemical response was
determined by a normalization of SGPT at the end of the treatment or during
follow up. The end of treatment response was defined by a HDV-RNA negative
status. A sustained virological response was defined by undetectable serum HDV
RNA at six months after the end of treatment. RESULTS: Among the 277 patients
enrolled in our present study, 238 completed a course of peg-interferon therapy
of which 180 (75.6%) were male and 58 (24.4%) female. Biochemical responses were
achieved in 122/238 (51.3%) patients. End of treatment responses were achieved in
71/238 (29.8%) cases. A SVR was achieved in 70 of these patients (29.4%). A
strong association was found between the SVR and the end of treatment responses
(P = 0.001), biochemical responses (P = 0.001) and the degree of fibrosis (P =
0.002). CONCLUSION: Peg-interferon therapy can induce remission in nearly one
third of patients harboring HDV.
PMID- 23155323
TI - Endoscopic submucosal dissection for foregut neuroendocrine tumors: an initial
study.
AB - AIM: To evaluate the feasibility and efficacy of endoscopic submucosal dissection
(ESD) for foregut neuroendocrine tumors (NETs). METHODS: From April 2008 to
December 2010, patients with confirmed histological diagnosis of foregut NETs
were included. None had regional lymph node enlargement or distant metastases to
the liver or lung on preoperative computerized tomography scanning or endoscopic
ultrasonography (EUS). ESD was attempted under general anesthesia. After making
several marking dots around the lesion, a mixture solution was injected into the
submucosa. The mucosa was incised outside the marking dots. Dissection of the
submucosal layer beneath the tumor was performed under direct vision to achieve
complete en bloc resection of the specimen. Tumor features, clinicopathological
characteristics, complete resection rate, and complications were evaluated.
Foregut NETs were graded as G1, G2, or G3 on the basis of proliferative activity
by mitotic count or Ki-67 index. All patients underwent regular follow-up to
evaluate for any local recurrence or distant metastasis. RESULTS: Those treated
by ESD included 24 patients with 29 foregut NETs. The locations of the 29 lesions
are as follows: esophagus (n = 1), cardia (n = 1), stomach (n = 23), and duodenal
bulb (n = 4). All lesions were found incidentally during routine upper
gastrointestinal endoscopy for other indications, and none had symptoms of
carcinoid syndrome. Preoperative EUS showed that all tumors were confined to the
submucosa. Among the 24 gastric lesions, 16 lesions in 11 patients were type I
gastric NETs arising in chronic atrophic gastritis with hypergastrinemia, while
the other 8 solitary lesions were type III because of absence of atrophic
gastritis in these cases. All of the tumors were removed in an en bloc fashion.
The average maximum diameter of the lesions was 9.4 mm (range: 2-30 mm), and the
procedure time was 20.3 min (range: 10-45 min). According to the World Health
Organization 2010 classification, histological evaluation determined that 26
lesions were NET-G1, 2 gastric lesions were NET-G2, and 1 esophageal lesion was
neuroendocrine carcinoma (NEC). Complete resection was achieved in 28 lesions
(28/29, 96.6%), and all of them were confined to the submucosa in histopathologic
assessment with no lymphovascular invasion. The remaining patient with NEC
underwent additional surgery because the resected specimens revealed
angiolymphatic and muscularis invasion, as well as incomplete resection. Delayed
bleeding occurred in 1 case 3 d after ESD, which was managed by endoscopic
treatment. There were no procedure-related perforations. During a mean follow-up
period of 24.4 mo (range: 12-48 mo), local recurrence occurred in only 1 patient
7 mo after initial ESD. This patient successfully underwent repeat ESD.
Metastasis to lymph nodes or distal organs was not observed in any patient. No
patients died during the study period. CONCLUSION: ESD appears to be a safe,
feasible, and effective procedure for providing accurate histopathological
evaluations and curative treatment for eligible foregut NETs.
PMID- 23155324
TI - Anorectal functional outcome after repeated transanal endoscopic microsurgery.
AB - AIM: To evaluate the status of anorectal function after repeated transanal
endoscopic microsurgery (TEM). METHODS: Twenty-one patients undergoing subtotal
colectomy with ileorectal anastomosis were included. There were more than 5 large
(> 1 cm) polyps in the remaining rectum (range: 6-20 cm from the anal edge). All
patients, 19 with villous adenomas and 2 with low-grade adenocarcinomas,
underwent TEM with submucosal endoscopic excision at least twice between 2005 and
2011. Anorectal manometry and a questionnaire about incontinence were carried out
at week 1 before operation, and at weeks 2 and 3 and 6 mo after the last
operation. Anal resting pressure, maximum squeeze pressure, maximum tolerable
volume (MTV) and rectoanal inhibitory reflexes (RAIR) were recorded. The
integrity and thickness of the internal anal sphincter (IAS) and external anal
sphincter (EAS) were also evaluated by endoanal ultrasonography. We determined
the physical and mental health status with SF-36 score to assess the effect of
multiple TEM on patient quality of life (QoL). RESULTS: All patients answered the
questionnaire. Apart from negative RAIR in 4 patients, all of the anorectal
manometric values in the 21 patients were normal before operation. Mean anal
resting pressure decreased from 38 +/- 5 mmHg to 19 +/- 3 mmHg (38 +/- 5 mmHg vs
19 +/- 3 mmHg, P = 0.000) and MTV from 165 +/- 19 mL to 60 +/- 11 mL (165 +/- 19
mL vs 60 +/- 11 mL, P = 0.000) at month 3 after surgery. Anal resting pressure
and MTV were 37 +/- 5 mmHg (38 +/- 5 mmHg vs 37 +/- 5 mmHg, P = 0.057) and 159 +/
19 mL (165 +/- 19 mL vs 159 +/- 19 mL, P = 0.071), respectively, at month 6
after TEM. Maximal squeeze pressure decreased from 171 +/- 19 mmHg to 62 +/- 12
mmHg (171 +/- 19 mmHg vs 62 +/- 12 mmHg, P = 0.000) at week 2 after operation,
and returned to normal values by postoperative month 3 (171 +/- 19 vs 166 +/- 18,
P = 0.051). RAIR were absent in 4 patients preoperatively and in 12 (chi(2) =
4.947, P = 0.026) patients at month 3 after surgery. RAIR was absent only in 5
patients at postoperative month 6 (chi(2) = 0.141, P = 0.707). Endosonography
demonstrated that IAS disruption occurred in 8 patients, and 6 patients had
temporary incontinence to flatus that was normalized by postoperative month 3.
IAS thickness decreased from 1.9 +/- 0.6 mm preoperatively to 1.3 +/- 0.4 mm (1.9
+/- 0.6 mm vs 1.3 +/- 0.4 mm, P = 0.000) at postoperative month 3 and increased
to 1.8 +/- 0.5 mm (1.9 +/- 0.6 mm vs 1.8 +/- 0.5 mm, P = 0.239) at postoperative
month 6. EAS thickness decreased from 3.7 +/- 0.6 mm preoperatively to 3.5 +/-
0.3 mm (3.7 +/- 0.6 mm vs 3.5 +/- 0.3 mm, P = 0.510) at month 3 and then
increased to 3.6 +/- 0.4 mm (3.7 +/- 0.6 mm vs 3.6 +/- 0.4 mm, P = 0.123) at
month 6 after operation. Most patients had frequent stools per day and relatively
high Wexner scores in a short time period. While actual fecal incontinence was
exceptional, episodes of soiling were reported by 3 patients. With regard to the
QoL, the physical and mental health status scores (SF-36) were 56.1 and 46.2 (50
in the general population), respectively. CONCLUSION: The anorectal function
after repeated TEM is preserved. Multiple TEM procedures are useful for resection
of multi-polyps in the remaining rectum.
PMID- 23155325
TI - Treatment of recurrent sigmoid volvulus in Parkinson's disease by percutaneous
endoscopic colostomy.
AB - The exact aetiology of sigmoid volvulus in Parkinson's disease (PD) remains
unclear. A multiplicity of factors may give rise to decreased gastrointestinal
function in PD patients. Early recognition and treatment of constipation in PD
patients may alter complications like sigmoid volvulus. Treatment of sigmoid
volvulus in PD patients does not differ from other patients and involves
endoscopic detorsion. If feasible, secondary sigmoidal resection should be
performed. However, if the expected surgical morbidity and mortality is
unacceptably high or if the patient refuses surgery, percutaneous endoscopic
colostomy (PEC) should be considered. We describe an elderly PD patient who
presented with sigmoid volvulus. She was treated conservatively with endoscopic
detorsion. Surgery was consistently refused by the patient. After recurrence of
the sigmoid volvulus a PEC was placed.
PMID- 23155326
TI - Sarcoidosis and chronic hepatitis C: a case report.
AB - Several case reports deal with the relationship between hepatitis C virus (HCV)
infection and pulmonary or hepatic sarcoidosis. Most publications describe
interferon alpha-induced sarcoidosis. However, HCV infection per se is also
suggested to cause sarcoidosis. The present case report describes a case of
biopsy-verified lung and liver sarcoidosis and HCV infection, and the outcome of
antiviral therapy. In March 2009, a 25-year-old man presented with moderately
elevated liver enzymes without any clinical symptoms. The patient was positive
for HCV antibodies and HCV RNA of genotype 1b. Four months later the patient
became dyspnoic and pulmonary sarcoidosis was diagnosed by lung biopsy and
radiography. A short course of corticosteroid treatment relieved symptoms. Three
months later, liver biopsy showed noncaseating granulomas consisting of
epithelioid histiocytes and giant cells with a small amount of peripheral
lymphocyte infiltration, without any signs of fibrosis. Chronic HCV infection
with coexistence of pulmonary and hepatic sarcoidosis was diagnosed. Antiviral
therapy with peginterferon alpha and ribavirin at standard doses was started,
which lasted 48 wk, and sustained viral response was achieved. A second liver
biopsy showed disappearance of granulomas and chest radiography revealed
normalization of mediastinal and perihilar glands. The hypothesis that HCV
infection per se may have triggered systemic sarcoidosis was proposed. Successful
treatment of HCV infection led to continuous remission of pulmonary and hepatic
sarcoidosis. Further studies are required to understand the relationship between
systemic sarcoidosis and HCV infection.
PMID- 23155327
TI - Different imaging findings of inflammatory myofibroblastic tumor of the liver.
AB - Inflammatory myofibroblastic tumor (IMT) in the liver is an uncommon lesion of
uncertain pathogenesis. In most cases, symptomatological imaging and clinical
studies suggest malignancy. We report a case of liver IMT with imaging findings
from positron emission tomography/computed tomography (PET/CT), contrast-enhanced
computed tomography (CECT) and contrast-enhanced ultrasonography (CEUS). This
report was the first to depict a PET/CT scan of a liver IMT that revealed an
inhomogeneous, intense (fluorine 18)-fluoro-2-deoxy-D-glucose uptake. The CECT
and CEUS images showed a hepatic artery supplying blood to the mass and necrosis.
The characteristic histopathological features and the presence of spindle cells
expressing smooth muscle actin, collagen fibers and lymphocytes allowed for the
diagnosis of liver IMT. Recognizing such findings will help to achieve a correct
diagnosis and may prevent inappropriate treatment.
PMID- 23155328
TI - Midgut volvulus due to jejunal diverticula: a case report.
AB - Jejunal diverticulosis is uncommon and often asymptomatic. It can produce
significant complications, and some complications are potentially life
threatening and require early surgical treatment, such as obstruction, hemorrhage
and perforation. There is no consensus on the management of this disease. Only a
few cases of jejunal diverticulosis with midgut volvulus have been reported. We
herein report a case of 57-year-old woman with jejunal diverticulosis causing
small bowel volvulus who complained of intermittent upper abdominal pin-prick for
5 years that eventually progressed to a complete obstruction. The computed
tomography scans revealed a mesenteric vessel "whirlpool" and laparotomy showed
midgut volvulus secondary to jejunal diverticula. This case highlights jejunal
diverticulosis causing small bowel volvulus as an uncommon mechanism of small
bowel obstruction, which should be included in the differential diagnosis of
small bowel obstruction.
PMID- 23155329
TI - Primary squamous cell carcinoma of the liver associated with hepatolithiasis: a
case report.
AB - Primary squamous cell carcinoma (SCC) of the liver is rare and reported
sporadically. Up to date, only 24 such cases have been reported in the
literature. It is associated with hepatic teratoma, congenital cysts, solitary
benign non-parasitic hepatic cysts, hepatolithiasis/Caroli's disease or
cirrhosis. We reported a case of primary SCC of the liver associated with
multiple intrahepatic cholesterol gallstones. The patient underwent hepatectomy
followed by radiotherapy, and has survived for over 19 mo without recurrence.
PMID- 23155330
TI - Signaling pathway/molecular targets and new targeted agents under development in
hepatocellular carcinoma.
AB - Advances in molecular cell biology over the last decade have clarified the
mechanisms involved in cancer growth, invasion, and metastasis, and enabled the
development of molecular-targeted agents. To date, sorafenib is the only
molecular-targeted agent whose survival benefit has been demonstrated in two
global phase III randomized controlled trials, and has been approved worldwide.
Phase III clinical trials of other molecular targeted agents comparing them with
sorafenib as first-line treatment agents are ongoing. Those agents target the
vascular endothelial growth factor, platelet-derived growth factor receptors, as
well as target the epidermal growth factor receptor, insulin-like growth factor
receptor and mammalian target of rapamycin, in addition to other molecules
targeting other components of the signal transduction pathways. In addition, the
combination of sorafenib with standard treatment, such as resection, ablation,
transarterial embolization, and hepatic arterial infusion chemotherapy are
ongoing. This review outlines the main pathways involved in the development and
progression of hepatocellular carcinoma and the new agents that target these
pathways. Finally, the current statuses of clinical trials of new agents or
combination therapy with sorafenib and standard treatment will also be discussed.
PMID- 23155331
TI - PNPLA3, the triacylglycerol synthesis/hydrolysis/storage dilemma, and
nonalcoholic fatty liver disease.
AB - Genome-wide and candidate gene association studies have identified several
variants that predispose individuals to developing nonalcoholic fatty liver
disease (NAFLD). However, the gene that has been consistently involved in the
genetic susceptibility of NAFLD in humans is patatin-like phospholipase domain
containing 3 (PNPLA3, also known as adiponutrin). A nonsynonymous single
nucleotide polymorphism in PNPLA3 (rs738409 C/G, a coding variant that encodes an
amino acid substitution I148M) is significantly associated with fatty liver and
histological disease severity, not only in adults but also in children.
Nevertheless, how PNPLA3 influences the biology of fatty liver disease is still
an open question. A recent article describes new aspects about PNPLA3
gene/protein function and suggests that the I148M variant promotes hepatic lipid
synthesis due to a gain of function. We revise here the published data about the
role of the I148M variant in lipogenesis/lipolysis, and suggest putative areas
of future research. For instance we explored in silico whether the rs738409 C or
G alleles have the ability to modify miRNA binding sites and miRNA gene
regulation, and we found that prediction of PNPLA3 target miRNAs shows two miRNAs
potentially interacting in the 3'UTR region (hsa-miR-769-3p and hsa-miR-516a-3p).
In addition, interesting unanswered questions remain to be explored. For example,
PNPLA3 lies between two CCCTC-binding factor-bound sites that could be tested for
insulator activity, and an intronic histone 3 lysine 4 trimethylation peak
predicts an enhancer element, corroborated by the DNase I hypersensitivity site
peak. Finally, an interaction between PNPLA3 and glycerol-3-phosphate
acyltransferase 2 is suggested by data miming.
PMID- 23155332
TI - Human endogenous retroviruses and cancer: causality and therapeutic
possibilities.
AB - A substantial part of the human genome is derived from transposable elements;
remnants of ancient retroviral infections. Conservative estimates set the
percentage of human endogenous retroviruses (HERVs) in the genome at 8%. For the
most part, the interplay between mutations, epigenetic mechanisms and
posttranscriptional regulations silence HERVs in somatic cells. We first
highlight mechanisms by which activation of members of several HERV families may
be associated with tumor development before discussing the arising chances for
both diagnosis and therapy. It has been shown that at least in some cases, tumor
cells expressing HERV open reading frames (ORFs) thus gain tumor-promoting
functions. However, since these proteins are not expressed in healthy tissues,
they become prime target structures. Of potential pharmacological interest are
the prevention of HERV transposition, the inhibition of HERV-encoded protein
expression and the interference with these proteins' activities. Evidence from
recent studies unequivocally proves that HERV ORFs represent a very interesting
source of novel tumor-specific antigens with even the potential to surpass entity
boundaries. The development of new tumor (immune-) therapies is a very active
field and true tumor-specific targets are of outstanding interest since they
minimize the risk of autoimmunity and could reduce side effects. Finally, we
postulate on main future research streams in order to stimulate discussion on
this hot topic.
PMID- 23155334
TI - Current progress in the treatment of chronic hepatitis C.
AB - Over the last decade, the standard of care for the treatment of chronic hepatitis
C has been the combination of pegylated-interferon-alfa (PEG-IFN) and ribavirin
(RBV) which results in sustained virological response (SVR) rates of 75%-85% in
patients with genotypes 2 or 3 but only of 40%-50% in patients with genotype 1.
Currently, there are rapid and continuous developments of numerous new agents
against hepatitis C virus (HCV), which are the focus of this review. Boceprevir
and telaprevir, two first-generation NS3/4A HCV protease inhibitors, have been
recently licensed in several countries around the world to be used in combination
with PEG-IFN and RBV for the treatment of genotype 1 patients. Boceprevir or
telaprevir based triple regimens, compared with the PEG-IFN/RBV combination,
improve the SVR rates by 25%-31% in treatment-naive genotype 1 patients, by 40%
64% in prior relapsers, by 33%-45% in prior partial responders and by 24%-28% in
prior null responders. At the same time, the application of response-guided
treatment algorithms according to the on-treatment virological response results
in shortening of the total therapy duration to only 24 wk in 45%-55% of treatment
naive patients. There are, however, several challenges with the use of the new
triple combinations in genotype 1 patients, such as the need for immediate
results of HCV RNA testing using sensitive quantitative assays, new and more
frequent adverse events (anemia and dysgeusia for boceprevir; pruritus, rash and
anemia for telaprevir), new drug interactions and increasing difficulties in
compliance. Moreover, the SVR rates are still poor in very difficult to treat
subgroups of genotype 1 patients, such as null responders with cirrhosis, while
there is no benefit for patients who cannot tolerate PEG-IFN/RBV or who are
infected with non-1 HCV genotype. Many newer anti-HCV agents of different classes
and numerous combinations are currently under evaluation with encouraging
results. Preliminary data suggest that the treatment of chronic HCV patients with
well tolerated combinations of oral agents without PEG-IFN is feasible and may
lead to a universal HCV cure over the next 5-10 years.
PMID- 23155335
TI - High densities of serotonin and peptide YY cells in the colon of patients with
lymphocytic colitis.
AB - AIM: To investigate colonic endocrine cells in lymphocytic colitis (LC) patients.
METHODS: Fifty-seven patients with LC were included. These patients were 41
females and 16 males, with an average age of 49 years (range 19-84 years). Twenty
seven subjects that underwent colonoscopy with biopsies were used as controls.
These subjects underwent colonoscopy because of gastrointestinal bleeding or
health worries, where the source of bleeding was identified as haemorrhoids or
angiodysplasia. They were 19 females and 8 males with an average age of 49 years
(range 18-67 years). Biopsies from the right and left colon were obtained from
both patients and controls during colonoscopy. Biopsies were fixed in 4% buffered
paraformaldehyde, embedded in paraffin and cut into 5 MUm-thick sections. The
sections immunostained by the avidin-biotin-complex method for serotonin, peptide
YY (PYY), pancreatic polypeptide (PP) enteroglucagon and somatostatin cells. The
cell densities were quantified by computerised image analysis using Olympus
software. RESULTS: The colon of both the patient and the control subjects were
macroscopically normal. Histopathological examination of colon biopsies from
controls revealed normal histology. All patients fulfilled the diagnosis criteria
required for of LC: an increase in intraepithelial lymphocytes (> 20
lymphocytes/100 epithelial cells) and surface epithelial damage with increased
lamina propria plasma cells and absent or minimal crypt architectural
distribution. In the colon of both patients and control subjects, serotonin-, PYY
, PP-, enteroglucagon- and somatostatin-immunoreactive cells were primarily
located in the upper part of the crypts of Lieberkuhn. These cells were basket-
or flask-shaped. There was no statistically significant difference between the
right and left colon in controls with regards to the densities of serotonin- and
PYY-immunoreactive cells (P = 0.9 and 0.1, respectively). Serotonin cell density
in the right colon in controls was 28.9 +/- 1.8 and in LC patients 41.6 +/- 2.6
(P = 0.008). In the left colon, the corresponding figures were 28.5 +/- 1.9 and
42.4 +/- 2.9, respectively (P = 0.009). PYY cell density in the right colon of
the controls was 10.1 +/- 1 and of LC patients 41 +/- 4 (P = 0.00006). In the
left colon, PYY cell density in controls was 6.6 +/- 1.2 and in LC patients 53.3
+/- 4.6 (P = 0.00007). CONCLUSION: The change in serotonin cells could be caused
by an interaction between immune cells and serotonin cells, and that of PYY
density might be secondary.
PMID- 23155333
TI - Celiac disease: prevalence, diagnosis, pathogenesis and treatment.
AB - Celiac disease (CD) is one of the most common diseases, resulting from both
environmental (gluten) and genetic factors [human leukocyte antigen (HLA) and non
HLA genes]. The prevalence of CD has been estimated to approximate 0.5%-1% in
different parts of the world. However, the population with diabetes, autoimmune
disorder or relatives of CD individuals have even higher risk for the development
of CD, at least in part, because of shared HLA typing. Gliadin gains access to
the basal surface of the epithelium, and interact directly with the immune
system, via both trans- and para-cellular routes. From a diagnostic perspective,
symptoms may be viewed as either "typical" or "atypical". In both positive
serological screening results suggestive of CD, should lead to small bowel biopsy
followed by a favourable clinical and serological response to the gluten-free
diet (GFD) to confirm the diagnosis. Positive anti-tissue transglutaminase
antibody or anti-endomysial antibody during the clinical course helps to confirm
the diagnosis of CD because of their over 99% specificities when small bowel
villous atrophy is present on biopsy. Currently, the only treatment available for
CD individuals is a strict life-long GFD. A greater understanding of the
pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic
gliadin peptide, prevent toxic gliadin peptide absorption, blockage of selective
deamidation of specific glutamine residues by tissue, restore immune tolerance
towards gluten, modulation of immune response to dietary gliadin, and restoration
of intestinal architecture.
PMID- 23155336
TI - Galactosylated chitosan/5-fluorouracil nanoparticles inhibit mouse hepatic cancer
growth and its side effects.
AB - AIM: To observe the curative effect of galactosylated chitosan (GC)/5
fluorouracil (5-FU) nanoparticles in liver caner mice and its side effects.
METHODS: The GC/5-FU nanoparticle is a nanomaterial made by coupling GC and 5-FU.
The release experiment was performed in vitro. The orthotropic liver cancer mouse
models were established and divided into control, GC, 5-FU and GC/5-FU groups.
Mice in the control and GC group received an intravenous injection of 200 MUL
saline and GC, respectively. Mice in the 5-FU and GC/5-FU groups received 200 MUL
(containing 0.371 mg 5-FU) 5-FU and GC/5-FU, respectively. The tumor weight and
survival time were observed. The cell cycle and apoptosis in tumor tissues were
monitored by flow cytometry. The expression of p53, Bax, Bcl-2, caspase-3 and
poly adenosine 50-diphosphate-ribose polymerase 1 (PARP-1) was detected by
immunohistochemistry, reverse transcription-polymerase chain reaction and Western
blot. The serum blood biochemical parameters and cytotoxic activity of natural
killer (NK) cell and cytotoxicity T lymphocyte (CTL) were measured. RESULTS: The
GC/5-FU nanoparticle is a sustained release system. The drug loading was 6.12% +/
1.36%, the encapsulation efficiency was 81.82% +/- 5.32%, and the Zeta potential
was 10.34 +/- 1.43 mV. The tumor weight in the GC/5-FU group (0.4361 +/- 0.1153 g
vs 1.5801 +/- 0.2821 g, P < 0.001) and the 5-FU (0.7932 +/- 0.1283 g vs 1.5801 +/
0.2821 g, P < 0.001) was significantly lower than that in the control group;
GC/5-FU treatment can significantly lower the tumor weight (0.4361 +/- 0.1153 g
vs 0.7932 +/- 0.1283 g, P < 0.001), and the longest median survival time was seen
in the GC/5-FU group, compared with the control (12 d vs 30 d, P < 0.001), GC (13
d vs 30 d, P < 0.001) and 5-FU groups (17 d vs 30 d, P < 0.001). Flow cytometry
revealed that compared with the control, GC/5-FU caused a higher rate of G0-G1
arrest (52.79% +/- 13.42% vs 23.92% +/- 9.09%, P = 0.014 ) and apoptosis (2.55%
+/- 1.10% vs 11.13% +/- 11.73%, P < 0.001) in hepatic cancer cells. Analysis of
the apoptosis pathways showed that GC/5-FU upregulated the expression of p53 at
both the protein and the mRNA levels, which in turn lowered the ratio of Bcl
2/Bax expression; this led to the release of cytochrome C into the cytosol from
the mitochondria and the subsequent activation of caspase-3. Upregulation of
caspase-3 expression decreased the PARP-1 at both the mRNA and the protein
levels, which contributed to apoptosis. 5-FU increased the levels of aspartate
aminotransferase and alanine aminotransferase, and decreased the numbers of
platelet, white blood cell and lymphocyte and cytotoxic activities of CTL and NK
cells, however, there were no such side effects in the GC/5-FU group. CONCLUSION:
GC/5-FU nanoparticles can significantly inhibit the growth of liver cancer in
mice via the p53 apoptosis pathway, and relieve the side effects and
immunosuppression of 5-FU.
PMID- 23155337
TI - Small intestine contrast ultrasonography vs computed tomography enteroclysis for
assessing ileal Crohn's disease.
AB - AIM: To compare computed tomography enteroclysis (CTE) vs small intestine
contrast ultrasonography (SICUS) for assessing small bowel lesions in Crohn's
disease (CD), when using surgical pathology as gold standard. METHODS: From
January 2007 to July 2008, 15 eligible patients undergoing elective resection of
the distal ileum and coecum (or right colon) were prospectively enrolled. All
patients were under follow-up. The study population included 6 males and 9
females, with a median age of 44 years (range: 18-80 years). INCLUSION CRITERIA:
(1) certain diagnosis of small bowel requiring elective ileo-colonic resection;
(2) age between 18-80 years; (3) elective surgery in our Surgical Unit; and (4)
written informed consent. SICUS and CTE were performed <= 3 mo before surgery,
followed by surgical pathology. The following small bowel lesions were blindly
reported by one sonologist, radiologist, surgeon and histolopathologist: disease
site, extent, strictures, abscesses, fistulae, small bowel dilation. Comparison
between findings at SICUS, CTE, surgical specimens and histological examination
was made by assessing the specificity, sensitivity and accuracy of each
technique, when using surgical findings as gold standard. RESULTS: Among the 15
patients enrolled, CTE was not feasible in 2 patients, due to urgent surgery in
one patients and to low compliance in the second patient, refusing to perform CTE
due to the discomfort related to the naso-jejunal tube. The analysis for
comparing CTE vs SICUS findings was therefore performed in 13 out of the 15 CD
patients enrolled. Differently from CTE, SICUS was feasible in all the 15
patients enrolled. No complications were observed when using SICUS or CTE.
Surgical pathology findings in the tested population included: small bowel
stricture in 13 patients, small bowel dilation above ileal stricture in 10
patients, abdominal abscesses in 2 patients, enteric fistulae in 5 patients,
lymphnodes enlargement (> 1 cm) in 7 patients and mesenteric enlargement in 9
patients. In order to compare findings by using SICUS, CTE, histology and
surgery, characteristics of the small bowel lesions observed in CD each patient
were blindly reported in the same form by one gastroenterologist-sonologist,
radiologist, surgeon and anatomopathologist. At surgery, lesions related to CD
were detected in the distal ileum in all 13 patients, also visualized by both
SICUS and CTE in all 13 patients. Ileal lesions > 10 cm length were detected at
surgery in all the 13 CD patients, confirmed by SICUS and CTE in the same 12 out
of the 13 patients. When using surgical findings as a gold standard, SICUS and
CTE showed the exactly same sensitivity, specificity and accuracy for detecting
the presence of small bowel fistulae (accuracy 77% for both) and abscesses
(accuracy 85% for both). In the tested CD population, SICUS and CTE were also
quite comparable in terms of accuracy for detecting the presence of small bowel
strictures (92% vs 100%), small bowel fistulae (77% for both) and small bowel
dilation (85% vs 82%). CONCLUSION: In our study population, CTE and the non
invasive and radiation-free SICUS showed a comparable high accuracy for assessing
small bowel lesions in CD.
PMID- 23155338
TI - Quasispecies dynamics in main core epitopes of hepatitis B virus by ultra-deep
pyrosequencing.
AB - AIM: To investigate the variability of the main immunodominant motifs of
hepatitis B virus (HBV) core gene by ultra-deep-pyrosequencing (UDPS). METHODS:
Four samples (2 genotype A and 2 genotype D) from 4 treatment-naive patients were
assessed for baseline variability. Two additional samples from one patient
(patient 4, genotype D) were selected for analysis: one sample corresponded to a
36-mo treatment-free period from baseline and the other to the time of viral
breakthrough after 18 mo of lamivudine treatment. The HBV region analyzed covered
amino acids 40 to 95 of the core gene, and included the two main epitopic
regions, Th50-69 and B74-84. UDPS was carried out in the Genome Sequencer FLX
system (454 Life Sciences, Roche). After computer filtering of UDPS data based on
a Poisson statistical model, 122,813 sequences were analyzed. The most conserved
position detected by UDPS was analyzed by site-directed mutagenesis and evaluated
in cell culture. RESULTS: Positions with highest variability rates were mainly
located in the main core epitopes, confirming their role as immune-stimulating
regions. In addition, the distribution of variability showed a relationship with
HBV genotype. Patient 1 (genotype A) presented the lowest variability rates and
patient 2 (genotype A) had 3 codons with variability higher than 1%. Patient 3
and 4 (both genotype D) presented 5 and 8 codons with variability higher than 1%,
respectively. The median baseline frequencies showed that genotype A samples had
higher variability in epitopic positions than in the other positions analyzed,
approaching significance (P = 0.07, sample 1 and P = 0.05, sample 2). In
contrast, there were no significant differences in variability between the
epitopic and other positions in genotype D cases. Interestingly, patient 1
presented a completely mutated motif from amino acid 64 to 67 (E64LMT67), which
is commonly recognized by T helper cells. Additionally, the variability observed
in all 4 patients was particularly associated with the E64LMT67 motif. Codons 78
and 79 were highly conserved in all samples, in keeping with their involvement in
the interaction between the HBV virion capsid and the surface antigens (HBsAg).
Of note, codon 76 was even more conserved than codons 78 and 79, suggesting a
possible role in HBsAg interactions or even in hepatitis B e antigen
conformation. Sequential analysis of samples from patient 4 (genotype D)
illustrated the dynamism of the HBV quasispecies, with strong selection of one
minor baseline variant coinciding with a decrease in core variability during the
treatment-free and lamivudine-treated period. The drop in variability seemed to
result from a "steady state" situation of the HBV quasispecies after selection of
the variant with greatest fitness. CONCLUSION: Host immune pressure seems to be
the main cause of HBV core evolution. UDPS analysis is a useful technique for
studying viral quasispecies.
PMID- 23155339
TI - Cost of treating chronic hepatitis B: comparison of current treatment guidelines.
AB - AIM: To compare program costs of chronic hepatitis B (CHB) screening and
treatment using Australian and other published CHB treatment guidelines. METHODS:
Economic modeling demonstrated that in Australia a strategy of hepatocellular
cancer (HCC) prevention in patients with CHB is more cost-effective than current
standard care, or HCC screening. Based upon this model, we developed the B
positive program to optimize CHB management of Australians born in countries of
high CHB prevalence. We estimated CHB program costs using the B positive program
algorithm and compared them to estimated costs of using the CHB treatment
guidelines published by the Asian-Pacific, American and European Associations for
the Study of Liver Disease (APASL, AASLD, EASL) and those suggested by an
independent United States hepatology panel. We used a Markov model that factored
in the costs of CHB screening and treatment, individualized by viral load and
alanine aminotransferase levels, and calculated the relative costs of program
components. Costs were discounted by 5% and calculated in Australian dollars
(AUD). RESULTS: Using the B positive algorithm, total program costs amount to
13,979,224 AUD, or 9634 AUD per patient. The least costly strategy is based upon
using the AASLD guidelines, which would cost 34% less than our B positive
algorithm. Using the EASL and the United States Expert Group guidelines would
increase program costs by 46%. The largest expenditure relates to the cost of
drug treatment (66.9% of total program costs). The contribution of CHB
surveillance (20.2%) and HCC screening and surveillance (6.6%) is small--and
together they represent only approximately a quarter of the total program costs.
CONCLUSION: The significant cost variations in CHB screening and treatment using
different guidelines are relevant for clinicians and policy makers involved in
designing population-based disease control programs.
PMID- 23155340
TI - Anemia after gastrectomy for early gastric cancer: long-term follow-up
observational study.
AB - AIM: To identify the incidence and etiology of anemia after gastrectomy in
patients with long-term follow-up after gastrectomy for early gastric cancer.
METHODS: The medical records of those patients with early gastric adenocarcinoma
who underwent curative gastrectomy between January 2006 and October 2007 were
reviewed. Patients with anemia in the preoperative workup, cancer recurrence,
undergoing systemic chemotherapy, with other medical conditions that can cause
anemia, or treated during follow up with red cell transfusions or supplements for
anemia were excluded. Anemia was defined by World Health Organization criteria
(Hb < 12 g/dL in women and < 13 g/dL in men). Iron deficiency was defined as
serum ferritin < 20 MUg/dL. Vitamin B12 deficiency was defined as serum vitamin
B12 < 200 pg/mL. Iron deficiency anemia was defined as anemia with concomitant
iron deficiency. Anemia from vitamin B12 deficiency was defined as megaloblastic
anemia (mean cell volume > 100 fL) with vitamin B12 deficiency. The profile of
anemia over 48 mo of follow-up was analyzed. RESULTS: One hundred sixty-one
patients with gastrectomy for early gastric cancer were analyzed. The incidence
of anemia was 24.5% at 3 mo after surgery and increased up to 37.1% at 48 mo
after surgery. The incidence of iron deficiency anemia increased during the
follow up and became the major cause of anemia at 48 mo after surgery. Anemia of
chronic disease and megaloblastic anemia were uncommon. The incidence of anemia
in female patients was significantly higher than in male patients at 12 (40.0% vs
22.0%, P = 0.033), 24 (45.0% vs 25.0%, P = 0.023), 36 (55.0% vs 28.0%, P =
0.004), and 48 mo (52.0% vs 31.0%, P = 0.022) after surgery. Patients with total
gastrectomy showed significantly higher incidence of anemia than patients with
subtotal gastrectomy at 48 mo after surgery (60.7% vs 31.3%, P = 0.008). The
incidence of iron deficiency was significantly higher in female patients than in
male patients at 6 (35.4% vs 13.3%, P = 0.002), 12 (45.8% vs 16.8%, P < 0.001),
18 (52.1% vs 22.3%, P < 0.001), 24 (60.4% vs 20.9%, P < 0.001), 36 (62.5% vs
29.2%, P < 0.001), and 48 mo (66.7% vs 34.7%, P = 0.001) after surgery.
CONCLUSION: Anemia was frequent after gastrectomy for early gastric cancer, with
iron deficiency being the major cause. Evaluation for anemia including iron
status should be performed after gastrectomy and appropriate iron replacement
should be considered.
PMID- 23155341
TI - Association of chronic viral hepatitis B with insulin resistance.
AB - AIM: To investigate the relationship between chronic viral hepatitis B (CVHB) and
insulin resistance (IR) in Korean adults. METHODS: A total of 7880 adults (3851
men, 4029 women) who underwent a comprehensive medical examination were enrolled
in this study. Subjects diagnosed with either diabetes mellitus, or any other
disorder that could influence their insulin sensitivity, were rejected.
Anthropometry, metabolic risk factors, hepatitis B surface antigen, hepatitis B
surface antibody, hepatitis B core antibody, fasting plasma glucose and insulin
were measured for all subjects. Homeostasis model assessment (HOMA), quantitative
insulin check index (QUICKI), and Mf(fm) index were used for determining insulin
sensitivity. Each participant was categorized into a negative, recovery, or CVHB
group. To compare variables between groups, a t-test and/or one-way analysis of
variance were used. Partial correlation coefficients were computed to present the
association between insulin resistance and other variables. Multiple logistic
regression analysis was used to assess the independent association between CVHB
and IR. RESULTS: The mean age of men and women were 48.9 and 48.6 years,
respectively. Subjects in the CVHB group had significantly higher waist
circumference [(86.0 +/- 7.7 cm vs 87.3 +/- 7.8 cm, P = 0.004 in men), (78.3 +/-
8.6 cm vs 80.5 +/- 8.5 cm, P < 0.001 in women)], cystatin C [(0.96 +/- 0.15 mg/dL
vs 1.02 +/- 0.22 mg/dL, P < 0.001 in men), (0.84 +/- 0.15 mg/dL vs 0.90 +/- 0.16
mg/dL, P < 0.001 in women)], fasting insulin [(5.47 +/- 3.38 MUU/mL vs 6.12 +/-
4.62 MUU/mL, P < 0.001 in men), (4.57 +/- 2.82 MUU/mL vs 5.06 +/- 3.10 MUU/mL, P
< 0.001 in women)] and HOMA index [(1.24 +/- 0.86 vs 1.43 +/- 1.24, P < 0.001 in
men), (1.02 +/- 0.76 vs 1.13 +/- 0.87, P = 0.033 in women)] compared to control
group. The HOMA index revealed a positive correlation with body mass index (BMI)
(r = 0.378, P < 0.001), waist circumference (r =0.356, P < 0.001), percent body
fat (r = 0.296, P < 0.001), systolic blood pressure (r = 0.202, P < 0.001), total
cholesterol (r = 0.134, P < 0.001), triglycerides (r = 0.292, P < 0.001),
cystatin C (r = 0.069, P < 0.001) and uric acid (r = 0.142, P < 0.001). The
QUICKI index revealed a negative correlation with BMI (r = -0.254, P < 0.001),
waist circumference (r = 0-0.243, P < 0.001), percent body fat (r = -0.217, P <
0.001), systolic blood pressure (r = -0.132, P < 0.001), total cholesterol (r =
0.106, P < 0.001), triglycerides (r = -0.205, P < 0.001), cystatin C (r = -0.044,
P < 0.001) and uric acid (r = -0.096, P < 0.001). For subjects identified with
IR, the odds ratio of an accompanying diagnosis of chronic hepatitis B was 1.534
(95% CI: 1.158-2.031, HOMA index criteria) or 1.566 (95% CI: 1.124-2.182, QUICKI
criteria) after adjustment for age, gender, BMI, and amount of alcohol
consumption. CONCLUSION: Our study demonstrates that CVHB is associated with IR.
CVHB may need to be monitored for occurrence of IR and diabetes mellitus.
PMID- 23155342
TI - Treatment of functional dyspepsia with sertraline: a double-blind randomized
placebo-controlled pilot study.
AB - AIM: To evaluate sertraline, a selective serotonin reuptake inhibitor in the
treatment of patients with functional dyspepsia. METHODS: Consecutive tertiary
hospital patients with a clinical diagnosis of functional dyspepsia (FD)
according to the Rome II criteria with a Hong Kong dyspepsia index (HKDI) of
greater than 16 were recruited. Patients commenced enrolment prior to the
inception of the Rome III criteria for functional dyspepsia. All patients were
ethnic Chinese, had a normal upper endoscopy and were Helicobacter pylori
negative prior to enrolment. Study patients were randomized to receive sertraline
50 mg or placebo daily for 8 wk. HKDI symptom scores, quality of life, hospital
anxiety and depression (HAD) scale and global symptom relief were evaluated
before, during and after treatment. Adverse effects were monitored during and
after treatment. RESULTS: A total of 193 patients were randomized in the
intention to treat (ITT), and 150 patients were included in the per protocol (PP)
analysis. In both the ITT and PP, there was no difference in the primary outcome
of global dyspepsia symptoms between the sertraline and placebo groups at week 8.
In the ITT analysis, 98 and 95 patients were randomized to the sertraline and
placebo groups respectively. A total of 43 patients withdrew from the study
(22.3%) by week 8, with 23 of the 24 drop-outs in the sertraline group occurring
prior to week 4 (95.8%). In contrast, in the placebo arm, 11 of 19 patients
dropped out by week 4 (57.9%). Utilizing the last response carried forward to
account for the drop-outs, there were no differences between the sertraline and
placebo groups at baseline in terms of the HKDI, HKDI 26.08 +/- 6.19 vs 26.70 +/-
5.89, P = 0.433; and at week 8, HKDI 22.41 +/- 6.36 vs 23.25 +/- 7.30, P = 0.352
respectively. In the PP analysis, 74 and 76 patients were randomized to the
sertraline and placebo groups respectively. At baseline, there were no
statistically significant differences between the sertraline and placebo groups,
HKDI 25.83 +/- 6.313 vs 27.19 +/- 5.929 respectively, P = 0.233; however by week
8, patients in the sertraline group demonstrated a statistically significant
difference in their Hong Kong Dyspepsia Index compared to placebo, HKDI 20.53 +/-
6.917 vs 23.34 +/- 7.199, P = 0.02, respectively). There was also no
statistically significant difference in overall quality of life measures or the
HAD scale related to treatment in either the ITT or PP analysis at week 8.
CONCLUSION: This pilot study, the first to examine sertraline, a selective
serotonin reuptake inhibitor, for the management of FD, did not find that it was
superior to placebo.
PMID- 23155343
TI - Transcatheter arterial chemoembolization for gastrointestinal stromal tumors with
liver metastases.
AB - AIM: To evaluate the efficacy and safety of transcatheter arterial
chemoembolization (TACE) for gastrointestinal stromal tumor (GIST) with liver
metastases after the failure of tyrosine kinase inhibitors (TKIs). METHODS:
Patients with histologically confirmed CD117-positive GIST with liver metastases
who were resistant and/or intolerant to prior imatinib and/or sunitinib and who
received TACE for at least one treatment cycle or only best supportive care and
TKI reintroduction were eligible for the study. The patients were divided into
two groups: those in TACE group received TACE treatment containing 5-20 mL
iodized oil and 40-80 mg doxorubicin hydrochloride and TKI reintroduction or best
supportive care, those in control group only received TKI reintroduction or best
supportive care. The primary end-point was overall survival and the secondary end
points were, progression-free survival (PFS), response rates, and safety.
RESULTS: Sixty patients admitted between June 2008 and October 2011 were eligible
for this study, including 22 in TACE group and 38 in control group. In the TACE
group, 12 (54.5%) achieved liver partial response, 5 (22.7%) had stable disease,
and 5 (22.7%) had liver progressive disease. Disease control rate of liver
metastases was 77.3% in the TACE group and 39.5% in the control group. The median
liver PFS in TACE group was 47.1 wk (95% CI: 23.9-70.3). The median PFS in TACE
group was longer than in control group (30.0 wk, 95% CI: 20.1-39.9 vs 12.9 wk,
95% CI: 11.9-13.9) (P = 0.0001). The median overall survival in TACE group was
also longer than in control group (68.5 wk, 95% CI: 57.4-79.6 vs 25.7 wk, 95% CI:
23.2-28.2) (P = 0.0001). TACE treatment significantly reduced the risk of death
(hazard ratio: 0.109). Patients without extrahepatic metastases treated with TACE
had significantly better prognosis. Most of the adverse events were of grade 1 or
2 and tolerable. CONCLUSION: TACE is effective and well tolerated in GIST
patients with liver metastases after TKI failure, and it may be an optional
treatment for this disease.
PMID- 23155344
TI - Liver-protecting effects of omega-3 fish oil lipid emulsion in liver
transplantation.
AB - AIM: To investigate the liver-protecting effect of parenteral nutrition (PN)
support with omega-3 fatty acids in a randomized controlled clinical trial.
METHODS: Sixty-six patients with the diagnosis of end-stage liver disease or
hepatic cellular carcinoma were admitted to the Affiliated Drum Tower Hospital,
Nanjing University, China for orthotopic liver transplantation. The patients were
randomly divided into two groups: PN group (n = 33) and polyunsaturated fatty
acid (PUFA) group (n = 33). All patients received isocaloric and isonitrogenous
PN for seven days after surgery, and in PUFA group omega-3 fish oil lipid
emulsion replaced part of the standard lipid emulsion. Liver function was tested
on days 2 and 9 after surgery. Pathological examination was performed after
reperfusion of the donor liver and on day 9. Clinical outcome was assessed based
on the post-transplant investigations, including: (1) post-transplant mechanical
ventilation; (2) total hospital stay; (3) infectious morbidities; (4) acute and
chronic rejection; and (5) mortality (intensive care unit mortality, hospital
mortality, 28-d mortality, and survival at a one-year post-transplant
surveillance period). RESULTS: On days 2 and 9 after operation, a significant
decrease of alanine aminotransferase (299.16 U/L +/- 189.17 U/L vs 246.16 U/L +/-
175.21 U/L, P = 0.024) and prothrombin time (5.64 s +/- 2.06 s vs 2.54 s +/- 1.15
s, P = 0.035) was seen in PUFA group compared with PN group. The pathological
results showed that omega-3 fatty acid supplement improved the injury of hepatic
cells. Compared with PN group, there was a significant decrease of post
transplant hospital stay in PUFA group (18.7 d +/- 4.0 d vs 20.6 d +/- 4.6 d, P =
0.041). Complications of infection occurred in 6 cases of PN group (2 cases of
pneumonia, 3 cases of intra-abdominal abscess and 1 case of urinary tract
infection), and in 3 cases of PUFA group (2 cases of pneumonia and 1 case of
intra-abdominal abscess). No acute or chronic rejection and hospital mortality
were found in both groups. The one-year mortality in PN group was 9.1% (3/33),
one died of pulmonary infection, one died of severe intra-hepatic cholangitis and
hepatic dysfunction and the other died of hepatic cell carcinoma recurrence. Only
one patient in PUFA group (1/33, 3.1%) died of biliary complication and hepatic
dysfunction during follow-up. CONCLUSION: Post-transplant parenteral nutritional
support combined with omega-3 fatty acids can significantly improve the liver
injury, reduce the infectious morbidities, and shorten the post-transplant
hospital stay.
PMID- 23155345
TI - Colorectal cancer lymph node staining by activated carbon nanoparticles
suspension in vivo or methylene blue in vitro.
AB - AIM: To investigate whether activated carbon nanoparticles suspension (ACNS) or
methylene blue (MB) can increase the detected number of lymph nodes in colorectal
cancer. METHODS: Sixty-seven of 72 colorectal cancer patients treated at our
hospital fulfilled the inclusion criteria of the study which was conducted from
December 2010 to February 2012. Seven patients refused to participate.
Eventually, 60 patients were included, and randomly assigned to three groups (20
in each group): ACNS group (group A), MB group (group B) and non-stained
conventional surgical group (group C). In group A, patients received subserosal
injection of 1 mL ACNS in a 4-quadrant region around the mass. In group B, the
main artery of specimen was identified and isolated after the specimen was
removed, and 2 mL MB was slowly injected into the isolated, stretched and fixed
vessel. In group C, no ACNS and MB were injected. All the mesentery lymph nodes
were isolated and removed systematically by visually inspecting and palpating the
adipose tissue. RESULTS: No difference was observed among the three groups in
age, gender, tumor location, tumor diameter, T-stage, degree of differentiation,
postoperative complications and peritoneal drainage retention time. The total
number of detected lymph nodes was 535, 476 and 223 in the three groups,
respectively. The mean number of detected lymph nodes per patient was
significantly higher in group A than in group C (26.8 +/- 8.4 vs 12.2 +/- 3.2, P
< 0.001). Similarly, there were significantly more lymph nodes detected in group
B than in group C (23.8 +/- 6.9 vs 12.2 +/- 3.2, P < 0.001). However, there was
no significant difference between group A and group B. There were 50, 46 and 32
metastatic lymph nodes dissected in 13 patients of group A, 10 patients of group
B and 11 patients of group C, without significant differences among the three
groups. Eleven of the 60 patients had insufficient number of detected lymph nodes
(< 12). Only one patient with T(4a) rectal cancer had 10 lymph nodes detected in
group B, the other 10 patients were all from group C. Based on the different
diameter categories, the number of detected lymph nodes in groups A and B was
significantly higher than in group C. However, there was no statistically
significant difference between group A and group B. The metastatic lymph nodes
were not significant different among the three groups. Similarly, tumor location,
T stage and tumor differentiation did not affect the staining results. Body mass
index was a minor influencing factor in the two different staining methods. The
stained lymph nodes can easily be identified from the mesenteric adipose tissues,
and the staining time for lymph nodes was not significantly different compared
with unstained group. None of the patients in groups A and B had drug-related
complications. CONCLUSION: Both activated carbon nanoparticles suspension in vivo
and methylene blue in vitro can be used as tracers to increase the detected
number of lymph nodes in colorectal cancer.
PMID- 23155346
TI - Inverted Meckel's diverticulum as a cause of occult lower gastrointestinal
hemorrhage.
AB - Meckel's diverticulum is a common asymptomatic congenital gastrointestinal
anomaly, but rarely it can present with hemorrhage. Over the last few years
inverted Meckel's diverticulum has been reported in the literature with
increasing frequency as an occult source of lower gastrointestinal hemorrhage.
Here, we report a case of a 54-year-old male, who was referred for surgical
evaluation with persistent anemia and occult blood per rectum after a work up
which failed to localize the source over 12 mo, including upper and capsule
endoscopy, colonoscopy, enteroclysis, Meckel scan, and tagged nuclear red blood
cell scan. An abdominal computed tomography scan showed a possible mid-ileal
intussusception and intraluminal mass. During the abdominal exploration, inverted
Meckel's diverticulum was diagnosed and resected. We review the literature,
discuss the forms in which the disease presents, the diagnostic modalities
utilized, pathological findings, and treatment. Although less than 40 cases have
been reported in the English literature from 1978 to 2005, 19 cases have been
reported in the last 6 years alone (2006-2012) due to improved diagnostic
modalities. Successful diagnosis and treatment of this disease requires a high
index of clinical suspicion, which is becoming increasingly relevant to general
gastroenterologists.
PMID- 23155347
TI - Enterolithiasis-associated ileus in Crohn's disease.
AB - Stasis of the flow of the intestinal contents, ingested material and unfavorable
composition of the chylus can lead to the formation of enteroliths inside the
bowel. Enterolithiasis represents a rare disorder of the gastrointestinal tract
that can be associated with intermittent abdominal pain or more serious
complications such as bleeding or obstruction. Enterolithiasis in Crohn's disease
represents an extremely rare condition and usually occurs only in patients with a
long symptomatic history of Crohn's disease. We report an unusual case of
enterolithiasis-related intestinal obstruction in a young male patient with
Crohn's disease (A2L3B1 Montreal Classification for Crohn's disease 2005)
undergoing emergency laparotomy and ileocoecal resection. In addition, we present
an overview of the relevant characteristics of enterolithiasis on the basis of
the corresponding literature.
PMID- 23155348
TI - An aortoduodenal fistula as a complication of immunoglobulin G4-related disease.
AB - Most primary aortoduodenal fistulas occur in the presence of an aortic aneurysm,
which can be part of immunoglobulin G4 (IgG4)-related sclerosing disease. We
present a case who underwent endovascular grafting of an aortoduodenal fistula
associated with a high serum IgG4 level. A 56-year-old male underwent urgent
endovascular reconstruction of an aortoduodenal fistula. The patient received
antibiotics and other supportive therapy, and the postoperative course was
uneventful, however, elevated levels of serum IgG, IgG4 and C-reactive protein
were noted, which normalized after the introduction of steroid therapy. Control
computed tomography angiography showed no endoleaks. The primary aortoduodenal
fistula may have been associated with IgG4-related sclerosing disease as a
possible complication of IgG4-related inflammatory aortic aneurysm. Endovascular
grafting of a primary aortoduodenal fistula is an effective and minimally
invasive alternative to standard surgical repair.
PMID- 23155349
TI - Should anticoagulants be administered for portal vein thrombosis associated with
acute pancreatitis?
AB - Venous complications in patients with acute pancreatitis typically occur as a
form of splenic, portal, or superior mesenteric vein thrombosis and have been
detected more frequently in recent reports. Although a well-organized protocol
for the treatment of venous thrombosis has not been established, anticoagulation
therapy is commonly recommended. A 73-year-old man was diagnosed with acute
progressive portal vein thrombosis associated with acute pancreatitis. After one
month of anticoagulation therapy, the patient developed severe hematemesis. With
endoscopy and an abdominal computed tomography scan, hemorrhages in the
pancreatic pseudocyst, which was ruptured into the duodenal bulb, were confirmed.
After conservative treatment, the patient was stabilized. While the rupture of a
pseudocyst into the surrounding viscera is a well-known phenomenon, spontaneous
rupture into the duodenum is rare. Moreover, no reports of upper gastrointestinal
bleeding caused by pseudocyst rupture in patients under anticoagulation therapy
for venous thrombosis associated with acute pancreatitis have been published.
Herein, we report a unique case of massive upper gastrointestinal bleeding due to
pancreatic pseudocyst rupture into the duodenum, which developed during
anticoagulation therapy for portal vein thrombosis associated with acute
pancreatitis.
PMID- 23155350
TI - Postoperative retroperitoneal desmoid tumor mimics recurrent gastrointestinal
stromal tumor: a case report.
AB - Desmoid tumor is a locally invasive, myofibroblastic, nonmetastatic tumor. Its
pathogenesis remains unclear and it may involve genetic abnormalities, sex
hormones and traumatic injury, including surgery. Postoperative intra-abdominal
desmoid tumor is rare, especially in the retroperitoneum. We report a case of
postoperative retroperitoneal desmoid tumor that developed 29 mo after the first
excision of a gastrointestinal stromal tumor. Sporadic trauma-related intra
abdominal desmoid tumors reported in the English literature are also reviewed.
Despite an extremely low incidence, postoperative desmoid tumor should be
considered in the differential diagnosis when a recurrent neoplasm is found at
least one year after operation. However, it is a clinical challenge to
distinguish recurrent malignant neoplasms from desmoid tumors, and surgical
resection is the treatment option depending on the anatomic location.
PMID- 23155351
TI - Penalized Nonlinear Least Squares Estimation of Time-Varying Parameters in
Ordinary Differential Equations.
AB - Ordinary differential equations (ODEs) are widely used in biomedical research and
other scientific areas to model complex dynamic systems. It is an important
statistical problem to estimate parameters in ODEs from noisy observations. In
this article we propose a method for estimating the time-varying coefficients in
an ODE. Our method is a variation of the nonlinear least squares where penalized
splines are used to model the functional parameters and the ODE solutions are
approximated also using splines. We resort to the implicit function theorem to
deal with the nonlinear least squares objective function that is only defined
implicitly. The proposed penalized nonlinear least squares method is applied to
estimate a HIV dynamic model from a real dataset. Monte Carlo simulations show
that the new method can provide much more accurate estimates of functional
parameters than the existing two-step local polynomial method which relies on
estimation of the derivatives of the state function. Supplemental materials for
the article are available online.
PMID- 23155352
TI - Media and politics: Empirical data on their cross-influence in health policy.
AB - OBJECTIVES: Despite the central influence of public policies on health and
welfare, relatively little is known about actual health care policy-making
processes. This presentation will offer preliminary results from a federally
funded project aimed at gaining insights into the interrelations among interest
group strategies, media discourses and political debates in health care. The
policy debate on health care privatization in Quebec is used as a case study.
APPROACH: Two sources of data were used: media sources and political debates.
Media sources were the six main provincial newspapers in Quebec, two national
newspapers and The Canadian Press, as well as transcripts from specific news
related programs of three national television stations and two national radio
stations. Political debates were obtained through transcripts of all question
periods in the Parliament and debates in the standing committee on health.
Sources were systematically searched to identify all relevant data. Multiple
search syntaxes were developed and tested to maximize sensitivity and
specificity. All data was entered and coded into qualitative analysis software.
RESULTS: Data was analyzed longitudinally from June 2005 to January 1, 2010. Four
levels of results will be presented: 1) Descriptive analysis of the interest
groups involved, their policy preferences and the rhetoric they employed to
support their views. 2) Descriptive analysis of the main policy proposals that
structured the debate as well as of the coalition of groups behind those
proposals. 3) Graphic longitudinal analysis of the intensity of the debate and of
the relative importance and evolution of various policy proposals. 4) Preliminary
results on the nature, direction and level of inter-influence between the policy
and media agendas. CONCLUSION: This presentation provides empirical evidence on
current policy-making processes in health care. It shows, unsurprisingly, that
policy-making is a circumvoluted process of inter-influence among interest
groups, politicians and the media. It also highlights the fact that scientific
evidence actually plays a minor (if any) role in policy processes.
PMID- 23155353
TI - Bothaella manhi, a new species of tribe Aedini (Diptera: Culicidae) from the Cuc
Phuong National Park of Vietnam based on morphology and DNA sequence.
AB - A new species of genus Bothaella (Diptera: Culicidae) collected along with two
other species of the genus during surveys for flavivirus isolations in the Cuc
Phuong National Park in northern Vietnam is formally described and named as
Bothaella manhi, sp. n. The adults, pupa and fourth-instar larva are
characterized, the male genitalia and the two immature stages are illustrated and
DNA sequence data are included for regions coding for sections of the COI and
COII genes (mtDNA). The species is compared and distinguished from the other
species of the genus, and sequence data are used to hypothesise its phylogenetic
relationship with Bo. helenae and Bo. kleini, the other two species collected
during the survey.
PMID- 23155354
TI - Target-target similarity on the attentional blink: Task-relevance matters!
AB - Studies of the attentional blink (AB) indicate that similarity modulates the
magnitude of the impairment in reporting the second of two masked targets. The
present experiments tested whether similarity-based modulations of the AB are
determined by all object dimensions or by task-relevant dimensions only.
Similarity between target faces was manipulated on two dimensions, only one of
which was task-relevant. The results indicated that similarity on the task
relevant dimension modulated the AB, while similarity on task-irrelevant
dimension did not. These results suggest that selection during the AB can occur
on the level of task-relevant dimensions.
PMID- 23155355
TI - Requirements for contractility in disordered cytoskeletal bundles.
AB - Actomyosin contractility is essential for biological force generation, and is
well understood in highly organized structures such as striated muscle.
Additionally, actomyosin bundles devoid of this organization are known to
contract both in vivo and in vitro, which cannot be described by standard muscle
models. To narrow down the search for possible contraction mechanisms in these
systems, we investigate their microscopic symmetries. We show that contractile
behavior requires non-identical motors that generate large-enough forces to probe
the nonlinear elastic behavior of F-actin. This suggests a role for filament
buckling in the contraction of these bundles, consistent with recent experimental
results on reconstituted actomyosin bundles.
PMID- 23155356
TI - VEGF -634C/G genotype is predictive of long-term survival after treatment with a
definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients
with esophageal squamous cell carcinoma.
AB - BACKGROUND: Reports have been accumulating that genetic properties are predictive
of clinical response after and/or toxicity during cancer chemotherapy, but little
information is available concerning effects on long-term survival. In this study,
49 Japanese patients with esophageal squamous cell carcinoma (ESCC) were followed
up for 5 years after treatment with a definitive 5-fluorouracil (5-FU)/cisplatin
(CDDP)-based chemoradiotherapy (CRT), and the effects of genotypes of vascular
endothelial growth factor (VEGF) were retrospectively revaluated in terms of
prediction of long-term survival. METHODS: A course consisted of the continuous
infusion of 5-FU at 400 mg/m(2)/day for days 1-5 and 8-12, the infusion of CDDP
at 40 mg/m(2)/day on days 1 and 8, and radiation at 2 Gy/day on days 1 to 5, 8 to
12, and 15 to 19, with a second course repeated after a 2-week interval. The VEGF
genotypes -1498T/C, -1154G/A, -634C/G, -7C/T, 936C/T, and 1612G/A were evaluated.
RESULTS: The complete response (CR) rate was 46.9% (23/49). The 5-year survival
rate was 42.9 % (21/49). There were 7 patients with a CR, but survival of less
than 5 years. They died from myocardial infarction (N=1), sudden cardiac death
after suffering from heart failure (N=1), acute myeloid leukemia that developed
from myelodysplastic syndromes (N=1), factors not specified (N=2), oropharynx
cancer (N=1), and tongue cancer (N=1). VEGF -634C/G had no effect on clinical
response, but long-term survival depended on the genotype (p=0.033, Fisher's;
p=0.038, Cochran-Armitage; p=0.079, Log-rank). The genotype frequency of 7
patients with a CR, but survival of less than 5 years was different from that for
the other 42 patients (p=0.032, Fisher's). None of the other 5 genotypes
evaluated affected either clinical response or survival. CONCLUSIONS: VEGF
634C/G is possibly predictive of long-term survival after treatment with a
definitive 5-FU/CDDP-based CRT. Further clinical studies with a larger number of
cases are needed to clarify the effects of this genotype.
PMID- 23155357
TI - Inhibitory effects of anthocyanins on secretion of Helicobacter pylori CagA and
VacA toxins.
AB - Anthocyanins have been studied as potential antimicrobial agents against
Helicobacter pylori. We investigated whether the biosynthesis and secretion of
cytotoxin-associated protein A (CagA) and vacuolating cytotoxin A (VacA) could be
suppressed by anthocyanin treatment in vitro. H. pylori reference strain 60190
(CagA(+)/VacA(+)) was used in this study to investigate the inhibitory effects of
anthocyanins; cyanidin 3-O-glucoside (C3G), peonidin 3-O-glucoside (Peo3G),
pelargonidin 3-O-glucoside (Pel3G), and malvidin 3-O-glucoside (M3G) on
expression and secretion of H. pylori toxins. Anthocyanins were added to
bacterial cultures and Western blotting was used to determine secretion of CagA
and VacA. Among them, we found that C3G inhibited secretion of CagA and VacA
resulting in intracellular accumulation of CagA and VacA. C3G had no effect on
cagA and vacA expression but suppressed secA transcription. As SecA is involved
in translocation of bacterial proteins, the down-regulation of secA expression by
C3G offers a mechanistic explanation for the inhibition of toxin secretion. To
our knowledge, this is the first report suggesting that C3G inhibits secretion of
the H. pylori toxins CagA and VacA via suppression of secA transcription.
PMID- 23155358
TI - Curative resection of hepatocellular carcinoma using modified Glissonean pedicle
transection versus the Pringle maneuver: a case control study.
AB - OBJECTIVE: The Glissonean pedicle transection method of liver resection has been
found to shorten operative time and minimize intraoperative bleeding during liver
segmentectomy. We have compared the feasibility, effectiveness, and safety of the
Glissonean pedicle transection method with the Pringle maneuver in patients
undergoing selective curative resection of large hepatocellualr carcinoma (HCC).
METHODS: Eligible patients with large (> 5 cm) nodular HCC (n = 50) were assigned
to undergo curative hepatectomy using the Glissonean pedicle transection method
(n = 25) or the Pringle maneuver (n = 25). Partial interruption of the
infrahepatic inferior vena cava was incorporated to further reduce bleeding from
liver transection. The primary outcome measure was postoperative changes in liver
function from baseline. Secondary outcomes included operating time, volume of
intraoperative blood loss/transfusion, and time to resolution of ascites.
RESULTS: The two groups were comparable in age, sex, site and size of the liver
tumor, segment or lobe intended to be resected, and liver function reserve, and
the results were not significant statistically. All patients underwent successful
major hepatectomies using the assigned method, with the extent of major
hepatectomy comparable in the two groups (P = 0.832). The Glissonean approach was
associated with shorter hepatic inflow interruption (30.0 +/- 12.0 min vs. 45.0
+/- 13.0 min, P < 0.001), lower volume of blood loss (145.0 +/- 20.0 mL vs. 298.0
+/- 109.0 mL, P < 0.001), reduced requirement for transfusion (0.0 +/- 0.0 mL vs.
200.0 +/- 109.0 mL, P < 0.0001), and more rapid resolution of ascites (9.5 +/-
1.2 d vs. 15.3 +/- 2.4 d, P < 0.001). Postoperative liver function measures were
comparable in the two groups, and the results were not significant statistically.
CONCLUSION: The Glissonean pedicle transection method is a feasible, effective,
and safe technique for hepatic inflow control during the curative resection of
large nodular HCCs.
PMID- 23155359
TI - Effect of low-level laser therapy on incorporation of block allografts.
AB - OBJECTIVE: To assess the effect of low-level laser therapy (LLLT) on the
incorporation of deep-frozen block allografts in a rabbit model. BACKGROUND DATA:
Studies have shown that LLLT has beneficial effects on tissue repair and new bone
formation. METHODS: Bone tissue was harvested from two rabbits, processed by deep
freezing and grafted into the calvaria of 12 animals, which were then randomly
allocated into two groups: experimental (L) and control (C). Rabbits in group L
were irradiated with an aluminum gallium arsenide diode laser (AlGaAs; wavelength
830 nm, 4 J/cm(2)), applied to four sites on the calvaria, for a total dose of 16
J/cm(2) per session. The total treatment dose after eight sessions was 128
J/cm(2). Animals were euthanized at 35 (n = 6) or 70 days (n = 6)
postoperatively. RESULTS: Deep-freeze-processed block allografts followed by LLLT
showed incorporation at the graft-host interface, moderate bone remodeling,
partial filling of osteocyte lacunae, less inflammatory infiltrate in the early
postoperative period, and higher collagen deposition than the control group.
CONCLUSION: Optical microscopy and scanning electron microscopy showed that
allograft bone processed by deep-freezing plus LLLT is suitable as an alternative
for the treatment of bone defects. Use of the deep-freezing method for processing
of bone grafts preserves the structural and osteoconductive characteristics of
bone tissue.
PMID- 23155360
TI - Bone morphogenetic protein-9 induces osteogenic differentiation of rat dental
follicle stem cells in P38 and ERK1/2 MAPK dependent manner.
AB - Dental follicle stem cells are a group of cells possessing osteogenic,
adipogenetic and neurogenic differentiations, but the specific mechanism
underlying the multilineage differentiation remains still unclear. Great
attention has been paid to bone morphogenetic protein-9 (BMP-9) due to its potent
osteogenic activity. In the present study, rat dental follicle stem cells were
isolated and purified, and cells of passage 3 underwent adenovirus mediated BMP-9
gene transfection to prepare dental follicle stem cells with stable BMP-9
expression. Detection of alkaline phosphatase (ALP) and calcium deposition showed
dental follicle stem cells transfected with BMP-9 gene could significantly
promote the osteogenesis. In addition, SB203580 and PD98059 were employed to
block the p38 mitogen-activated protein kinase (p38MAPK) and extracellular signal
regulated kinase (ERK1/2), respectively. Detection of ALP and calcium deposition
revealed the BMP-9 induced osteogenic differentiation of dental follicle stem
cells depended on MAPK signaling pathway.
PMID- 23155361
TI - Platelet Rich Fibrin (P.R.F.) in reconstructive surgery of atrophied maxillary
bones: clinical and histological evaluations.
AB - INTRODUCTION: Maxillary bone losses often require additional regenerative
procedures: as a supplement to the procedures of tissue regeneration, a platelet
concentrate called PRF (Platelet Rich Fibrin) was tested for the first time in
France by Dr. Choukroun. Aim of the present study is to investigate, clinically
and histologically, the potential use of PRF, associated with deproteinized
bovine bone (Bio-Oss), as grafting materials in pre-implantology sinus grafting
of severe maxillary atrophy, in comparison with a control group, in which only
deproteinized bovine bone (Bio-Oss) was used as reconstructive material.
MATERIALS AND METHODS: 60 patients were recruited using the cluster-sampling
method; inclusion criteria were maxillary atrophy with residual ridge < 5mm. The
major atrophies in selected patients involved sinus-lift, with a second-look
reopening for the implant insertion phase. The used grafting materials were: a)
Bio-Oss and b) amorphous and membranous PRF together with Bio-Oss. We performed
all operations by means of piezosurgery in order to reduce trauma and to optimize
the design of the operculum on the cortical bone. The reopening of the surgical
area was scheduled at 3 different times. RESULTS: 72 sinus lifts were performed
with subsequent implants insertions.We want to underline how the histological
results proved that the samples collected after 106 days (Early protocol) with
the adding of PRF were constituted by lamellar bone tissue with an interposed
stroma that appeared relaxed and richly vascularized. CONCLUSIONS: The use of PRF
and piezosurgery reduced the healing time, compared to the 150 days described in
literature, favoring optimal bone regeneration. At 106 days, it is already
possible to achieve good primary stability of endosseous implants, though lacking
of functional loading.
PMID- 23155362
TI - Molecular mechanism of SAHA on regulation of autophagic cell death in tamoxifen
resistant MCF-7 breast cancer cells.
AB - OBJECTIVE: Tamoxifen is currently used for the treatment of estrogen receptor
positive breast cancer patients, but acquired resistance to tamoxifen is a
critical problem in breast cancer therapy. Suberoylanilide hydroxamic acid (SAHA)
is a prototype of the newly developed HDAC inhibitor. The aim of this study is to
investigate the anticancer effects of SAHA in tamoxifen-resistant MCF-7 (TAMR/MCF
7) cells. METHODS: Cytotoxicity, apoptosis and autophagic cell death induced by
SAHA were studied. A TAMR/MCF-7 cells xenograft model was established to
investigate the inhibitory effect of SAHA on tumor growth in vivo. RESULTS: SAHA
inhibited the proliferation of TAMR/MCF-7 cells in a dose-dependent manner. SAHA
significantly reduced the expression of HDAC1, 2, 3, 4 and 7 and increased
acetylated histone H3 and H4. Although SAHA induced G2/M phase arrest of cell
cycle, apoptotic cell death was very low, which is correlated with the slight
change in the activation of caspases and PARP cleavage. Interestingly, expression
of the autophagic cell death markers, LC3-II and beclin-1, was significantly
increased in TAMR/MCF-7 cells treated with SAHA. Autophagic cell death induced by
SAHA was confirmed by acridine orange staining and transmission electron
microscopy (TEM) in TAMR/MCF-7 cells. In mice bearing the TAMR/MCF-7 cell
xenografts, SAHA significantly reduced the tumor growth and weight, without
apparent side effects. CONCLUSION: These results suggest that SAHA can induce
caspase-independent autophagic cell death rather than apoptotic cell death in
TAMR/MCF-7 cells. SAHA-mediated autophagic cell death is a promising new strategy
to treatment of tamoxifen-resistant human breast cancer.
PMID- 23155363
TI - Three-dimensional ultrasound appearance of pelvic floor in nulliparous women and
pelvic organ prolapse women.
AB - The present study investigated the morphology and structure of pelvic floor in 50
nulliparous and 50 pelvic organ prolapse (POP) women using translabial three
dimensional (3D) ultrasound. The levator hiatus in POP women was significantly
different from that in nullipara women. In POP women, the size of pelvic floor
increased, with a circular shape, and the axis of levator hiatus departed from
the normal position in 36 (72%) cases. The puborectalis was avulsed in 18 (36%)
cases and the pelvic organs arranged abnormally in 23 (46%) cases. In summary, 3D
ultrasound is an effective tool to detect the pelvic floor in POP women who
presented with abnormalities in the morphology and structure of pelvic floor.
PMID- 23155364
TI - Quantification of BCR-ABL mRNA in plasma/serum of patients with chronic
myelogenous leukemia.
AB - Quantification of tumor-associated mRNA extracted from blood cells/tissues
containing tumor cells is used for evaluation of treatment efficacy or residual
tumor cell burden in tumors including leukemia. However, this method using tumor
cell-containing blood/tissue is difficult to evaluate the whole tumor cell burden
in the body. In order to establish an efficient method to evaluate the whole
tumor cell burden in the body, we tried to quantify tumor-associated mRNA
existing in plasma/serum instead of leukemia cell-containing blood cells in
patients with chronic myelogenous leukemia (CML) and compared the levels of BCR
ABL mRNA between plasma/serum and peripheral blood cells. mRNA of BCR-ABL, WT1 or
GAPDH (control molecule) was detected by real-time RT-PCR using RNA extracted
from plasma/serum of almost all the patients with CML. Copy numbers of BCR-ABL
mRNA were significantly correlated between plasma/serum and peripheral blood
cells. However, levels of BCR-ABL mRNA extracted from serum were low compared
with those extracted with peripheral blood cells. The present findings suggest
that although real-time RT-PCR of mRNA existing in plasma/serum could be used for
evaluating the whole tumor cell burden in the body, it's required to establish an
efficient method to quantify plasma/serum mRNA by nature without degrading during
the procedure.
PMID- 23155365
TI - Impact of Trauma on Attenuated Psychotic Symptoms.
AB - Evidence that trauma may play a role in the development of a psychotic illness
has lead researchers to investigate the relationship between trauma and the
content of attenuated psychotic symptoms. Participants in this study were
considered to be at clinical high risk for developing psychosis by meeting
criteria for attenuated positive symptom syndrome based on the Structured
Interview for Prodromal Syndromes. Trained raters used a specifically designed
codebook to identify content in the vignettes of 45 participants. Various types
of trauma that had occurred before age 16 were assessed, where participants who
endorsed more types of trauma were considered to have experienced a greater
amount of trauma. Spearman rank correlations revealed significant positive
relationships between increased trauma and feeling watched or followed (rho=0.38,
p<0.05) and false beliefs of status or power (rho=0.31, p<0.04). Significant
negative relationships were observed between increased trauma and hearing
nonnegative voices (rho=-0.39, p<0.01) as well as having unusual negative
thoughts surrounding the self (rho=-0.31, p<0.05). Although this was a small
sample, these findings support the possibility of a meaningful relationship
between experiences of trauma and the content of attenuated positive symptoms.
PMID- 23155366
TI - Social role patterning in early adulthood in the USA: adolescent predictors and
concurrent wellbeing across four distinct configurations.
AB - The decade following secondary school is pivotal in setting the stage for
adulthood functioning and adjustment. We identify four social role configurations
of early adults in their mid-20s using latent class analyses in two nationally
representative samples of American youth in their last year of secondary
education (modal age 18) who were followed longitudinally into adulthood (age
25/26). We focus on the big five social role domains of early adulthood:
education, residential status, employment, cohabitation/marriage, and parenthood.
Aims were to identify latent classes of social role configurations in early
adulthood, examine demographic and late adolescent educational predictors of
these classes, and explore contemporaneous health and adjustment correlates
focusing on life satisfaction, economic independence, and substance use. Four
classes with very similar characteristics and prevalence were identified in the
two cohorts who were born 12 years apart: Educated Students without Children (8%
in 80s cohort/9% in 90s cohort); Working Singles Living with Parents (16%/18%);
Educated Workers without Children (45%/46%); and Married Workers with Children
(31%/27%). Late adolescent demographic and educational variables and mid-20s
variables were related to class membership. Results evidenced notable
similarities (and some differences) across cohorts. Discussion focuses on how
roles facilitate or inhibit each other and the potential diversity of optimal
patterns of transitions to adulthood.
PMID- 23155367
TI - Impact of asthma on educational attainment in a socioeconomically deprived
population: a study linking health, education and social care datasets.
AB - BACKGROUND: Asthma has the potential to adversely affect children's school
examination performance, and hence longer term life chances. Asthma morbidity is
especially high amongst UK ethnic minority children and those experiencing social
adversity, populations which also have poor educational outcomes. We tested the
hypothesis that asthma adversely affects performance in national school
examinations in a large cohort from an area of ethnic diversity and social
deprivation. METHODS AND FINDINGS: With a novel method (using patient and address
matching algorithms) we linked administrative and clinical data for 2002-2005 for
children in east London aged 5-14 years to contemporaneous education and social
care datasets. We modelled children's performance in school examinations in
relation to socio-demographic and clinical variables. The dataset captured
examination performance for 12,136 children who sat at least one national
examination at Key Stages 1-3. For illustration, estimates are presented as
percentage changes in Key Stage 2 results. Having asthma was associated with a
1.1% increase in examination scores (95%CI 0.4 to 1.7)%,p = 0.02. Worse scores
were associated with Bangladeshi ethnicity -1.3%(-2.5 to -0.1)%,p = 0.03; special
educational need -14.6%(-15.7 to -13.5)%,p = 0.02; mental health problems -2.5%(
4.1 to -0.9)%,p = 0.003, and social adversity: living in a smoking household
1.2(-1.7 to -0.6)%,p<0.001; living in social housing -0.8%(-1.3 to -0.2)% p =
0.01, and entitlement to free school meals -0.8%(-1.5 to -0.1)%,p<0.001.
CONCLUSIONS: Social adversity and ethnicity, but not asthma, are associated with
poorer performance in national school examinations. Policies to improve
educational attainment in socially deprived areas should focus on these factors.
PMID- 23155368
TI - Neural responses to smoking stimuli are influenced by smokers' attitudes towards
their own smoking behaviour.
AB - An important feature of addiction is the high drug craving that may promote the
continuation of consumption. Environmental stimuli classically conditioned to
drug-intake have a strong motivational power for addicts and can elicit craving.
However, addicts differ in the attitudes towards their own consumption behavior:
some are content with drug taking (consonant users) whereas others are discontent
(dissonant users). Such differences may be important for clinical practice
because the experience of dissonance might enhance the likelihood to consider
treatment. This fMRI study investigated in smokers whether these different
attitudes influence subjective and neural responses to smoking stimuli. Based on
self-characterization, smokers were divided into consonant and dissonant smokers.
These two groups were presented smoking stimuli and neutral stimuli. Former
studies have suggested differences in the impact of smoking stimuli depending on
the temporal stage of the smoking ritual they are associated with. Therefore, we
used stimuli associated with the beginning (BEGIN-smoking-stimuli) and stimuli
associated with the terminal stage (END-smoking-stimuli) of the smoking ritual as
distinct stimulus categories. Stimulus ratings did not differ between both
groups. Brain data showed that BEGIN-smoking-stimuli led to enhanced mesolimbic
responses (amygdala, hippocampus, insula) in dissonant compared to consonant
smokers. In response to END-smoking-stimuli, dissonant smokers showed reduced
mesocortical responses (orbitofrontal cortex, subcallosal cortex) compared to
consonant smokers. These results suggest that smoking stimuli with a high
incentive value (BEGIN-smoking-stimuli) are more appetitive for dissonant than
consonant smokers at least on the neural level. To the contrary, smoking stimuli
with low incentive value (END-smoking-stimuli) seem to be less appetitive for
dissonant smokers than consonant smokers. These differences might be one reason
why dissonant smokers experience difficulties in translating their attitudes into
an actual behavior change.
PMID- 23155369
TI - Modeling and molecular dynamics of HPA-1a and -1b polymorphisms: effects on the
structure of the beta3 subunit of the alphaIIbbeta3 integrin.
AB - BACKGROUND: The HPA-1 alloimmune system carried by the platelet integrin
alphaIIbbeta3 is the primary cause of alloimmune thrombocytopenia in Caucasians
and the HPA-1b allele might be a risk factor for thrombosis. HPA-1a and -1b
alleles are defined by a leucine and a proline, respectively, at position 33 in
the beta3 subunit. Although the structure of alphaIIbbeta3 is available, little
is known about structural effects of the L33P substitution and its consequences
on immune response and integrin functions. METHODOLOGY/PRINCIPAL FINDINGS: A
complete 3D model of the L33-beta3 extracellular domain was built and a P33 model
was obtained by in silico mutagenesis. We then performed molecular dynamics
simulations. Analyses focused on the PSI, I-EGF-1, and I-EGF-2 domains and
confirmed higher exposure of residue 33 in the L33 beta3 form. These analyses
also showed major structural flexibility of all three domains in both forms, but
increased flexibility in the P33 beta3 form. The L33P substitution does not alter
the local structure (residues 33 to 35) of the PSI domain, but modifies the
structural equilibrium of the three domains. CONCLUSIONS: These results provide a
better understanding of HPA-1 epitopes complexity and alloimmunization prevalence
of HPA-1a. P33 gain of structure flexibility in the beta3 knee may explain the
increased adhesion capacity of HPA-1b platelets and the associated thrombotic
risk. Our study provides important new insights into the relationship between HPA
1 variants and beta3 structure that suggest possible effects on the alloimmune
response and platelet function.
PMID- 23155370
TI - Skeletogenic fate of zebrafish cranial and trunk neural crest.
AB - The neural crest (NC) is a major contributor to the vertebrate craniofacial
skeleton, detailed in model organisms through embryological and genetic
approaches, most notably in chick and mouse. Despite many similarities between
these rather distant species, there are also distinct differences in the
contribution of the NC, particularly to the calvariae of the skull. Lack of
information about other vertebrate groups precludes an understanding of the
evolutionary significance of these differences. Study of zebrafish craniofacial
development has contributed substantially to understanding of cartilage and bone
formation in teleosts, but there is currently little information on NC
contribution to the zebrafish skeleton. Here, we employ a two-transgene system
based on Cre recombinase to genetically label NC in the zebrafish. We demonstrate
NC contribution to cells in the cranial ganglia and peripheral nervous system
known to be NC-derived, as well as to a subset of myocardial cells. The indelible
labeling also enables us to determine NC contribution to late-forming bones,
including the calvariae. We confirm suspected NC origin of cartilage and bones of
the viscerocranium, including cartilages such as the hyosymplectic and its
replacement bones (hymandibula and symplectic) and membranous bones such as the
opercle. The cleithrum develops at the border of NC and mesoderm, and as an
ancestral component of the pectoral girdle was predicted to be a hybrid bone
composed of both NC and mesoderm tissues. However, we find no evidence of a NC
contribution to the cleithrum. Similarly, in the vault of the skull, the parietal
bones and the caudal portion of the frontal bones show no evidence of NC
contribution. We also determine a NC origin for caudal fin lepidotrichia; the
presumption is that these are derived from trunk NC, demonstrating that these
cells have the ability to form bone during normal vertebrate development.
PMID- 23155371
TI - Inferences from the historical distribution of wild and domesticated maize
provide ecological and evolutionary insight.
AB - BACKGROUND: The species Zea mays includes both domesticated maize (ssp. mays) and
its closest wild relatives known as the teosintes. While genetic and
archaeological studies have provided a well-established history of Z. mays
evolution, there is currently minimal description of its current and past
distribution. Here, we implemented species distribution modeling using
paleoclimatic models of the last interglacial (LI; ~135,000 BP) and the last
glacial maximum (LGM; ~21,000 BP) to hindcast the distribution of Zea mays
subspecies over time and to revisit current knowledge of its phylogeography and
evolutionary history. METHODOLOGY/PRINCIPAL FINDINGS: Using a large occurrence
data set and the distribution modeling MaxEnt algorithm, we obtained robust
present and past species distributions of the two widely distributed teosinte
subspecies (ssps. parviglumis and mexicana) revealing almost perfect
complementarity, stable through time, of their occupied distributions. We also
investigated the present distributions of primitive maize landraces, which
overlapped but were broader than those of the teosintes. Our data reinforced the
idea that little historical gene flow has occurred between teosinte subspecies,
but maize has served as a genetic bridge between them. We observed an expansion
of teosinte habitat from the LI, consistent with population genetic data.
Finally, we identified locations potentially serving as refugia for the teosintes
throughout epochs of climate change and sites that should be targeted in future
collections. CONCLUSION/SIGNIFICANCE: The restricted and highly contrasting
ecological niches of the wild teosintes differ substantially from domesticated
maize. Variables determining the distributions of these taxa can inform future
considerations of local adaptation and the impacts of climate change. Our
assessment of the changing distributions of Zea mays taxa over time offers a
unique glimpse into the history of maize, highlighting a strategy for the study
of domestication that may prove useful for other species.
PMID- 23155372
TI - Mimicking insect communication: release and detection of pheromone,
biosynthesized by an alcohol acetyl transferase immobilized in a microreactor.
AB - Infochemical production, release and detection of (Z,E)-9,11-tetradecadienyl
acetate, the major component of the pheromone of the moth Spodoptera littoralis,
is achieved in a novel microfluidic system designed to mimic the final step of
the pheromone biosynthesis by immobilized recombinant alcohol acetyl transferase.
The microfluidic system is part of an "artificial gland", i.e., a chemoemitter
that comprises a microreactor connected to a microevaporator and is able to
produce and release a pre-defined amount of the major component of the pheromone
from the corresponding (Z,E)-9,11-tetradecadienol. Performance of the entire
chemoemitter has been assessed in electrophysiological and behavioral
experiments. Electroantennographic depolarizations of the pheromone produced by
the chemoemitter were ca. 40% relative to that evoked by the synthetic pheromone.
In a wind tunnel, the pheromone released from the evaporator elicited on males a
similar attraction behavior as 3 virgin females in most of the parameters
considered.
PMID- 23155373
TI - Programmable in vivo selection of arbitrary DNA sequences.
AB - The extraordinary fidelity, sensory and regulatory capacity of natural
intracellular machinery is generally confined to their endogenous environment.
Nevertheless, synthetic bio-molecular components have been engineered to
interface with the cellular transcription, splicing and translation machinery in
vivo by embedding functional features such as promoters, introns and ribosome
binding sites, respectively, into their design. Tapping and directing the power
of intracellular molecular processing towards synthetic bio-molecular inputs is
potentially a powerful approach, albeit limited by our ability to streamline the
interface of synthetic components with the intracellular machinery in vivo. Here
we show how a library of synthetic DNA devices, each bearing an input DNA
sequence and a logical selection module, can be designed to direct its own
probing and processing by interfacing with the bacterial DNA mismatch repair
(MMR) system in vivo and selecting for the most abundant variant, regardless of
its function. The device provides proof of concept for programmable, function
independent DNA selection in vivo and provides a unique example of a logical
functional interface of an engineered synthetic component with a complex
endogenous cellular system. Further research into the design, construction and
operation of synthetic devices in vivo may lead to other functional devices that
interface with other complex cellular processes for both research and applied
purposes.
PMID- 23155374
TI - Antibody to Epstein-Barr virus deoxyuridine triphosphate nucleotidohydrolase and
deoxyribonucleotide polymerase in a chronic fatigue syndrome subset.
AB - BACKGROUND: A defined diagnostic panel differentiated patients who had been
diagnosed with chronic fatigue syndrome (CFS), based upon Fukuda/Carruthers
criteria. This diagnostic panel identified an Epstein-Barr virus (EBV) subset of
patients (6), excluding for the first time other similar "clinical" conditions
such as cytomegalovirus (CMV), human herpesvirus 6 (HHV6), babesiosis,
ehrlichiosis, borreliosis, Mycoplasma pneumoniae, Chlamydia pneumoniae, and adult
rheumatic fever, which may be mistakenly called CFS. CFS patients were treated
with valacyclovir (14.3 mg/kg q6h) for >= 12 months. Each patient improved, based
upon the Functional Activity Appraisal: Energy Index Score Healthcare Worker
Assessment (EIPS), which is a validated (FSS-9), item scale with high degree of
internal consistency measured by Cronbach's alpha. METHODS: Antibody to EBV viral
capsid antigen (VCA) IgM, EBV Diffuse Early Antigen EA(D), and neutralizing
antibodies against EBV-encoded DNA polymerase and EBV-encoded dUTPase were
assayed serially approximately every three months for 13-16 months from sera
obtained from patients with CFS (6) and from sera obtained from twenty patients
who had no history of CFS. RESULTS: Antibodies to EBV EA(D) and neutralizing
antibodies against the encoded-proteins EBV DNA polymerase and deoxyuridine
triphosphate nucleotidohydrolase (dUTPase) were present in the EBV subset CFS
patients. Of the sera samples obtained from patients with CFS 93.9% were positive
for EA(D), while 31.6% of the control patients were positive for EBV EA(D). Serum
samples were positive for neutralizing antibodies against the EBV-encoded dUTPase
(23/52; 44.2%) and DNA polymerase (41/52; 78.8%) in EBV subset CFS patients, but
negative in sera of controls. CONCLUSIONS: There is prolonged elevated antibody
level against the encoded proteins EBV dUTPase and EBV DNA polymerase in a subset
of CFS patients, suggesting that this antibody panel could be used to identify
these patients, if these preliminary findings are corroborated by studies with a
larger number of EBV subset CFS patients.
PMID- 23155375
TI - The mobilization and recruitment of c-kit+ cells contribute to wound healing
after surgery.
AB - Delayed wound healing is a serious clinical problem in patients after surgery. A
recent study has demonstrated that bone marrow-derived c-kit-positive (c-kit(+))
cells play important roles in repairing and regenerating various tissues and
organs. To examine the hypothesis that surgical injury induces the mobilization
and recruitment of c-kit+ cells to accelerate wound healing. Mice were subjected
to a left pneumonectomy. The mobilization of c-kit+ cells was monitored after
surgery. Using green fluorescent protein (GFP(+)) bone marrow-transplanted
chimera mice, we investigated further whether the mobilized c-kit+ cells were
recruited to effect wound healing in a skin puncture model. The group with left
pneumonectomies increased the c-kit(+) and CD34(+) stem cells in peripheral blood
24 h after surgery. At 3 days after surgery, the skin wound size was observed to
be significantly smaller, and the number of bone marrow-derived GFP(+) cells and
GFP(+)/c-kit+ cells in the wound tissue was significantly greater in mice that
had received pneumonectomies, as compared with those that had received a sham
operation. Furthermore, some of these GFP(+) cells were positively expressed
specific markers of macrophages (F4/80), endothelial cells (CD31), and
myofibroblasts (alphaSMA). The administration of AMD3100, an antagonist of a
stromal-cell derived factor (SDF)-1/CXCR4 signaling pathway, reduced the number
of GFP(+) cells in wound tissue and completely negated the accelerated wound
healing. Surgical injury induces the mobilization and recruitment of c-kit+ cells
to contribute to wound healing. Regulating c-kit+ cells may provide a new
approach that accelerates wound healing after surgery.
PMID- 23155376
TI - Bacterial colony from two-dimensional division to three-dimensional development.
AB - On agar surface, bacterial daughter cells form a 4-cell array after the first two
rounds of division, and this phenomenon has been previously attributed to a
balancing of interactions among the daughter bacteria and the underneath agar. We
studied further the organization and development of colony after additional
generations. By confocal laser scanning microscopy and real-time imaging, we
observed that bacterial cells were able to self-organize and resulted in a near
circular micro-colony consisting of monolayer cells. After continuous dividing,
bacteria transited from two-dimensional expansion into three-dimensional growth
and formed two to multi-layers in the center but retained a monolayer in the
outer ring of the circular colony. The transverse width of this outer ring
appeared to be approximately constant once the micro-colony reached a certain
age. This observation supports the notion that balanced interplays of the forces
involved lead to a gross morphology as the bacteria divide into offspring on agar
surface. In this case, the result is due to a balance between the expansion force
of the dividing bacteria, the non-covalent force among bacterial offspring and
that between bacteria and substratum.
PMID- 23155377
TI - A remarkable case of micro-endemism in Laonastes aenigmamus (Diatomyidae,
Rodentia) revealed by nuclear and mitochondrial DNA sequence data.
AB - L. aenigmamus is endemic to the limestone formations of the Khammuan Province
(Lao PDR), and is strongly specialized ecologically. From the survey of 137
individuals collected from 38 localities, we studied the phylogeography of this
species using one mitochondrial (Cyt b) and two nuclear genes (BFIBR and GHR).
Cyt b analyses reveal a strong mtDNA phylogeographical structure: 8 major
geographical clades differing by 5-14% sequence divergence were identified, most
of them corresponding to distinct karst areas. Nuclear markers display congruent
results but with a less genetic structuring. Together, the data strongly suggest
an inland insular model for Laonastes population structure. With 8 to 16
evolutionary significant units in a small area (about 200*50 km) this represents
an exceptional example of micro-endemism. Our results suggest that L. aenigmamus
may represent a complex of species and/or sub-species. The common ancestor of all
Laonastes may have been widely distributed within the limestone formations of the
Khammuan Province at the end of Miocene/beginning of the Pliocene. Parallel
events of karst fragmentation and population isolation would have occurred during
the Pleistocene or/and the end of the Pliocene. The limited gene flow detected
between populations from different karst blocks restrains the likelihood of
survival of Laonastes. This work increases the necessity for a strict protection
of this rare animal and its habitat and provides exclusive information, essential
to the organization of its protection.
PMID- 23155378
TI - Bats in a farming landscape benefit from linear remnants and unimproved pastures.
AB - Schemes designed to make farming landscapes less hostile to wildlife have been
questioned because target taxa do not always respond in the expected manner.
Microbats are often overlooked in this process, yet persist in agricultural
landscapes and exert top-down control of crop pests. We investigated the
relationship between microbats and measures commonly incorporated into agri
environment schemes, to derive management recommendations for their ongoing
conservation. We used acoustic detectors to quantify bat species richness,
activity, and feeding in 32 linear remnants and adjacent fields across an
agricultural region of New South Wales, Australia. Nocturnal arthropods were
simultaneously trapped using black-light traps. We recorded 91,969 bat calls,
17,277 of which could be attributed to one of the 13 taxa recorded, and 491 calls
contained feeding buzzes. The linear remnants supported higher bat activity than
the fields, but species richness and feeding activity did not significantly
differ. We trapped a mean 87.6 g (+/-17.6 g SE) of arthropods per night, but
found no differences in biomass between land uses. Wider linear remnants with
intact native vegetation supported more bat species, as did those adjacent to
unsealed, as opposed to sealed roads. Fields of unimproved native pastures, with
more retained scattered trees and associated hollows and logs, supported the
greatest bat species richness and activity. We conclude that the juxtaposition of
linear remnants of intact vegetation and scattered trees in fields, coupled with
less-intensive land uses such as unimproved pastures will benefit bat communities
in agricultural landscapes, and should be incorporated into agri-environment
schemes. In contrast, sealed roads may act as a deterrent. The "wildlife friendly
farming" vs "land sparing" debate has so far primarily focussed on birds, but
here we have found evidence that the integration of both approaches could
particularly benefit bats.
PMID- 23155379
TI - Phylogeny and evolutionary patterns in the Dwarf crayfish subfamily (Decapoda:
Cambarellinae).
AB - The Dwarf crayfish or Cambarellinae, is a morphologically singular subfamily of
decapod crustaceans that contains only one genus, Cambarellus. Its intriguing
distribution, along the river basins of the Gulf Coast of United States (Gulf
Group) and into Central Mexico (Mexican Group), has until now lacked of
satisfactory explanation. This study provides a comprehensive sampling of most of
the extant species of Cambarellus and sheds light on its evolutionary history,
systematics and biogeography. We tested the impact of Gulf Group versus Mexican
Group geography on rates of cladogenesis using a maximum likelihood framework,
testing different models of birth/extinction of lineages. We propose a
comprehensive phylogenetic hypothesis for the subfamily based on mitochondrial
and nuclear loci (3,833 bp) using Bayesian and Maximum Likelihood methods. The
phylogenetic structure found two phylogenetic groups associated to the two main
geographic components (Gulf Group and Mexican Group) and is partially consistent
with the historical structure of river basins. The previous hypothesis, which
divided the genus into three subgenera based on genitalia morphology was only
partially supported (P = 0.047), resulting in a paraphyletic subgenus
Pandicambarus. We found at least two cases in which phylogenetic structure failed
to recover monophyly of recognized species while detecting several cases of
cryptic diversity, corresponding to lineages not assigned to any described
species. Cladogenetic patterns in the entire subfamily are better explained by an
allopatric model of speciation. Diversification analyses showed similar
cladogenesis patterns between both groups and did not significantly differ from
the constant rate models. While cladogenesis in the Gulf Group is coincident in
time with changes in the sea levels, in the Mexican Group, cladogenesis is
congruent with the formation of the Trans-Mexican Volcanic Belt. Our results show
how similar allopatric divergence in freshwater organisms can be promoted through
diverse vicariant factors.
PMID- 23155380
TI - Different regional gray matter loss in recent onset PTSD and non PTSD after a
single prolonged trauma exposure.
AB - OBJECTIVE: Gray matter loss in the limbic structures was found in recent onset
post traumatic stress disorder (PTSD) patients. In the present study, we measured
regional gray matter volume in trauma survivors to verify the hypothesis that
stress may cause different regional gray matter loss in trauma survivors with and
without recent onset PTSD. METHOD: High resolution T1-weighted magnetic resonance
imaging (MRI) were obtained from coal mine flood disaster survivors with (n = 10)
and without (n = 10) recent onset PTSD and 20 no trauma exposed normal controls.
The voxel-based morphometry (VBM) method was used to measure the regional gray
matter volume in three groups, the correlations of PTSD symptom severities with
the gray matter volume in trauma survivors were also analyzed by multiple
regression. RESULTS: Compared with normal controls, recent onset PTSD patients
had smaller gray matter volume in left dorsal anterior cingulate cortex (ACC),
and non PTSD subjects had smaller gray matter volume in the right pulvinar and
left pallidum. The gray matter volume of the trauma survivors correlated
negatively with CAPS scores in the right frontal lobe, left anterior and middle
cingulate cortex, bilateral cuneus cortex, right middle occipital lobe, while in
the recent onset PTSD, the gray matter volume correlated negatively with CAPS
scores in bilateral superior medial frontal lobe and right ACC. CONCLUSION: The
present study identified gray matter loss in different regions in recent onset
PTSD and non PTSD after a single prolonged trauma exposure. The gray matter
volume of left dorsal ACC associated with the development of PTSD, while the gray
matter volume of right pulvinar and left pallidum associated with the response to
the severe stress. The atrophy of the frontal and limbic cortices predicts the
symptom severities of the PTSD.
PMID- 23155381
TI - Transforming growth factor alpha (TGFalpha) regulates granulosa cell tumor (GCT)
cell proliferation and migration through activation of multiple pathways.
AB - Granulosa cell tumors (GCTs) are the most common ovarian estrogen producing
tumors, leading to symptoms of excessive estrogen such as endometrial hyperplasia
and endometrial adenocarcinoma. These tumors have malignant potential and often
recur. The etiology of GCT is unknown. TGFalpha is a potent mitogen for many
different cells. However, its function in GCT initiation, progression and
metastasis has not been determined. The present study aims to determine whether
TGFalpha plays a role in the growth of GCT cells. KGN cells, which are derived
from an invasive GCT and have many features of normal granulosa cells, were used
as the cellular model. Immunohistochemistry, Western blot and RT-PCR results
showed that the ErbB family of receptors is expressed in human GCT tissues and
GCT cell lines. RT-PCR results also indicated that TGFalpha and EGF are expressed
in the human granulosa cells and the GCT cell lines, suggesting that TGFalpha
might regulate GCT cell function in an autocrine/paracrine manner. TGFalpha
stimulated KGN cell DNA synthesis, cell proliferation, cell viability, cell cycle
progression, and cell migration. TGFalpha rapidly activated EGFR/PI3K/Akt and
mTOR pathways, as indicated by rapid phosphorylation of Akt, TSC2, Rictor, mTOR,
P70S6K and S6 proteins following TGFalpha treatment. TGFalpha also rapidly
activated the EGFR/MEK/ERK pathway, and P38 MAPK pathways, as indicated by the
rapid phosphorylation of EGFR, MEK, ERK1/2, P38, and CREB after TGFalpha
treatment. Whereas TGFalpha triggered a transient activation of Akt, it induced a
sustained activation of ERK1/2 in KGN cells. Long-term treatment of KGN cells
with TGFalpha resulted in a significant increase in cyclin D2 and a decrease in
p27/Kip1, two critical regulators of granulosa cell proliferation and granulosa
cell tumorigenesis. In conclusion, TGFalpha, via multiple signaling pathways,
regulates KGN cell proliferation and migration and may play an important role in
the growth and metastasis of GCTs.
PMID- 23155383
TI - Using co-occurrence to evaluate belief coherence in a large non clinical sample.
AB - Much of the recent neuropsychological literature on false beliefs (delusions) has
tended to focus on individual or single beliefs, with few studies actually
investigating the relationship or co-occurrence between different types of co
existing beliefs. Quine and Ullian proposed the hypothesis that our beliefs form
an interconnected web in which the beliefs that make up that system must somehow
"cohere" with one another and avoid cognitive dissonance. As such beliefs are
unlikely to be encapsulated (i.e., exist in isolation from other beliefs). The
aim of this preliminary study was to empirically evaluate the probability of
belief co-occurrence as one indicator of coherence in a large sample of subjects
involving three different thematic sets of beliefs (delusion-like, paranormal &
religious, and societal/cultural). Results showed that the degree of belief co
endorsement between beliefs within thematic groupings was greater than random
occurrence, lending support to Quine and Ullian's coherentist account. Some
associations, however, were relatively weak, providing for well-established
examples of cognitive dissonance.
PMID- 23155382
TI - Direct angiotensin II type 2 receptor stimulation ameliorates insulin resistance
in type 2 diabetes mice with PPARgamma activation.
AB - OBJECTIVES: The role of angiotensin II type 2 (AT(2)) receptor stimulation in the
pathogenesis of insulin resistance is still unclear. Therefore we examined the
possibility that direct AT(2) receptor stimulation by compound 21 (C21) might
contribute to possible insulin-sensitizing/anti-diabetic effects in type 2
diabetes (T2DM) with PPARgamma activation, mainly focusing on adipose tissue.
METHODS: T2DM mice, KK-Ay, were subjected to intraperitoneal injection of C21
and/or a PPARgamma antagonist, GW9662 in drinking water for 2 weeks. Insulin
resistance was evaluated by oral glucose tolerance test, insulin tolerance test,
and uptake of 2-[(3)H] deoxy-D-glucose in white adipose tissue. Morphological
changes of adipose tissues as well as adipocyte differentiation and inflammatory
response were examined. RESULTS: Treatment with C21 ameliorated insulin
resistance in KK-Ay mice without influencing blood pressure, at least partially
through effects on the PPARgamma pathway. C21 treatment increased serum
adiponectin concentration and decreased TNF-alpha concentration; however, these
effects were attenuated by PPARgamma blockade by co-treatment with GW9662.
Moreover, we observed that administration of C21 enhanced adipocyte
differentiation and PPARgamma DNA-binding activity, with a decrease in
inflammation in white adipose tissue, whereas these effects of C21 were
attenuated by co-treatment with GW9662. We also observed that administration of
C21 restored beta cell damage in diabetic pancreatic tissue. CONCLUSION: The
present study demonstrated that direct AT(2) receptor stimulation by C21
accompanied with PPARgamma activation ameliorated insulin resistance in T2DM
mice, at least partially due to improvement of adipocyte dysfunction and
protection of pancreatic beta cells.
PMID- 23155384
TI - Antibodies against Marinobacter algicola and Salmonella typhimurium flagellins do
not cross-neutralize TLR5 activation.
AB - Flagellins evoke strong innate and adaptive immune responses. These proteins may
play a key role as radioprotectors, exert antitumoral activity in certain types
of tumor and reduce graft-versus-host disease in allogeneic hematopoietic stem
cell transplant recipients. Notwithstanding, flagellins are highly immunogenic,
and repeated use leads to their neutralization by systemic antibodies. This
neutralization is not prevented by using functional deleted flagellins. These
observations led us to explore the possibility of preventing initial
neutralization by means of another functional flagellin that does not belong to
common pathogenic bacteria but that has the capacity to activate TLR5. Here we
characterized the functional capacity of the two-phase Marinobacter algicola (MA)
derived flagellins (F and FR) as systemic and mucosal adjuvants and compared
their performance with that of Salmonella typhimurium (STF) flagellins (FljB and
FliC). We also report for the first time on the in vitro and in vivo capacity of
various flagellins to trigger TLR5 activation in the presence of species-specific
anti-flagellin antibodies, the cross-neutralization mediated by these antibodies,
and the sequential use of these flagellins for TLR5 activation. Our results
showed that MA flagellins behave in a similar way to STF ones, inducing pro
inflammatory cytokines (IL8, CCL20, CCL2) and evoking a strong in vivo antibody
response against a model epitope. More importantly, MA flagellins were fully
functional, in vitro or in vivo, in the presence of a high concentration of
neutralizing anti-flagellin STF antibodies, and STF flagellin was not inhibited
by neutralizing anti-flagellin MA antibodies. The use of active flagellins from
distinct bacteria could be a useful approach to prevent systemic neutralization
of this group of adjuvants and to facilitate the rational design of flagellin
based vaccines and/or other therapeutic treatments (against ischemia, acute renal
failure, tumors, ionizing radiations and also to improve the outcome of bone
marrow transplants).
PMID- 23155385
TI - Definition of the sigma(W) regulon of Bacillus subtilis in the absence of stress.
AB - Bacteria employ extracytoplasmic function (ECF) sigma factors for their responses
to environmental stresses. Despite intensive research, the molecular dissection
of ECF sigma factor regulons has remained a major challenge due to overlaps in
the ECF sigma factor-regulated genes and the stimuli that activate the different
ECF sigma factors. Here we have employed tiling arrays to single out the ECF
sigma(W) regulon of the Gram-positive bacterium Bacillus subtilis from the
overlapping ECF sigma(X), sigma(Y), and sigma(M) regulons. For this purpose, we
profiled the transcriptome of a B. subtilis sigW mutant under non-stress
conditions to select candidate genes that are strictly sigma(W)-regulated. Under
these conditions, sigma(W) exhibits a basal level of activity. Subsequently, we
verified the sigma(W)-dependency of candidate genes by comparing their transcript
profiles to transcriptome data obtained with the parental B. subtilis strain 168
grown under 104 different conditions, including relevant stress conditions, such
as salt shock. In addition, we investigated the transcriptomes of rasP or prsW
mutant strains that lack the proteases involved in the degradation of the
sigma(W) anti-sigma factor RsiW and subsequent activation of the sigma(W)
regulon. Taken together, our studies identify 89 genes as being strictly sigma(W)
regulated, including several genes for non-coding RNAs. The effects of rasP or
prsW mutations on the expression of sigma(W)-dependent genes were relatively
mild, which implies that sigma(W)-dependent transcription under non-stress
conditions is not strictly related to RasP and PrsW. Lastly, we show that the
pleiotropic phenotype of rasP mutant cells, which have defects in competence
development, protein secretion and membrane protein production, is not mirrored
in the transcript profile of these cells. This implies that RasP is not only
important for transcriptional regulation via sigma(W), but that this membrane
protease also exerts other important post-transcriptional regulatory functions.
PMID- 23155386
TI - Biological effects of cigarette smoke in cultured human retinal pigment
epithelial cells.
AB - The goal of the present study was to determine whether treatment with cigarette
smoke extract (CSE) induces cell loss, cellular senescence, and extracellular
matrix (ECM) synthesis in primary human retinal pigment epithelial (RPE) cells.
Primary cultured human RPE cells were exposed to 2, 4, 8, and 12% of CSE
concentration for 24 hours. Cell loss was detected by cell viability assay. Lipid
peroxidation was assessed by loss of cis-parinaric acid (PNA) fluorescence.
Senescence-associated beta-galactosidase (SA-beta-Gal) activity was detected by
histochemical staining. Expression of apolipoprotein J (Apo J), connective tissue
growth factor (CTGF), fibronectin, and laminin were examined by real-time PCR,
western blot, or ELISA experiments. The results showed that exposure of cells to
12% of CSE concentration induced cell death, while treatment of cells with 2, 4,
and 8% CSE increased lipid peroxidation. Exposure to 8% of CSE markedly increased
the number of SA-beta-Gal positive cells to up to 82%, and the mRNA expression of
Apo J, CTGF, and fibronectin by approximately 3-4 fold. Treatment with 8% of CSE
also increased the protein expression of Apo J and CTGF and the secretion of
fibronectin and laminin. Thus, treatment with CSE can induce cell loss, senescent
changes, and ECM synthesis in primary human RPE cells. It may be speculated that
cigarette smoke could be involved in cellular events in RPE cells as seen in age
related macular degeneration.
PMID- 23155387
TI - Equivalence of self- and staff-collected nasal swabs for the detection of viral
respiratory pathogens.
AB - BACKGROUND: The need for the timely collection of diagnostic biosamples during
symptomatic episodes represents a major obstacle to large-scale studies on acute
respiratory infection (ARI) epidemiology. This may be circumvented by having the
participants collect their own nasal swabs. We compared self- and staff-collected
swabs in terms of swabbing quality and detection of viral respiratory pathogens.
METHODOLOGY/PRINCIPAL FINDINGS: We conducted a prospective study among employees
of our institution during the ARI season 2010/2011 (December-March). Weekly
emails were sent to the participants (n = 84), reminding them to come to the
study center in case of new symptoms. The participants self-collected an anterior
nasal swab from one nostril, and trained study personnel collected one from the
other nostril. The participants self-collected another two swabs (one from each
nostril) on a subsequent day. Human beta-actin DNA concentration was determined
in the swabs as a quality control. Viral respiratory pathogens were detected by
multiplex RT-PCR (Seeplex RV15 kit, Seegene, Eschborn, Germany). Of 84
participants, 56 (67%) reported at least one ARI episode, 18 participants two,
and one participant three. Self-swabbing was highly accepted by the participants.
The amount of beta-actin DNA per swab was higher in the self- than in the staff
collected swabs (p = 0.008). beta-actin concentration was lower in the self-swabs
collected on day 1 than in those collected on a subsequent day (p<0.0001). A
respiratory viral pathogen was detected in 31% (23/75) of staff- and in 35%
(26/75) of self-collected swabs (p = 0.36). With both approaches, the most
frequently identified pathogens were human rhinoviruses A/B/C (12/75 swabs, 16%)
and human coronavirus OC43 (4/75 swabs, 5%). There was almost perfect agreement
between self- and staff-collected swabs in terms of pathogen detection (agreement
= 93%, kappa = 0.85, p<0.0001). CONCLUSIONS/SIGNIFICANCE: Nasal self-swabbing for
identification of viral ARI pathogens proved to be equivalent to staff-swabbing
in this population in terms of acceptance and pathogen detection.
PMID- 23155388
TI - Multi-color single particle tracking with quantum dots.
AB - Quantum dots (QDs) have long promised to revolutionize fluorescence detection to
include even applications requiring simultaneous multi-species detection at
single molecule sensitivity. Despite the early promise, the unique optical
properties of QDs have not yet been fully exploited in e. g. multiplex single
molecule sensitivity applications such as single particle tracking (SPT). In
order to fully optimize single molecule multiplex application with QDs, we have
in this work performed a comprehensive quantitative investigation of the
fluorescence intensities, fluorescence intensity fluctuations, and hydrodynamic
radii of eight types of commercially available water soluble QDs. In this study,
we show that the fluorescence intensity of CdSe core QDs increases as the
emission of the QDs shifts towards the red but that hybrid CdSe/CdTe core QDs are
less bright than the furthest red-shifted CdSe QDs. We further show that there is
only a small size advantage in using blue-shifted QDs in biological applications
because of the additional size of the water-stabilizing surface coat. Extending
previous work, we finally also show that parallel four color multicolor (MC)-SPT
with QDs is possible at an image acquisition rate of at least 25 Hz. We
demonstrate the technique by measuring the lateral dynamics of a lipid, biotin
cap-DPPE, in the cellular plasma membrane of live cells using four different
colors of QDs; QD565, QD605, QD655, and QD705 as labels.
PMID- 23155389
TI - Not all offspring are created equal: variation in larval characteristics in a
serially spawning damselfish.
AB - The way organisms allocate their resources to growth and reproduction are key
attributes differentiating life histories. Many organisms spawn multiple times in
a breeding season, but few studies have investigated the impact of serial
spawning on reproductive allocation. This study investigated whether resource
allocation was influenced by parental characteristics and prior spawning history
in a serial spawning tropical damselfish (Pomacentrus amboinensis). The offspring
attributes of isolated parents of known characteristics were monitored over a 6
week breeding period in the field. Smaller females produced larvae of longer
length and larger energy reserves at hatching. This finding is contrary to
several other studies that found larger females produce offspring of greater
quality. We found that resource allocation in the form of reproductive output was
not influenced by the number of spawning events within the breeding season, with
larger females producing the greatest number of offspring. Larval characteristics
changed as spawning progressed. There was a general decline in length of larvae
produced, with an increase in the size of the larval yolk-sac, for all females
regardless of size as spawning progressed. This trend was accentuated by the
smallest females. This change in larval characteristics may reflect a parental
ability to forecast unfavourable conditions as the season progresses or a
mechanism to ensure that some will survive no matter what conditions they
encounter. This study highlights the importance of accounting for temporal
changes in reproductive allocation in studies of reproductive trade-offs and
investigations into the importance of parental effects.
PMID- 23155390
TI - Racial bias in perceptions of others' pain.
AB - The present work provides evidence that people assume a priori that Blacks feel
less pain than do Whites. It also demonstrates that this bias is rooted in
perceptions of status and the privilege (or hardship) status confers, not race
per se. Archival data from the National Football League injury reports reveal
that, relative to injured White players, injured Black players are deemed more
likely to play in a subsequent game, possibly because people assume they feel
less pain. Experiments 1-4 show that White and Black Americans-including
registered nurses and nursing students-assume that Black people feel less pain
than do White people. Finally, Experiments 5 and 6 provide evidence that this
bias is rooted in perceptions of status, not race per se. Taken together, these
data have important implications for understanding race-related biases and
healthcare disparities.
PMID- 23155391
TI - Dysplasia-carcinoma transition specific transcripts in colonic biopsy samples.
AB - BACKGROUND: The early molecular detection of the dysplasia-carcinoma transition
may enhance the strength of diagnosis in the case of colonic biopsies. Our aims
were to identify characteristic transcript sets in order to develop diagnostic
mRNA expression patterns for objective classification of benign and malignant
colorectal diseases and to test the classificatory power of these markers on an
independent sample set. METHODOLOGY/PRINCIPAL FINDINGS: Colorectal cancer (CRC)
and adenoma specific transcript sets were identified using HGU133plus2
microarrays and 53 biopsies (22 CRC, 20 adenoma and 11 normal). Ninety-four
independent biopsies (27 CRC, 29 adenoma and 38 normal) were analyzed on
microarrays for testing the classificatory power of the discriminatory genes.
Array real-time PCR validation was done on 68 independent samples (24 CRC, 24
adenoma and 20 normal). A set of 11 transcripts (including CXCL1, CHI3L1 and
GREM1) was determined which could correctly discriminate between high-grade
dysplastic adenoma and CRC samples by 100% sensitivity and 88.9% specificity. The
discriminatory power of the marker set was proved to be high on independent
samples in both microarray and RT-PCR analyses. 95.6% of original and 94.1% of
cross-validated samples was correctly classified in discriminant analysis.
CONCLUSIONS/SIGNIFICANCE: The identified transcripts could correctly characterize
the dysplasia-carcinoma transition in biopsy samples, also on a large independent
sample set. These markers can establish the basis of gene expression based
diagnostic classification of colorectal cancer. Diagnostic RT-PCR cards can
become part of the automated routine procedure.
PMID- 23155392
TI - RAD001 enhances the potency of BEZ235 to inhibit mTOR signaling and tumor growth.
AB - The mammalian target of rapamycin (mTOR) is regulated by oncogenic growth factor
signals and plays a pivotal role in controlling cellular metabolism, growth and
survival. Everolimus (RAD001) is an allosteric mTOR inhibitor that has shown
marked efficacy in certain cancers but is unable to completely inhibit mTOR
activity. ATP-competitive mTOR inhibitors such as NVP-BEZ235 can block rapamycin
insensitive mTOR readouts and have entered clinical development as anti-cancer
agents. Here, we show the degree to which RAD001 and BEZ235 can be
synergistically combined to inhibit mTOR pathway activation, cell proliferation
and tumor growth, both in vitro and in vivo. RAD001 and BEZ235 synergized in
cancer lines representing different lineages and genetic backgrounds. Strong
synergy is seen in neuronal, renal, breast, lung, and haematopoietic cancer cells
harboring abnormalities in PTEN, VHL, LKB1, Her2, or KRAS. Critically, in the
presence of RAD001, the mTOR-4EBP1 pathway and tumorigenesis can be fully
inhibited using lower doses of BEZ235. This is relevant since RAD001 is
relatively well tolerated in patients while the toxicity profiles of ATP
competitive mTOR inhibitors are currently unknown.
PMID- 23155393
TI - The time course of activation of object shape and shape+colour representations
during memory retrieval.
AB - Little is known about the timing of activating memory for objects and their
associated perceptual properties, such as colour, and yet this is important for
theories of human cognition. We investigated the time course associated with
early cognitive processes related to the activation of object shape and object
shape+colour representations respectively, during memory retrieval as assessed by
repetition priming in an event-related potential (ERP) study. The main findings
were as follows: (1) we identified a unique early modulation of mean ERP
amplitude during the N1 that was associated with the activation of object shape
independently of colour; (2) we also found a subsequent early P2 modulation of
mean amplitude over the same electrode clusters associated with the activation of
object shape+colour representations; (3) these findings were apparent across both
familiar (i.e., correctly coloured - yellow banana) and novel (i.e., incorrectly
coloured - blue strawberry) objects; and (4) neither of the modulations of mean
ERP amplitude were evident during the P3. Together the findings delineate the
timing of object shape and colour memory systems and support the notion that
perceptual representations of object shape mediate the retrieval of temporary
shape+colour representations for familiar and novel objects.
PMID- 23155394
TI - Honeybees (Apis mellifera) learn color discriminations via differential
conditioning independent of long wavelength (green) photoreceptor modulation.
AB - BACKGROUND: Recent studies on colour discrimination suggest that experience is an
important factor in how a visual system processes spectral signals. In insects it
has been shown that differential conditioning is important for processing fine
colour discriminations. However, the visual system of many insects, including the
honeybee, has a complex set of neural pathways, in which input from the long
wavelength sensitive ('green') photoreceptor may be processed either as an
independent achromatic signal or as part of a trichromatic opponent-colour
system. Thus, a potential confound of colour learning in insects is the
possibility that modulation of the 'green' photoreceptor could underlie
observations. METHODOLOGY/PRINCIPAL FINDINGS: We tested honeybee vision using
light emitting diodes centered on 414 and 424 nm wavelengths, which limit
activation to the short-wavelength-sensitive ('UV') and medium-wavelength
sensitive ('blue') photoreceptors. The absolute irradiance spectra of stimuli was
measured and modelled at both receptor and colour processing levels, and stimuli
were then presented to the bees in a Y-maze at a large visual angle (26 degrees
), to ensure chromatic processing. Sixteen bees were trained over 50 trials,
using either appetitive differential conditioning (N = 8), or aversive-appetitive
differential conditioning (N = 8). In both cases the bees slowly learned to
discriminate between the target and distractor with significantly better accuracy
than would be expected by chance. Control experiments confirmed that changing
stimulus intensity in transfers tests does not significantly affect bee
performance, and it was possible to replicate previous findings that bees do not
learn similar colour stimuli with absolute conditioning. CONCLUSION: Our data
indicate that honeybee colour vision can be tuned to relatively small spectral
differences, independent of 'green' photoreceptor contrast and brightness cues.
We thus show that colour vision is at least partly experience dependent, and
behavioural plasticity plays an important role in how bees exploit colour
information.
PMID- 23155395
TI - Prediction of the location of the pyramidal tract in patients with thalamic or
basal ganglia tumors.
AB - BACKGROUND: Locating the pyramidal tract (PT) is difficult in patients with
thalamic or basal ganglia tumors, especially when the surrounding anatomical
structures cannot be identified using computed tomography or magnetic resonance
images. Hence, we objected to find a way to predict the location of the PT in
patients with thalamic and basal ganglia tumors METHODOLOGY/PRINCIPAL FINDINGS:
In 59 patents with thalamic or basal ganglia tumors, the PTs were constructed by
with diffusion tensor imaging (DTI)-based fiber tracking (FT). In axial slices
crossing the foramen of Monro, the tumor position was classified according to
three lines. Line 1 was vertical and crossed the vertex point of the anterior
limbs of the internal capsule. Lines 2 and line 3 were horizontal and crossed the
foramen of Monro and joint of the middle and lateral thirds of the posterior
limbs, respectively. Six (10.17%) patients were diagnosed with type 1 tumor, six
(10.17%) with type 2, seven (11.86%) with type 3a, five (8.47%) with type 3b, 17
(28.81%) with type 4a, six (10.17%) with type 4b, three (5.08%) with type 5, and
nine (15.25%) with type 6. In type 1 tumors, the PTs were located at the 12
o'clock position of the tumor, type 2 at six o'clock, type 3a between nine and 12
o'clock, type 3 between six and nine o'clock, type 4a between 12 and three
o'clock, type 4b at three o'clock, type 5 between six and nine o'clock, and type
6 between three and six o'clock. CONCLUSIONS/SIGNIFICANCE: The position of the PT
relative to the tumor could be determined according to the tumor location. These
results could prove helpful in determining the location of the PT preoperatively.
PMID- 23155397
TI - Multi-state proteins: approach allowing experimental determination of the
formation order of structure elements in the green fluorescent protein.
AB - The most complex problem in studying multi-state protein folding is the
determination of the sequence of formation of protein intermediate states. A far
more complex issue is to determine at what stages of protein folding its various
parts (secondary structure elements) develop. The structure and properties of
different intermediate states depend in particular on these parts. An
experimental approach, named MU-analysis, which allows understanding the order of
formation of structural elements upon folding of a multi-state protein was used
in this study. In this approach the same elements of the protein secondary
structure are "tested" by substitutions of single hydrophobic amino acids and by
incorporation of cysteine bridges. Single substitutions of hydrophobic amino
acids contribute to yielding information on the late stages of protein folding
while incorporation of ss-bridges allows obtaining data on the initial stages of
folding. As a result of such an MU-analysis, we have determined the order of
formation of beta-hairpins upon folding of the green fluorescent protein.
PMID- 23155396
TI - Epigenetic and genetic factors predict women's salivary cortisol following a
threat to the social self.
AB - Evidence suggests that the reactivity of the Hypothalamus-Pituitary-Adrenal axis
(HPAA) is modulated by both genetic and environmental variables. Of special
interest are the underlying molecular mechanisms driving gender differences to
psychosocial stressors. Epigenetic mechanisms that sculpt the genome are ideal
candidates for mediating the effects of signals on the HPAA. In the current
study, we analyzed by pyrosequencing, bisulfite-treated buccal DNA from male and
female university students who participated in the Trier Social Stress Test
(TSST). A linear regression model was used to ascertain the effects of sex, CpG
methylation and genes on stress response. Total cortisol output (area under the
curve, AUC) was significantly predicted by glucocorticoid receptor (NR3C1) exon
1F methylation (averaged across 39 CpG sites) solely in female subjects. A single
CpG site located in the exon 1F noncanonical nerve growth factor-inducible
protein A (NGFI-A) transcription factor was a highly significant predictor of AUC
in female subjects. Additionally, variations in the estrogen receptor alpha
(ESR1) and the serotonin transporter promoter (5-HTTLPR) genes were independent
additive predictors of AUC. The full model accounted for half of the variance
(50.06%) in total cortisol output. Notably, this is the first demonstration that
epigenetic changes at the GR exon 1F correlate with HPAA reactivity. These
findings have important implications for understanding the molecular mechanisms
underlying gender differences in stress-related disorders and underscore the
unique value of modeling both epigenetic and genetic information in conferring
vulnerability to stress.
PMID- 23155398
TI - Increased adipogenesis in cultured embryonic chondrocytes and in adult bone
marrow of dominant negative Erg transgenic mice.
AB - In monolayer culture, primary articular chondrocytes have an intrinsic tendency
to lose their phenotype during expansion. The molecular events underlying this
chondrocyte dedifferentiation are still largely unknown. Several transcription
factors are important for chondrocyte differentiation. The Ets transcription
factor family may be involved in skeletal development. One family member, the Erg
gene, is mainly expressed during cartilage formation. To further investigate the
potential role of Erg in the maintenance of the chondrocyte phenotype, we
isolated and cultured chondrocytes from the rib cartilage of embryos of
transgenic mice that express a dominant negative form of Erg (DN-Erg) during
cartilage formation. DN-Erg expression in chondrocytes cultured for up to 20 days
did not affect the early dedifferentiation usually observed in cultured
chondrocytes. However, lipid droplets accumulated in DN-Erg chondrocytes,
suggesting adipocyte emergence. Transcriptomic analysis using a DNA microarray,
validated by quantitative RT-PCR, revealed strong differential gene expression,
with a decrease in chondrogenesis-related markers and an increase in adipogenesis
related gene expression in cultured DN-Erg chondrocytes. These results indicate
that Erg is involved in either maintaining the chondrogenic phenotype in vitro or
in cell fate orientation. Along with the in vitro studies, we compared adipocyte
presence in wild-type and transgenic mice skeletons. Histological investigations
revealed an increase in the number of adipocytes in the bone marrow of adult DN
Erg mice even though no adipocytes were detected in embryonic cartilage or bone.
These findings suggest that the Ets transcription factor family may contribute to
the homeostatic balance in skeleton cell plasticity.
PMID- 23155399
TI - A nice day for an infection? Weather conditions and social contact patterns
relevant to influenza transmission.
AB - Although there is no doubt that significant morbidity and mortality occur during
annual influenza epidemics, the role of contextual circumstances, which catalyze
seasonal influenza transmission, remains unclear. Weather conditions are believed
to affect virus survival, efficiency of transmission and host immunity, but
seasonality may also be driven by a tendency of people to congregate indoors
during periods of bad weather. To test this hypothesis, we combined data from a
social contact survey in Belgium with local weather data. In the absence of a
previous in-depth weather impact analysis of social contact patterns, we explored
the possibilities and identified pitfalls. We found general dominance of day-type
(weekend, holiday, working day) over weather conditions, but nonetheless observed
an increase in long duration contacts ([Formula: see text]1 hour) on regular
workdays with low temperatures, almost no precipitation and low absolute humidity
of the air. Interestingly, these conditions are often assumed to be beneficial
for virus survival and transmission. Further research is needed to establish the
impact of the weather on social contacts. We recommend that future studies sample
over a broad spectrum of weather conditions and day types and include a
sufficiently large proportion of holiday periods and weekends.
PMID- 23155400
TI - Rural to urban migration is an unforeseen impact of development intervention in
Ethiopia.
AB - Rural development initiatives across the developing world are designed to improve
community well-being and livelihoods. However they may also have unforeseen
consequences, in some cases placing further demands on stretched public services.
In this paper we use data from a longitudinal study of five Ethiopian villages to
investigate the impact of a recent rural development initiative, installing
village-level water taps, on rural to urban migration of young adults. Our
previous research has identified that tap stands dramatically reduced child
mortality, but were also associated with increased fertility. We demonstrate that
the installation of taps is associated with increased rural-urban migration of
young adults (15-30 years) over a 15 year period (15.5% migrate out, n = 1912
from 1280 rural households). Young adults with access to this rural development
intervention had three times the relative risk of migrating to urban centres
compared to those without the development. We also identify that family dynamics,
specifically sibling competition for limited household resources (e.g. food,
heritable land and marriage opportunities), are key to understanding the timing
of out-migration. Birth of a younger sibling doubled the odds of out-migration
and starting married life reduced it. Rural out-migration appears to be a
response to increasing rural resource scarcity, principally competition for
agricultural land. Strategies for livelihood diversification include education
and off-farm casual wage-labour. However, jobs and services are limited in urban
centres, few migrants send large cash remittances back to their families, and
most return to their villages within one year without advanced qualifications.
One benefit for returning migrants may be through enhanced social prestige and
mate-acquisition on return to rural areas. These findings have wide implications
for current understanding of the processes which initiate rural-to-urban
migration and transitions to low fertility, as well as for the design and
implementation of development intervention across the rural and urban developing
world.
PMID- 23155401
TI - Photoinduced disaggregation of TiO2 nanoparticles enables transdermal
penetration.
AB - Under many aqueous conditions, metal oxide nanoparticles attract other
nanoparticles and grow into fractal aggregates as the result of a balance between
electrostatic and Van Der Waals interactions. Although particle coagulation has
been studied for over a century, the effect of light on the state of aggregation
is not well understood. Since nanoparticle mobility and toxicity have been shown
to be a function of aggregate size, and generally increase as size decreases,
photo-induced disaggregation may have significant effects. We show that ambient
light and other light sources can partially disaggregate nanoparticles from the
aggregates and increase the dermal transport of nanoparticles, such that small
nanoparticle clusters can readily diffuse into and through the dermal profile,
likely via the interstitial spaces. The discovery of photoinduced disaggregation
presents a new phenomenon that has not been previously reported or considered in
coagulation theory or transdermal toxicological paradigms. Our results show that
after just a few minutes of light, the hydrodynamic diameter of TiO(2) aggregates
is reduced from ~280 nm to ~230 nm. We exposed pigskin to the nanoparticle
suspension and found 200 mg kg(-1) of TiO(2) for skin that was exposed to
nanoparticles in the presence of natural sunlight and only 75 mg kg(-1) for skin
exposed to dark conditions, indicating the influence of light on NP penetration.
These results suggest that photoinduced disaggregation may have important health
implications.
PMID- 23155402
TI - Pathways to age of onset of heroin use: a structural model approach exploring the
relationship of the COMT gene, impulsivity and childhood trauma.
AB - BACKGROUND: The interaction of the association of dopamine genes, impulsivity and
childhood trauma with substance abuse remains unclear. OBJECTIVES: To clarify the
impacts and the interactions of the Catechol -O-methyltransferase (COMT) gene,
impulsivity and childhood trauma on the age of onset of heroin use among heroin
dependent patients in China. METHODS: 202 male and 248 female inpatients who meet
DSM-IV criteria of heroin dependence were enrolled. Impulsivity and childhood
trauma were measured using BIS-11 (Barratt Impulsiveness Scale-11) and ETISR-SF
(Early Trauma Inventory Self Report-Short Form). The single nucleotide
polymorphism (SNP) rs737866 on the COMT gene-which has previously been associated
with heroin abuse, was genotyped using a DNA sequence detection system.
Structural equations model was used to assess the interaction paths between these
factors and the age of onset of heroin use. PRINCIPAL FINDINGS: Chi-square test
indicated the individuals with TT allele have earlier age of onset of heroin use
than those with CT or CC allele. In the correlation analysis, the severity of
childhood trauma was positively correlated to impulsive score, but both of them
were negatively related to the age of onset of heroin use. In structure equation
model, both the COMT gene and childhood trauma had impacts on the age of onset of
heroin use directly or via impulsive personality. CONCLUSIONS: Our findings
indicated that the COMT gene, impulsive personality traits and childhood trauma
experience were interacted to impact the age of onset of heroin use, which play a
critical role in the development of heroin dependence. The impact of
environmental factor was greater than the COMT gene in the development of heroin
dependence.
PMID- 23155403
TI - Identification of a plant viral RNA genome in the nucleus.
AB - Viruses contain either DNA or RNA as genomes. DNA viruses replicate within
nucleus, while most RNA viruses, especially (+)-sense single-stranded RNA,
replicate and are present within cytoplasm. We proposed a new thought that is
contrary to the common notion that (+)-sense single-stranded RNA viruses are
present only in the cytoplasm. In this study, we question whether the genome of a
plant RNA virus (non-retroviral) is present in the nucleus of infected cells?
Hibiscus chlorotic ringspot virus (HCRSV) RNA was detected in the nucleus of
infected cells, as shown by fluorescent in situ hybridization. Western blot using
anti-histone 3 and anti-phosphoenolpyruvate carboxylase showed that nuclei were
highly purified from mock and HCRSV-infected kenaf (Hibiscus cannabilis L.)
leaves, respectively. The p23 and HCRSV coat protein (CP) coding regions were
both amplified from total RNA extracted from isolated nuclei. Viral RNA in the
nucleus may be used to generate viral microRNAs (vir-miRNAs), as five putative
vir-miRNAs were predicted from HCRSV using the vir-miRNAs prediction database.
The vir-miRNA (hcrsv-miR-H1-5p) was detected using TaqMan(r) stem-loop real-time
PCR, and by northern blot using DIG-end labeled probe in HCRSV-infected kenaf
leaves. Finally, a novel nuclear localization signal (NLS) was discovered in p23
of HCRSV. The NLS interacts with importin alpha and facilitates viral RNA genome
to enter nucleus. We demonstrate the presence of a (+)-sense single-stranded
viral RNA within nucleus.
PMID- 23155404
TI - Mos1-mediated transgenesis to probe consequences of single gene mutations in
variation-rich isolates of Caenorhabditis elegans.
AB - Caenorhabditis elegans, especially the N2 isolate, is an invaluable biological
model system. Numerous additional natural C. elegans isolates have been shown to
have unexpected genotypic and phenotypic variations which has encouraged
researchers to use next generation sequencing methodology to develop a more
complete picture of genotypic variations among the isolates. To understand the
phenotypic effects of a genomic variation (GV) on a single gene, in a variation
rich genetic background, one should analyze that particular GV in a well
understood genetic background. In C. elegans, the analysis is usually done in N2,
which requires extensive crossing to bring in the GV. This can be a very time
consuming procedure thus it is important to establish a fast and efficient
approach to test the effect of GVs from different isolates in N2. Here we use a
Mos1-mediated single-copy insertion (MosSCI) method for phenotypic assessments of
GVs from the variation-rich Hawaiian strain CB4856 in N2. Specifically, we
investigate effects of variations identified in the CB4856 strain on tac-1 which
is an essential gene that is necessary for mitotic spindle elongation and
pronuclear migration. We show the usefulness of the MosSCI method by using EU1004
tac-1(or402) as a control. or402 is a temperature sensitive lethal allele within
a well-conserved TACC domain (transforming acidic coiled-coil) that results in a
leucine to phenylalanine change at amino acid 229. CB4856 contains a variation
that affects the second exon of tac-1 causing a cysteine to tryptophan change at
amino acid 94 also within the TACC domain. Using the MosSCI method, we analyze
tac-1 from CB4856 in the N2 background and demonstrate that the C94W change,
albeit significant, does not cause any obvious decrease in viability. This MosSCI
method has proven to be a rapid and efficient way to analyze GVs.
PMID- 23155405
TI - Biomarkers of Plasmodium falciparum infection during pregnancy in women living in
northeastern Tanzania.
AB - In pregnant women, Plasmodium falciparum infections are an important cause of
maternal morbidity as well as fetal and neonatal mortality. Erythrocytes infected
by these malaria-causing parasites accumulate through adhesive interactions in
placental intervillous spaces, thus evading detection in peripheral blood smears.
Sequestered infected erythrocytes induce inflammation, offering the possibility
of detecting inflammatory mediators in peripheral blood that could act as
biomarkers of placental infection. In a longitudinal, prospective study in
Tanzania, we quantified a range of different cytokines, chemokines and angiogenic
factors in peripheral plasma samples, taken on multiple sequential occasions
during pregnancy up to and including delivery, from P. falciparum-infected women
and matched uninfected controls. The results show that during healthy, uninfected
pregnancies the levels of most of the panel of molecules we measured were largely
unchanged except at delivery. In women with P. falciparum, however, both
comparative and longitudinal assessments consistently showed that the levels of
IL-10 and IP-10 increased significantly whilst that of RANTES decreased
significantly, regardless of gestational age at the time the infection was
detected. ROC curve analysis indicated that a combination of increased IL-10 and
IP-10 levels and decreased RANTES levels might be predictive of P. falciparum
infections. In conclusion, our data suggest that host biomarkers in peripheral
blood may represent useful diagnostic markers of P. falciparum infection during
pregnancy, but placental histology results would need to be included to verify
these findings.
PMID- 23155406
TI - Plac8 is required for white adipocyte differentiation in vitro and cell number
control in vivo.
AB - Plac8 belongs to an evolutionary conserved family of proteins, mostly abundant in
plants where they control fruit weight through regulation of cell number. In
mice, Plac8 is expressed both in white and brown adipose tissues and we
previously showed that Plac8(-/-) mice develop late-onset obesity, with abnormal
brown fat differentiation and reduced thermogenic capacity. We also showed that
in brown adipocytes, Plac8 is an upstream regulator of C/EBPbeta expression.
Here, we first assessed the role of Plac8 in white adipogenesis in vitro. We show
that Plac8 is induced early after induction of 3T3-L1 adipocytes differentiation,
a process that is prevented by Plac8 knockdown; similarly, embryonic fibroblasts
obtained from Plac8 knockout mice failed to form adipocytes upon stimulation of
differentiation. Knockdown of Plac8 in 3T3-L1 was associated with reduced
expression of C/EBPbeta, Krox20, and Klf4, early regulators of the white
adipogenic program, and we show that Plac8 could transactivate the C/EBPbeta
promoter. In vivo, we show that absence of Plac8 led to increased white fat mass
with enlarged adipocytes but reduced total number of adipocytes. Finally, even
though Plac8(-/-) mice showed impaired thermogenesis due to brown fat
dysfunction, this was not associated with changes in glycemia or plasma free
fatty acid and triglyceride levels. Collectively, these data indicate that Plac8
is an upstream regulator of C/EBPbeta required for adipogenesis in vitro.
However, in vivo, Plac8 is dispensable for the differentiation of white
adipocytes with preserved fat storage capacity but is required for normal fat
cell number regulation.
PMID- 23155407
TI - Chronic temporal lobe epilepsy is associated with enhanced Alzheimer-like
neuropathology in 3*Tg-AD mice.
AB - The comorbidity between epilepsy and Alzheimer's disease (AD) is a topic of
growing interest. Senile plaques and tauopathy are found in epileptic human
temporal lobe structures, and individuals with AD have an increased incidence of
spontaneous seizures. However, why and how epilepsy is associated with enhanced
AD-like pathology remains unknown. We have recently shown beta-secretase-1
(BACE1) elevation associated with aberrant limbic axonal sprouting in epileptic
CD1 mice. Here we sought to explore whether BACE1 upregulation affected the
development of Alzheimer-type neuropathology in mice expressing mutant human APP,
presenilin and tau proteins, the triple transgenic model of AD (3*Tg-AD). 3*Tg-AD
mice were treated with pilocarpine or saline (i.p.) at 6-8 months of age.
Immunoreactivity (IR) for BACE1, beta-amyloid (Abeta) and phosphorylated tau (p
tau) was subsequently examined at 9, 11 or 14 months of age. Recurrent convulsive
seizures, as well as mossy fiber sprouting and neuronal death in the hippocampus
and limbic cortex, were observed in all epileptic mice. Neuritic plaques composed
of BACE1-labeled swollen/sprouting axons and extracellular AbetaIR were seen in
the hippocampal formation, amygdala and piriform cortices of 9 month-old
epileptic, but not control, 3*Tg-AD mice. Densities of plaque-associated BACE1
and AbetaIR were elevated in epileptic versus control mice at 11 and 14 months of
age. p-Tau IR was increased in dentate granule cells and mossy fibers in
epileptic mice relative to controls at all time points examined. Thus,
pilocarpine-induced chronic epilepsy was associated with accelerated and enhanced
neuritic plaque formation and altered intraneuronal p-tau expression in temporal
lobe structures in 3*Tg-AD mice, with these pathologies occurring in regions
showing neuronal death and axonal dystrophy.
PMID- 23155408
TI - The temporal dynamics of early visual cortex involvement in behavioral priming.
AB - Transcranial magnetic stimulation (TMS) allows for non-invasive interference with
ongoing neural processing. Applied in a chronometric design over early visual
cortex (EVC), TMS has proved valuable in indicating at which particular time
point EVC must remain unperturbed for (conscious) vision to be established. In
the current study, we set out to examine the effect of EVC TMS across a broad
range of time points, both before (pre-stimulus) and after (post-stimulus) the
onset of symbolic visual stimuli. Behavioral priming studies have shown that the
behavioral impact of a visual stimulus can be independent from its conscious
perception, suggesting two independent neural signatures. To assess whether TMS
induced suppression of visual awareness can be dissociated from behavioral
priming in the temporal domain, we thus implemented three different measures of
visual processing, namely performance on a standard visual discrimination task, a
subjective rating of stimulus visibility, and a visual priming task. To control
for non-neural TMS effects, we performed electrooculographical recordings,
placebo TMS (sham), and control site TMS (vertex). Our results suggest that, when
considering the appropriate control data, the temporal pattern of EVC TMS
disruption on visual discrimination, subjective awareness and behavioral priming
are not dissociable. Instead, TMS to EVC disrupts visual perception holistically,
both when applied before and after the onset of a visual stimulus. The current
findings are discussed in light of their implications on models of visual
awareness and (subliminal) priming.
PMID- 23155409
TI - Food webs in the human body: linking ecological theory to viral dynamics.
AB - The dynamics of in-host infections are central to predicting the progression of
natural infections and the effectiveness of drugs or vaccines, however, they are
not well understood. Here, we apply food web theory to in-host disease networks
of the human body that are structured similarly to food web models that treat
both predation and competition simultaneously. We show that in-host trade-offs,
an under-studied aspect of disease ecology, are fundamental to understanding the
outcomes of competing viral strains under differential immune responses. Further,
and importantly, our analysis shows that the outcome of competition between
virulent and non-virulent strains can be highly contingent on the abiotic
conditions prevailing in the human body. These results suggest the alarming idea
that even subtle behavioral changes that alter the human body (e.g. weight gain,
smoking) may switch the environmental conditions in a manner that suddenly allows
a virulent strain to dominate and replace less virulent strains. These ecological
results therefore cast new light on the control of disease in the human body, and
highlight the importance of longitudinal empirical studies across host variation
gradients, as well as, of studies focused on delineating life history trade-offs
within hosts.
PMID- 23155410
TI - AtaA, a new member of the trimeric autotransporter adhesins from Acinetobacter
sp. Tol 5 mediating high adhesiveness to various abiotic surfaces.
AB - Acinetobacter sp. Tol 5 exhibits an autoagglutinating nature and noteworthy
adhesiveness to various abiotic surfaces from hydrophobic plastics to hydrophilic
glass and stainless steel. Although previous studies have suggested that
bacterionanofibers on Tol 5 cells are involved in the adhesive phenotype of Tol
5, the fiber that directly mediates Tol 5 adhesion has remained unknown. Here, we
present a new member of trimeric autotransporter adhesins designated AtaA, which
we discovered by analyzing a less adhesive mutant of Tol 5, T1, obtained by
transposon mutagenesis. AtaA forms thinner and shorter nanofibers than fimbriae
on Tol 5 cells. We performed target disruption of ataA by allelic marker
exchange, and the resulting DeltaataA strain was complemented with ataA on the
Escherichia coli-Acinetobacter shuttle vector, which was newly constructed. These
results proved that AtaA is essential for Tol 5's autoagglutinating nature and
high adhesiveness to surfaces of various materials. In addition, the adhesiveness
to solid surfaces mediated by AtaA is notably higher than that mediated by YadA
of Yersinia enterocolitica WA-314. Moreover, and importantly, these
characteristics can be conferred to the non-adhesive, non-agglutinating bacterium
Acinetobacter sp. ADP1 in trans by transformation with ataA, with expected
applications to microbial immobilization.
PMID- 23155411
TI - HERVs expression in Autism Spectrum Disorders.
AB - BACKGROUND: Autistic Spectrum Disorder (ASD) is a heterogeneous
neurodevelopmental disorder, resulting from complex interactions among genetic,
genomic and environmental factors. Here we have studied the expression of Human
Endogenous Retroviruses (HERVs), non-coding DNA elements with potential
regulatory functions, and have tested their possible implication in autism.
METHODS: The presence of retroviral mRNAs from four HERV families (E, H, K and
W), widely implicated in complex diseases, was evaluated in peripheral blood
mononuclear cells (PBMCs) from ASD patients and healthy controls (HCs) by
qualitative RT-PCR. We also analyzed the expression of the env sequence from HERV
H, HERV-W and HERV-K families in PBMCs at the time of sampling and after
stimulation in culture, in both ASD and HC groups, by quantitative Real-time PCR.
Differences between groups were evaluated using statistical methods. RESULTS: The
percentage of HERV-H and HERV-W positive samples was higher among ASD patients
compared to HCs, while HERV-K was similarly represented and HERV-E virtually
absent in both groups. The quantitative evaluation shows that HERV-H and HERV-W
are differentially expressed in the two groups, with HERV-H being more abundantly
expressed and, conversely, HERV-W, having lower abundance, in PBMCs from ASDs
compared to healthy controls. PMBCs from ASDs also showed an increased potential
to up-regulate HERV-H expression upon stimulation in culture, unlike HCs.
Furthermore we report a negative correlation between expression levels of HERV-H
and age among ASD patients and a statistically significant higher expression in
ASD patients with Severe score in Communication and Motor Psychoeducational
Profile-3. CONCLUSIONS: Specific HERV families have a distinctive expression
profile in ASD patients compared to HCs. We propose that HERV-H expression be
explored in larger samples of individuals with autism spectrum in order to
determine its utility as a novel biological trait of this complex disorder.
PMID- 23155412
TI - Utility of the trnH-psbA intergenic spacer region and its combinations as plant
DNA barcodes: a meta-analysis.
AB - BACKGROUND: The trnH-psbA intergenic spacer region has been used in many DNA
barcoding studies. However, a comprehensive evaluation with rigorous sequence
preprocessing and statistical testing on the utility of trnH-psbA and its
combinations as DNA barcodes is lacking. METHODOLOGY/PRINCIPAL FINDINGS:
Sequences were searched from GenBank for a meta-analysis on the usefulness of
trnH-psbA and its combinations as DNA barcodes. After preprocessing, we
constructed full and matching data sets that contained 17 983 trnH-psbA sequences
and 2190 sets of trnH-psbA, matK, rbcL, and ITS2 sequences from the same sample,
repectively. These datasets were used to analyze the ability of trnH-psbA and its
combinations to discriminate species by the BLAST and BLAST+P methods. The
Fisher's exact test was used to evaluate the significance of performance
differences. For the full data set, the identification success rates of trnH-psbA
exceeded 70% in 18 families and 12 genera, respectively. For the matching data
set, the identification rates of trnH-psbA were significantly higher than those
of the other loci in two families and four genera. Similarly, the identification
rates of trnH-psbA+ITS2 were significantly higher than those of matK+rbcL in 18
families and 21 genera. CONCLUSION/SIGNIFICANE: This study provides valuable
information on the higher utility of trnH-psbA and its combinations. We found
that trnH-psbA+ITS2 combination performs better or equally well compared with
other combinations in most taxonomic groups investigated. This information will
guide the optimal usage of trnH-psbA and its combinations for species
identification.
PMID- 23155413
TI - Socio-economic and health access determinants of breast and cervical cancer
screening in low-income countries: analysis of the World Health Survey.
AB - BACKGROUND: Breast and Cervical cancer are the two most common cancers among
women in developing countries. Regular screening is the most effective way of
ensuring that these cancers are detected at early stages; however few studies
have assessed factors that predict cancer screening in developing countries.
PURPOSE: To assess the influence of household socio-economic status (SES),
healthcare access and country level characteristics on breast and cervical cancer
screening among women in developing countries. METHODS: Women ages 18-69 years
(cervical cancer screening) and 40-69 years (breast cancer screening) from 15
developing countries who participated in the 2003 World Health Survey provided
data for this study. Household SES and healthcare access was assessed based on
self-reported survey responses. SAS survey procedures (SAS, Version 9.2) were
used to assess determinants of breast and cervical cancer screening in separate
models. RESULTS: 4.1% of women ages 18-69 years had received cervical cancer
screening in the past three years, while only 2.2% of women ages 40-69 years had
received breast cancer screening in the past 5 years in developing countries.
Cancer screening rates varied by country; cervical cancer screening ranged from
1.1% in Bangladesh to 57.6% in Congo and breast cancer screening ranged from 0%
in Mali to 26% in Congo. Significant determinants of cancer screening were
household SES, rural residence, country health expenditure (as a percent of GDP)
as well as healthcare access. DISCUSSION: A lot more needs to be done to improve
screening rates for breast and cervical cancer in developing countries, such as
increasing health expenditure (especially in rural areas), applying the increased
funds towards the provision of more, better educated health providers as well as
improved infrastructure.
PMID- 23155415
TI - Dysregulation of IRP1-mediated iron metabolism causes gamma ray-specific
radioresistance in leukemia cells.
AB - Iron is required for nearly all organisms, playing important roles in oxygen
transport and many enzymatic reactions. Excess iron, however, can be cytotoxic.
Emerging evidence suggests that radioresistance can be achieved in lower
organisms by the protection of proteins, but not DNA, immediately following
ionizing radiation (IR) exposure, allowing for improved DNA repair. One potential
mechanism for protein protection is controlling and limiting the amount of free
iron in cells, as has been demonstrated in the extremophile Deinococcus
Radiodurans, reducing the potential for oxidative damage to proteins during
exposure to IR. We found that iron regulatory protein 1 (IRP1) expression was
markedly reduced in human myeloid leukemia HL60 cells resistant to low linear
energy transfer (LET) gamma rays, but not to high LET alpha particles. Stable
knockdown of IRP1 by short-hairpin RNA (shRNA) interference in radiosensitive
parental cells led to radioresistance to low LET IR, reduced intracellular Fenton
chemistry, reduced protein oxidation, and more rapid DNA double-strand break
(DSB) repair. The mechanism of radioresistance appeared to be related to
attenuated free radical-mediated cell death. Control of intracellular iron by
IRPs may be a novel radioresistance mechanism in mammalian cells.
PMID- 23155416
TI - Liking food less: the impact of social influence on food liking evaluations in
female students.
AB - Social factors are known to influence food intake and choice. However, whether
social influence acts on evaluations of food and drink liking has not been
studied. Across two studies, we tested whether leading a participant to believe
that other people do not like a food affects food liking evaluations. In Study 1,
we exposed participants to social normative information suggesting a) that an in
group disliked orange juice, b) that an out-group disliked orange juice or c)
that an in-group were neutral about orange juice. We then examined how much
participants believed they liked orange juice. In Study 2, participants consumed
a snack food before being led to believe that two previous participants had also
eaten the food and either disliked or quite liked it. We asked participants to
rate how much they had enjoyed eating the snack food. Across both studies, social
influence was observed, as underlined by decreases in liking evaluations. In
Study 1, beliefs about liking were only influenced by social normative
information when the norm was expressed by an in-group. In Study 2, exposure to
others' accounts of a negative experience with a food decreased evaluated liking
of the recent consumption experience. These results suggest that social influence
can act upon food liking evaluations.
PMID- 23155414
TI - Association of genetic loci with sleep apnea in European Americans and African
Americans: the Candidate Gene Association Resource (CARe).
AB - Although obstructive sleep apnea (OSA) is known to have a strong familial basis,
no genetic polymorphisms influencing apnea risk have been identified in cross
cohort analyses. We utilized the National Heart, Lung, and Blood Institute
(NHLBI) Candidate Gene Association Resource (CARe) to identify sleep apnea
susceptibility loci. Using a panel of 46,449 polymorphisms from roughly 2,100
candidate genes on a customized Illumina iSelect chip, we tested for association
with the apnea hypopnea index (AHI) as well as moderate to severe OSA (AHI>=15)
in 3,551 participants of the Cleveland Family Study and two cohorts participating
in the Sleep Heart Health Study.Among 647 African-Americans, rs11126184 in the
pleckstrin (PLEK) gene was associated with OSA while rs7030789 in the
lysophosphatidic acid receptor 1 (LPAR1) gene was associated with AHI using a
chip-wide significance threshold of p-value<2*10(-6). Among 2,904 individuals of
European ancestry, rs1409986 in the prostaglandin E2 receptor (PTGER3) gene was
significantly associated with OSA. Consistency of effects between rs7030789 and
rs1409986 in LPAR1 and PTGER3 and apnea phenotypes were observed in independent
clinic-based cohorts.Novel genetic loci for apnea phenotypes were identified
through the use of customized gene chips and meta-analyses of cohort data with
replication in clinic-based samples. The identified SNPs all lie in genes
associated with inflammation suggesting inflammation may play a role in OSA
pathogenesis.
PMID- 23155417
TI - Evaluation of forest recovery over time and space using permanent plots monitored
over 30 years in a Jamaican montane rain forest.
AB - Conservation of tropical forest biodiversity increasingly depends on its recovery
following severe human disturbance. Our ability to measure recovery using current
similarity indices suffers from two limitations: different sized individuals are
treated as equal, and the indices are proportionate (a community with twice the
individuals of every species as compared with the reference community would be
assessed as identical). We define an alternative recovery index for trees - the
Tanner index, as the mean of the quantitative Bray-Curtis similarity indices of
species composition for stem density and for basal area. We used the new index to
compare the original (pre-gap) and post-gap composition of five experimental gap
plots (each 90-100 m(2)) and four control plots over 24-35 years in the Blue
Mountains of Jamaica. After 24-35 years, these small gaps surrounded by
undisturbed forest had recovered 68% of the sum of per species stem density and
29% of the sum of per species basal area, a recovery index of 47%. Four endemic
species were especially reduced in density and basal area. With the incorporation
of basal area and stem density, our index reduces over-estimations of forest
recovery obtained using existing similarity indices (by 24%-41%), and thus yields
more accurate estimates of forest conservation status. Finally, our study
indicates that the two kinds of comparisons: 1) over time between pre-gap and
post-gap composition and 2) over space between gap plots and spatial controls
(space-for-time substitution) yield broadly similar results, which supports the
value of using space-for-time substitutions in studying forest recovery, at least
in this tropical montane forest.
PMID- 23155419
TI - Exome analysis of two limb-girdle muscular dystrophy families: mutations
identified and challenges encountered.
AB - The molecular diagnosis of muscle disorders is challenging: genetic heterogeneity
(>100 causal genes for skeletal and cardiac muscle disease) precludes exhaustive
clinical testing, prioritizing sequencing of specific genes is difficult due to
the similarity of clinical presentation, and the number of variants returned
through exome sequencing can make the identification of the disease-causing
variant difficult. We have filtered variants found through exome sequencing by
prioritizing variants in genes known to be involved in muscle disease while
examining the quality and depth of coverage of those genes. We ascertained two
families with autosomal dominant limb-girdle muscular dystrophy of unknown
etiology. To identify the causal mutations in these families, we performed exome
sequencing on five affected individuals using the Agilent SureSelect Human All
Exon 50 Mb kit and the Illumina HiSeq 2000 (2*100 bp). We identified causative
mutations in desmin (IVS3+3A>G) and filamin C (p.W2710X), and augmented the
phenotype data for individuals with muscular dystrophy due to these mutations. We
also discuss challenges encountered due to depth of coverage variability at
specific sites and the annotation of a functionally proven splice site variant as
an intronic variant.
PMID- 23155418
TI - Cell-type specific expression of the vasopressin gene analyzed by AAV mediated
gene delivery of promoter deletion constructs into the rat SON in vivo.
AB - The magnocellular neurons (MCNs) in the supraoptic nucleus (SON) of the
hypothalamus selectively express either oxytocin (Oxt) or vasopressin (Avp)
neuropeptide genes. In this paper we examine the cis-regulatory domains in the
Avp gene promoter that are responsible for its cell-type specific expression. AAV
vectors that contain various Avp gene promoter deletion constructs using EGFP as
the reporter were stereotaxically injected into the rat SON. Two weeks following
the injection immunohistochemical assays of EGFP expression from these constructs
were done to determine whether the expressed EGFP reporter co-localizes with
either the Oxt- or Avp-immunoreactivity in the MCNs. The results identify three
major enhancer domains located at -2.0 to -1.5 kbp, -1.5 to -950 bp, and -950 to
543 bp in the Avp gene promoter that regulate the expression in Avp MCNs. The
results also show that cell-type specific expression in Avp MCNs is maintained in
constructs containing at least 288 bp of the promoter region upstream of the
transcription start site, but this specificity is lost at 116 bp and below. Based
on these data, we hypothesize that the -288 bp to -116 bp domain contains an Avp
MCN specific activator and a possible repressor that inhibits expression in Oxt
MCNs, thereby leading to the cell-type specific expression of the Avp gene only
in the Avp-MCNs.
PMID- 23155420
TI - Cross regulation of sirtuin 1, AMPK, and PPARgamma in conjugated linoleic acid
treated adipocytes.
AB - Trans-10, cis-12 conjugated linoleic acid (t10c12 CLA) reduces triglyceride (TG)
levels in adipocytes through multiple pathways, with AMP-activated protein kinase
(AMPK) generally facilitating, and peroxisome proliferator-activated receptor
gamma (PPARgamma) generally opposing these reductions. Sirtuin 1 (SIRT1), a
histone/protein deacetylase that affects energy homeostasis, often functions
coordinately with AMPK, and is capable of binding to PPARgamma, thereby
inhibiting its activity. This study investigated the role of SIRT1 in the
response of 3T3-L1 adipocytes to t10c12 CLA by testing the following hypotheses:
1) SIRT1 is functionally required for robust TG reduction; and 2) SIRT1, AMPK,
and PPARgamma cross regulate each other. These experiments were performed by
using activators, inhibitors, or siRNA knockdowns that affected these pathways in
t10c12 CLA-treated 3T3-L1 adipocytes. Inhibition of SIRT1 amounts or activity
using siRNA, sirtinol, nicotinamide, or etomoxir attenuated the amount of TG
loss, while SIRT1 activator SRT1720 increased the TG loss. SRT1720 increased AMPK
activity while sirtuin-specific inhibitors decreased AMPK activity. Reciprocally,
an AMPK inhibitor reduced SIRT1 activity. Treatment with t10c12 CLA increased
PPARgamma phosphorylation in an AMPK-dependent manner and increased the amount of
PPARgamma bound to SIRT1. Reciprocally, a PPARgamma agonist attenuated AMPK and
SIRT1 activity levels. These results indicated SIRT1 increased TG loss and that
cross regulation between SIRT1, AMPK, and PPARgamma occurred in 3T3-L1 adipocytes
treated with t10c12 CLA.
PMID- 23155421
TI - Isolated Toll-like receptor transmembrane domains are capable of oligomerization.
AB - Toll-like receptors (TLRs) act as the first line of defense against bacterial and
viral pathogens by initiating critical defense signals upon dimer activation. The
contribution of the transmembrane domain in the dimerization and signaling
process has heretofore been overlooked in favor of the extracellular and
intracellular domains. As mounting evidence suggests that the transmembrane
domain is a critical region in several protein families, we hypothesized that
this was also the case for Toll-like receptors. Using a combined biochemical and
biophysical approach, we investigated the ability of isolated Toll-like receptor
transmembrane domains to interact independently of extracellular domain
dimerization. Our results showed that the transmembrane domains had a preference
for the native dimer partners in bacterial membranes for the entire receptor
family. All TLR transmembrane domains showed strong homotypic interaction
potential. The TLR2 transmembrane domain demonstrated strong heterotypic
interactions in bacterial membranes with its known interaction partners, TLR1 and
TLR6, as well as with a proposed interaction partner, TLR10, but not with TLR4,
TLR5, or unrelated transmembrane receptors providing evidence for the specificity
of TLR2 transmembrane domain interactions. Peptides for the transmembrane domains
of TLR1, TLR2, and TLR6 were synthesized to further study this subfamily of
receptors. These peptides validated the heterotypic interactions seen in
bacterial membranes and demonstrated that the TLR2 transmembrane domain had
moderately strong interactions with both TLR1 and TLR6. Combined, these results
suggest a role for the transmembrane domain in Toll-like receptor oligomerization
and as such, may be a novel target for further investigation of new therapeutic
treatments of Toll-like receptor mediated diseases.
PMID- 23155422
TI - Prospective analysis of the association of a common variant of FTO (rs9939609)
with adiposity in children: results of the IDEFICS study.
AB - OBJECTIVES: We investigated cross-sectionally and longitudinally the relationship
between FTO rs9939609 and obesity-related characteristics in the European
children of the IDEFICS project and the interaction of this variant with a
lifestyle intervention. POPULATION AND METHODS: A cohort of 16224 children (2-9
years) was recruited into a population-based survey (T0) from eight European
countries. A second survey (T1) reassessed the children two years later. A random
sample of 4405 children was extracted for genetic studies. 3168 children were re
examined two years later. Half of them underwent a lifestyle intervention
program. The FTO rs9939609 was genotyped. Weight, height, waist circumference,
triceps and subscapular skinfolds were measured at T0 and T1. RESULTS: At T0, the
risk A allele of rs9939609 was significantly associated with higher values of
body mass index (BMI), waist circumference and skinfolds (age, sex, and country
adjusted p-values: all p<0.001) and with a statistically significant increased
risk of overweight/obesity. Over the two year follow-up, no interaction between
genotype and intervention was observed. The A allele was associated to a
significantly higher increase in all the anthropometric variables examined at T0
independently from the study group (intervention versus control) (p-values: all
p<0.002, adjusted for age, sex, country, intervention/control study group, T0
values, and individual time interval between T0 and T1). Over the two-year follow
up, 210 new cases of overweight/obesity occurred. A statistically significant
higher incidence of overweight/obesity was associated to the A allele [OR(A) =
1.95, 95% CI = (1.29; 2.97)]. CONCLUSIONS: We confirmed the association between
the FTO rs9939609 and body mass and overweight/obesity risk in European children.
The main finding of the study is that the A allele carriers present higher
increase of body mass and central adiposity over time and higher risk of
developing overweight/obesity during growth, independently from intervention
measures.
PMID- 23155423
TI - Impaired skeletal muscle regeneration in the absence of fibrosis during
hibernation in 13-lined ground squirrels.
AB - Skeletal muscle atrophy can occur as a consequence of immobilization and/or
starvation in the majority of vertebrates studied. In contrast, hibernating
mammals are protected against the loss of muscle mass despite long periods of
inactivity and lack of food intake. Resident muscle-specific stem cells
(satellite cells) are known to be activated by muscle injury and their activation
contributes to the regeneration of muscle, but whether satellite cells play a
role in hibernation is unknown. In the hibernating 13-lined ground squirrel we
show that muscles ablated of satellite cells were still protected against
atrophy, demonstrating that satellite cells are not involved in the maintenance
of skeletal muscle during hibernation. Additionally, hibernating skeletal muscle
showed extremely slow regeneration in response to injury, due to repression of
satellite cell activation and myoblast differentiation caused by a fine-tuned
interplay of p21, myostatin, MAPK, and Wnt signaling pathways. Interestingly,
despite long periods of inflammation and lack of efficient regeneration, injured
skeletal muscle from hibernating animals did not develop fibrosis and was capable
of complete recovery when animals emerged naturally from hibernation. We propose
that hibernating squirrels represent a new model system that permits evaluation
of impaired skeletal muscle remodeling in the absence of formation of tissue
fibrosis.
PMID- 23155424
TI - Adiponectin mediated MHC class II mismatched cardiac graft rejection in mice is
IL-4 dependent.
AB - BACKGROUND: Adiponectin regulates glucose and fatty-acid metabolism but its role
in chronic graft rejection mediated by Th2 cytokines remains ill-defined.
METHODOLOGY/PRINCIPAL FINDINGS: Wild type and adiponectin-null mice were used as
graft recipients in mouse MHC class II disparate cardiac transplantation (bm12
toB6) and the graft rejection was monitored. In adiponectin-null mice we observed
that the cellular infiltrate of eosinophils, CD4(+) and CD8(+) T cells was
reduced in grafts compared to the controls as was collagen deposition and vessel
occlusion. A similar outcome was observed for skin transplants except that
neutrophil infiltration was increased. Low levels of IL-4 were detected in the
grafts and serum. The effect of adiponectin signaling on IL-4 expression was
further investigated. Treatment with AMPK and p38 MAPK inhibitors blocked
adiponectin enhanced T cell proliferation in mixed lymphocyte reactions.
Inhibition of AMPK reduced eosinophil infiltration in skin grafts in wild type
recipients and in contrast AMPK activation increased eosinophils in adiponectin
null recipients. The addition of adiponectin increased IL-4 production by the T
cell line EL4 with augmented nuclear GATA-3 and phospho-STAT6 expression which
were suppressed by knockdown of adiponectin receptor 1 and 2. CONCLUSIONS: Our
results demonstrate a direct effect of adiponectin on IL-4 expression which
contributes to Th2 cytokine mediated rejection in mouse MHC class II
histoincompatible transplants. These results add to our understanding of the
interrelationship of metabolism and immune regulation and raise the possibility
that AMPK inhibitors may be beneficial in selected types of rejection.
PMID- 23155425
TI - Survival of Staphylococcus aureus ST398 in the human nose after artificial
inoculation.
AB - There is evidence that MRSA ST398 of animal origin is only capable of temporarily
occupying the human nose, and it is therefore, often considered a poor human
colonizer.We inoculated 16 healthy human volunteers with a mixture of the human
MSSA strain 1036 (ST931, CC8) and the bovine MSSA strain 5062 (ST398, CC398), 7
weeks after a treatment with mupirocin and chlorhexidine-containing soap.
Bacterial survival was studied by follow-up cultures over 21 days. The human
strain 1036 was eliminated faster (median 14 days; range 2-21 days) than the
bovine strain 5062 (median 21 days; range 7-21 days) but this difference was not
significant (p = 0.065). The bacterial loads were significantly higher for the
bovine strain on day 7 and day 21. 4/14 volunteers (28.6%) showed elimination of
both strains within 21 days. Of the 10 remaining volunteers, 5 showed no
differences in bacterial counts between both strains, and in the other 5 the
ST398 strain far outnumbered the human S. aureus strain. Within the 21 days of
follow-up, neither human strain 1036 nor bovine strain 5062 appeared to acquire
or lose any mobile genetic elements. In conclusion, S. aureus ST398 strain 5062
is capable of adequately competing for a niche with a human strain and survives
in the human nose for at least 21 days.
PMID- 23155426
TI - Isomeric mono-, di-, and tri-bromobenzo-1H-triazoles as inhibitors of human
protein kinase CK2alpha.
AB - To further clarify the role of the individual bromine atoms of 4,5,6,7
tetrabromotriazole (TBBt), a relatively selective inhibitor of protein kinase
CK2, we have examined the inhibition (IC(50)) of human CK2alpha by the two mono-,
the four di-, and the two tri- bromobenzotriazoles relative to that of TBBt.
Halogenation of the central vicinal C(5)/C(6) atoms proved to be a key factor in
enhancing inhibitory activity, in that 5,6-di-Br(2)Bt and 4,5,6-Br(3)Bt were
almost as effective inhibitors as TBBt, notwithstanding their marked differences
in pK(a) for dissociation of the triazole proton. The decrease in pK(a) on
halogenation of the peripheral C(4)/C(7) atoms virtually nullifies the gain due
to hydrophobic interactions, and does not lead to a decrease in IC(50). Molecular
modeling of structures of complexes of the ligands with the enzyme, as well as
QSAR analysis, pointed to a balance of hydrophobic and electrostatic interactions
as a discriminator of inhibitory activity. The role of halogen bonding remains
debatable, as originally noted for the crystal structure of TBBt with CK2alpha
(pdb1j91). Finally we direct attention to the promising applicability of our
series of well-defined halogenated benzotriazoles to studies on inhibition of
kinases other than CK2.
PMID- 23155427
TI - Visualizing sound emission of elephant vocalizations: evidence for two rumble
production types.
AB - Recent comparative data reveal that formant frequencies are cues to body size in
animals, due to a close relationship between formant frequency spacing, vocal
tract length and overall body size. Accordingly, intriguing morphological
adaptations to elongate the vocal tract in order to lower formants occur in
several species, with the size exaggeration hypothesis being proposed to justify
most of these observations. While the elephant trunk is strongly implicated to
account for the low formants of elephant rumbles, it is unknown whether elephants
emit these vocalizations exclusively through the trunk, or whether the mouth is
also involved in rumble production. In this study we used a sound visualization
method (an acoustic camera) to record rumbles of five captive African elephants
during spatial separation and subsequent bonding situations. Our results showed
that the female elephants in our analysis produced two distinct types of rumble
vocalizations based on vocal path differences: a nasally- and an orally-emitted
rumble. Interestingly, nasal rumbles predominated during contact calling, whereas
oral rumbles were mainly produced in bonding situations. In addition, nasal and
oral rumbles varied considerably in their acoustic structure. In particular, the
values of the first two formants reflected the estimated lengths of the vocal
paths, corresponding to a vocal tract length of around 2 meters for nasal, and
around 0.7 meters for oral rumbles. These results suggest that African elephants
may be switching vocal paths to actively vary vocal tract length (with
considerable variation in formants) according to context, and call for further
research investigating the function of formant modulation in elephant
vocalizations. Furthermore, by confirming the use of the elephant trunk in long
distance rumble production, our findings provide an explanation for the extremely
low formants in these calls, and may also indicate that formant lowering
functions to increase call propagation distances in this species'.
PMID- 23155428
TI - Angiotensin-converting enzyme 2 over-expression in the central nervous system
reduces angiotensin-II-mediated cardiac hypertrophy.
AB - Angiotensin-converting enzyme type 2 (ACE2) has been shown to be an important
member of the renin angiotensin system. Previously, we observed that central ACE2
reduces the development of hypertension following chronic angiotensin II (Ang-II)
infusion in syn-hACE2 transgenic (SA) mice, in which the human ACE2 transgene is
selectively targeted to neurons. To study the physiological consequences of
central ACE2 over-expression on cardiac function and cardiac hypertrophy, SA and
non-transgenic (NT) mice were infused with Ang-II (600 ng/kg/min, sc) for 14
days, and cardiac function was assessed by echocardiography. Blood pressure (BP),
hemodynamic parameters, left ventricle (LV) mass/tibia length, relative ventricle
wall thickness (2PW/LVD), cardiomyocyte diameters and collagen deposition were
similar (P>0.05) between NT and SA mice during saline infusion. After a 2-week
infusion, BP was elevated in NT but not in SA mice. Although ejection fraction
and fractional shortening were not altered, Ang-II infusion increased 2PW/LVD
compared to saline infusion in NT mice. Interestingly, the 2PW/LVD and LV
mass/tibia ratios were significantly lower in SA compared to NT mice at the end
of infusion. Moreover, Ang-II infusion significantly increased arterial collagen
deposition and cardiomyocytes diameter in NT mice but not in transgenic animals
(P<0.05). More importantly, ACE2 over expression significantly reduced the Ang-II
mediated increase in urine norepinephrine levels in SA compared to NT mice. The
protective effect of ACE2 appears to involve reductions in Ang-II-mediated
hypertension and sympathetic nerve activity.
PMID- 23155429
TI - Neurotensin and CRH interactions augment human mast cell activation.
AB - Stress affects immunity, but the mechanism is not known. Neurotensin (NT) and
corticotropin-releasing hormone (CRH) are secreted under stress in various
tissues, and have immunomodulatory actions. We had previously shown that NT
augments the ability of CRH to increase mast cell-dependent skin vascular
permeability in rodents. Here we show that NT triggered human mast cell
degranulation and significantly augmented CRH-induced vascular endothelial growth
factor (VEGF) release. Investigation of various signaling molecules indicated
that only NF-kappaB activation was involved. These effects were blocked by
pretreatment with the NTR antagonist SR48692. NT induced expression of CRH
receptor-1 (CRHR-1), as shown by Western blot and FACS analysis. Interestingly,
CRH also induced NTR gene and protein expression. These results indicate unique
interactions among NT, CRH, and mast cells that may contribute to auto-immune and
inflammatory diseases that worsen with stress.
PMID- 23155430
TI - Isolation and characterization of human dental pulp derived stem cells by using
media containing low human serum percentage as clinical grade substitutes for
bovine serum.
AB - Adult stem cells have been proposed as an alternative to embryonic stem cells to
study multilineage differentiation in vitro and to use in therapy. Current
culture media for isolation and expansion of adult stem cells require the use of
large amounts of animal sera, but animal-derived culture reagents give rise to
some questions due to the real possibility of infections and severe immune
reactions. For these reasons a clinical grade substitute to animal sera is
needed. We tested the isolation, proliferation, morphology, stemness related
marker expression, and osteoblastic differentiation potential of Dental Pulp Stem
Cells (DPSC) in a chemically defined medium containing a low percentage of human
serum, 1.25%, in comparison to a medium containing 10% Fetal Bovine Serum (FBS).
DPSCs cultured in presence of our isolation/proliferation medium added with low
HS percentage were obtained without immune-selection methods and showed high
uniformity in the expression of stem cell markers, proliferated at higher rate,
and demonstrated comparable osteoblastic potential with respect to DPSCs cultured
in 10% FBS. In this study we demonstrated that a chemically defined medium added
with low HS percentage, derived from autologous and heterologous sources, could
be a valid substitute to FBS-containing media and should be helpful for adult
stem cells clinical application.
PMID- 23155431
TI - Cardiac protection by preconditioning is generated via an iron-signal created by
proteasomal degradation of iron proteins.
AB - Ischemia associated injury of the myocardium is caused by oxidative damage during
reperfusion. Myocardial protection by ischemic preconditioning (IPC) was shown to
be mediated by a transient 'iron-signal' that leads to the accumulation of
apoferritin and sequestration of reactive iron released during the ischemia. Here
we identified the source of this 'iron signal' and evaluated its role in the
mechanisms of cardiac protection by hypoxic preconditioning. Rat hearts were
retrogradely perfused and the effect of proteasomal and lysosomal protease
inhibitors on ferritin levels were measured. The iron-signal was abolished,
ferritin levels were not increased and cardiac protection was diminished by
inhibition of the proteasome prior to IPC. Similarly, double amounts of ferritin
and better recovery after ex vivo ischemia-and-reperfusion (I/R) were found in
hearts from in vivo hypoxia pre-conditioned animals. IPC followed by normoxic
perfusion for 30 min ('delay') prior to I/R caused a reduced ferritin
accumulation at the end of the ischemia phase and reduced protection. Full
restoration of the IPC-mediated cardiac protection was achieved by employing
lysosomal inhibitors during the 'delay'. In conclusion, proteasomal protein
degradation of iron-proteins causes the generation of the 'iron-signal' by IPC,
ensuing de-novo apoferritin synthesis and thus, sequestering reactive iron.
Lysosomal proteases are involved in subsequent ferritin breakdown as revealed by
the use of specific pathway inhibitors during the 'delay'. We suggest that
proteasomal iron-protein degradation is a stress response causing an expeditious
cytosolic iron release thus, altering iron homeostasis to protect the myocardium
during I/R, while lysosomal ferritin degradation is part of housekeeping iron
homeostasis.
PMID- 23155432
TI - Early versus delayed insertion of intrauterine contraception after medical
abortion - a randomized controlled trial.
AB - BACKGROUND: Today, a large proportion of early abortions are medical
terminations, in accordance to the woman's choice. Intrauterine contraceptives
(IUC) provide highly effective, reversible, long-acting contraception. However,
the effects of timing of IUC insertion after medical abortion are not known.
METHODS: Women undergoing medical abortion with mifepristone and misoprostol up
to 63 days gestation and opting for IUC were randomised to early insertion (day 5
9 after mifepristone) or delayed (routine) insertion (at 3-4 weeks after
mifepristone). The primary outcome was the rate of IUC expulsion at six months
after IUC insertion. RESULTS: A total of 129 women were randomized, and 116 women
had a successful IUC insertion. There was no difference in expulsion rate between
early (9.7%) vs. delayed (7.4%) IUC insertion (risk difference -9.2-13.4).
Furthermore, 1.5% of women randomized to early and 11.5% to delayed insertion did
not attend the follow up (proportion difference 10.0%, 95% CI: 1.8-20.6%, p =
0.015), and a higher proportion of women (41%) had had unprotected intercourse
prior to returning for insertion in the delayed group compared with the early
group (16%) (p = 0.015). Adverse events were rare and did not differ between the
groups. CONCLUSIONS: Early insertion of IUC after medical abortion was safe and
well tolerated with no increased incidence for expulsions or complications. Women
were more likely to return for the IUC insertion if scheduled early after the
abortion, and less likely to have had an unprotected intercourse prior to the IUC
insertion. Early insertion should be offered as a routine for women undergoing
first trimester medical abortion. TRIAL REGISTRATION: ClinicalTrials.gov
NCT01537562.
PMID- 23155433
TI - Identification of nitrogen starvation-responsive microRNAs in Arabidopsis
thaliana.
AB - microRNAs (miRNAs) are a class of negative regulators that take part in many
processes such as growth and development, stress responses, and metabolism in
plants. Recently, miRNAs were shown to function in plant nutrient metabolism.
Moreover, several miRNAs were identified in the response to nitrogen (N)
deficiency. To investigate the functions of other miRNAs in N deficiency, deep
sequencing technology was used to detect the expression of small RNAs under N
sufficient and -deficient conditions. The results showed that members from the
same miRNA families displayed differential expression in response to N
deficiency. Upon N starvation, the expression of miR169, miR171, miR395, miR397,
miR398, miR399, miR408, miR827, and miR857 was repressed, whereas those of
miR160, miR780, miR826, miR842, and miR846 were induced. miR826, a newly
identified N-starvation-induced miRNA, was found to target the AOP2 gene. Among
these N-starvation-responsive miRNAs, several were involved in cross-talk among
responses to different nutrient (N, P, S, Cu) deficiencies. miR160, miR167, and
miR171 could be responsible for the development of Arabidopsis root systems under
N-starvation conditions. In addition, twenty novel miRNAs were identified and
nine of them were significantly responsive to N-starvation. This study represents
comprehensive expression profiling of N-starvation-responsive miRNAs and advances
our understanding of the regulation of N homeostasis mediated by miRNAs.
PMID- 23155434
TI - Cognitive biases toward Internet game-related pictures and executive deficits in
individuals with an Internet game addiction.
AB - BACKGROUND: The cue-related go/no-go switching task provides an experimental
approach to study individual's flexibility in changing situations. Because
Internet addiction disorder (IAD) belongs to the compulsive-impulsive spectrum of
disorders, it should present cognitive bias and executive functioning deficit
characteristics of some of these types of disorders. Until now, no studies have
been reported on cognitive bias and executive function involving mental
flexibility and response inhibition in IAD. METHODOLOGY/PRINCIPAL FINDINGS: A
total of 46 subjects who met the criteria of the modified Young's Diagnostic
Questionnaire for Internet addiction (YDQ) were recruited as an Internet game
addiction (IGA) group, along with 46 healthy control individuals. All
participants performed the Internet game-shifting task. Using hit rate, RT, d'
and C as the dependent measures, a three-way ANOVA (group * target * condition)
was performed. For hit rate, a significant effect of group, type of target and
condition were found. The group-target interaction effect was significant. For
RT, significant effects were revealed for group and type of target. The group
target interaction effect was significant. Comparisons of the means revealed that
the slowing down of IGA relative to NIA was more pronounced when the target
stimuli were neutral as opposed to Internet game-related pictures. In addition,
the group-condition interaction effect was significant. For d', significant
effects of group, type of target and condition were found. The group-target
interaction effect was significant. For C, the type of target produced a
significant effect. There was a positive correlation between the length of the
addiction (number of years) and the severity of the cognitive bias. CONCLUSIONS:
IGA present cognitive biases towards information related to Internet gaming.
These biases, as well as poor executive functioning skills (lower mental
flexibility and response inhibition), might be responsible for Internet game
addiction. The assessment of cognitive biases in IGA might provide a methodology
for evaluation of therapeutic effects.
PMID- 23155435
TI - Animal-borne acoustic transceivers reveal patterns of at-sea associations in an
upper-trophic level predator.
AB - Satellite telemetry data have substantially increased our understanding of
habitat use and foraging behaviour of upper-trophic marine predators, but fall
short of providing an understanding of their social behaviour. We sought to
determine whether novel acoustic and archival GPS data could be used to examine
at-sea associations among grey seals (Halichoerus grypus) during the fall
foraging period. Fifteen grey seals from Sable Island, Canada were deployed with
Vemco Mobile Transceivers and Satellite-GPS transmitters in October 2009, 13 of
which were recaptured and units retrieved 79 +/- 2.3 days later during the
following breeding season, December 2009-January 2010. An association between two
individuals was defined as a cluster of acoustic detections where the time
between detections was <30 min. Bathymetry, travel rate, and behavioural state
(slow and fast movement) were determined for each GPS archival point (3.7 +/- 0.1
locations recorded per hour). Behavioural state was estimated using a hidden
Markov model. All seals had been involved in associations with other instrumented
seals while at sea, with a total of 1,872 acoustic detections recorded in 201
associations. The median number of detections per association was 3 (range: 1
151) and the median duration of an association was 0.17 h (range: <0.1-11.3 h).
Linear mixed-effects models showed that associations occurred when seals were
exhibiting slow movement (0.24 +/- 0.01 ms(-1)) on shallow (53.4 +/- 3.7 m)
offshore banks where dominant prey is known to occur. These results suggest the
occurrence of short-term associations among multiple individuals at foraging
grounds and provide new insights into the foraging ecology of this upper-trophic
marine predator.
PMID- 23155436
TI - Cholesterol side-chain cleavage gene expression in theca cells: augmented
transcriptional regulation and mRNA stability in polycystic ovary syndrome.
AB - Hyperandrogenism is characteristic of women with polycystic ovary syndrome
(PCOS). Ovarian theca cells isolated from PCOS follicles and maintained in long
term culture produce elevated levels of progestins and androgens compared to
normal theca cells. Augmented steroid production in PCOS theca cells is
associated with changes in the expression of genes for several steroidogenic
enzymes, including CYP11A1, which encodes cytochrome P450 cholesterol side-chain
cleavage. Here, we further examined CYP11A1 gene expression, at both the
transcriptional and post-transcriptional level in normal and PCOS theca cells
propagated in long-term culture utilizing quantitative RT-PCR, functional
promoter analyses, and mRNA degradation studies. The minimal element(s) that
conferred increased basal and cAMP-dependent CYP11A1 promoter function were
determined. CYP11A1 mRNA half-life in normal and PCOS theca cells was compared.
Results of these cumulative studies showed that basal and forskolin stimulated
steady state CYP11A1 mRNA abundance and CYP11A1 promoter activity were increased
in PCOS theca cells. Deletion analysis of the CYP11A1 promoter demonstrated that
augmented promoter function in PCOS theca cells results from increased basal
regulation conferred by a minimal sequence between -160 and -90 bp of the
transcriptional start site. The transcription factor, nuclear factor 1C2, was
observed to regulate basal activity of this minimal CYP11A1 element. Examination
of mRNA stability in normal and PCOS theca cells demonstrated that CYP11A1 mRNA
half-life increased >2-fold, from approximately 9.22+/-1.62 h in normal cells, to
22.38+/-0.92 h in PCOS cells. Forskolin treatment did not prolong CYP11A1 mRNA
stability in either normal or PCOS theca cells. The 5'-UTR of CYP11A1 mRNA
confers increased basal mRNA stability in PCOS cells. In conclusion, these
studies show that elevated steady state CYP11A1 mRNA abundance in PCOS cells
results from increased transactivation of the CYP11A1 promoter and increased
CYP11A1 mRNA stability.
PMID- 23155437
TI - Inflamm-aging and arachadonic acid metabolite differences with stage of tendon
disease.
AB - The contribution of inflammation to the pathogenesis of tendinopathy and high
prevalence of re-injury is not well established, although recent evidence
suggests involvement of prostaglandins. We investigated the roles of
prostaglandins and inflammation-resolving mediators in naturally occurring equine
tendon injury with disease stage and age. Levels of prostaglandins E(2) (PGE(2)),
F(2alpha) (PGF(2alpha)), lipoxin A(4) (LXA(4)) and its receptor FPR2/ALX were
analysed in extracts of normal, sub-acute and chronic injured tendons. To assess
whether potential changes were associated with altered PGE(2) metabolism,
microsomal prostaglandin E synthase-1 (mPGES-1), prostaglandin dehydrogenase
(PGDH), COX-2 and EP(4) receptor expression were investigated. The ability of
tendons to resolve inflammation was determined by assessing FPR2/ALX expression
in natural injury and IL-1beta stimulated tendon explants.Alterations in the
profile of lipid mediators during sub-acute injury included low PGE(2) and
elevated LXA(4) levels compared to normal and chronic injuries. In contrast,
PGF(2alpha) levels remained unchanged and were three-fold lower than PGE(2). The
synthetic capacity of PGE(2) as measured by the ratio of mPGES-1:PGDH was
elevated in sub-acute injury, suggesting aberrations in tendon prostaglandin
metabolism, whilst COX-2 and EP(4) receptor were unchanged. Paradoxically low
tendon PGE(2) levels in early injury may be attributed to increased local
clearance via PGDH or the class switching of lipid mediators from the
prostaglandin to the lipoxin axis. PGE(2) is therefore implicated in the
development of tendon inflammation and its ensuing resolution. Whilst there was
no relationship between age and tendon LXA(4) levels, there was an age-associated
decline in FPR2/ALX receptor expression with concurrent increased PGE(2) levels
in injury. Furthermore, uninjured tendon explants from younger (<10 years) but
not older horses (>=10 years) treated with IL-1beta responded by increasing
FPR2/ALX suggesting aged individuals exhibit a reduced capacity to resolve
inflammation via FPR2/ALX, which may present a potential mechanism for
development of chronic tendinopathy and re-injury.
PMID- 23155439
TI - Kretzoiarctos gen. nov., the oldest member of the giant panda clade.
AB - The phylogenetic position of the giant panda, Ailuropoda melanoleuca (Carnivora:
Ursidae: Ailuropodinae), has been one of the most hotly debated topics by
mammalian biologists and paleontologists during the last century. Based on
molecular data, it is currently recognized as a true ursid, sister-taxon of the
remaining extant bears, from which it would have diverged by the Early Miocene.
However, from a paleobiogeographic and chronological perspective, the origin of
the giant panda lineage has remained elusive due to the scarcity of the available
Miocene fossil record. Until recently, the genus Ailurarctos from the Late
Miocene of China (ca. 8-7 mya) was recognized as the oldest undoubted member of
the Ailuropodinae, suggesting that the panda lineage might have originated from
an Ursavus ancestor. The role of the purported ailuropodine Agriarctos, from the
Miocene of Europe, in the origins of this clade has been generally dismissed due
to the paucity of the available material. Here, we describe a new ailuropodine
genus, Kretzoiarctos gen. nov., based on remains from two Middle Miocene (ca. 12
11 Ma) Spanish localities. A cladistic analysis of fossil and extant members of
the Ursoidea confirms the inclusion of the new genus into the Ailuropodinae.
Moreover, Kretzoiarctos precedes in time the previously-known, Late Miocene
members of the giant panda clade from Eurasia (Agriarctos and Ailurarctos). The
former can be therefore considered the oldest recorded member of the giant panda
lineage, which has significant implications for understanding the origins of this
clade from a paleobiogeographic viewpoint.
PMID- 23155438
TI - Genetic overlap between apparently sporadic motor neuron diseases.
AB - Progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS) are
devastating motor neuron diseases (MNDs), which result in muscle weakness and/or
spasticity. We compared mutation frequencies in genes known to be associated with
MNDs between patients with apparently sporadic PMA and ALS. A total of 261
patients with adult-onset sporadic PMA, patients with sporadic ALS, and control
subjects of Dutch descent were obtained at national referral centers for
neuromuscular diseases in The Netherlands. Sanger sequencing was used to screen
these subjects for mutations in the coding regions of superoxide dismutase-1
(SOD1), angiogenin (ANG), fused in sarcoma/translated in liposarcoma (FUS/TLS),
TAR DNA-binding protein 43 (TARDBP), and multivesicular body protein 2B (CHMP2B).
In our cohort of PMA patients we identified two SOD1 mutations (p.D90A, p.I113T),
one ANG mutation (p.K17I), one FUS/TLS mutation (p.R521H), one TARDBP mutation
(p.N352S), and one novel CHMP2B mutation (p.R69Q). The mutation frequency of
these genes was similar in sporadic PMA (2.7%) and ALS (2.0%) patients, and
therefore, our findings demonstrate a genetic overlap between apparently sporadic
PMA and ALS.
PMID- 23155440
TI - A novel two-component system involved in secretion stress response in
Streptomyces lividans.
AB - BACKGROUND: Misfolded proteins accumulating outside the bacterial cytoplasmic
membrane can interfere with the secretory machinery, hence the existence of
quality factors to eliminate these misfolded proteins is of capital importance in
bacteria that are efficient producers of secretory proteins. These bacteria
normally use a specific two-component system to respond to the stress produced by
the accumulation of the misfolded proteins, by activating the expression of HtrA
like proteases to specifically eliminate the incorrectly folded proteins.
METHODOLOGY/PRINCIPAL FINDINGS: Overproduction of alpha-amylase in S. lividans
causing secretion stress permitted the identification of a two-component system
(SCO4156-SCO4155) that regulates three HtrA-like proteases which appear to be
involved in secretion stress response. Mutants in each of the genes forming part
of the two-genes operon that encodes the sensor and regulator protein components
accumulated misfolded proteins outside the cell, strongly suggesting the
involvement of this two-component system in the S. lividans secretion stress
response. CONCLUSIONS/SIGNIFICANCE: To our knowledge this is the first time that
a specific secretion stress response two-component system is found to control the
expression of three HtrA-like protease genes in S. lividans, a bacterium that has
been repeatedly used as a host for the synthesis of homologous and heterologous
secretory proteins of industrial application.
PMID- 23155441
TI - Cancer risk of anti-TNF-alpha at recommended doses in adult rheumatoid arthritis:
a meta-analysis with intention to treat and per protocol analyses.
AB - BACKGROUND: The risk of malignancies on TNF-alpha antagonists is controversial.
The aim of this survey was to assess cancer risk on TNF-alpha antagonists in
adult rheumatoid arthritis patients, including the five marketed drugs
(infliximab, etanercept, adalimumab, golimumab and certolizumab) used in line
with the New Drug Application. Furthermore, the relative interest of modified
intention to treat or per protocol analyses to assess such sparse events remains
unknown. METHODOLOGY/PRINCIPAL FINDINGS: Data sources were MEDLINE, CENTRAL, ISI
Web of Science, ACR and EULAR meeting abstracts, scientific evaluation of the
drugs leading to their marketing approval, and clinicaltrials.gov, until 31
December 2012.We selected double-blind randomized controlled trials in adult
rheumatoid arthritis patients, including at least one treatment arm in line with
New Drug Application. We performed random effect meta-analysis, with modified
intention to treat and per protocol analyses. Thirty-three trials were included.
There was no excess risk of malignancies on anti-TNF-alpha administered in line
with New Drug Application in the per protocol model (OR, 0.93 95%CI[0.59-1.44]),
as well as in the modified intention to treat model (OR, 1.27 95%CI[0.82-1.98]).
There was a non-significant tendency for an excess non-melanoma skin cancer risk
in both models (respectively, 1.37 [0.71-2.66] and 1.90 [0.98-3.67]). With fixed
effect Peto model restricting to trials during at least 52 weeks, the overall
cancer risk was respectively 1.60 [0.97-2.64] and 1.22 [0.72-2.08]. Whatever the
model, modified intention to treat analysis led to higher estimations than per
protocol analysis. The later may underestimate the treatment effect when
assessing very sparse events and when many patients dropped out in placebo arms.
In metaregression, there was no differential risk among the five drugs.
CONCLUSIONS/SIGNIFICANCE: This study did not find any evidence for an excess
cancer risk on TNF-alpha antagonists in adult rheumatoid arthritis patients, but
an excess cancer risk after several years of exposure cannot be ruled out. Both
modified intention to treat and per protocol analyses should be presented in such
safety analyses.
PMID- 23155442
TI - Cross-species functional genomic analysis identifies resistance genes of the
histone deacetylase inhibitor valproic acid.
AB - The mechanisms of successful epigenetic reprogramming in cancer are not well
characterized as they involve coordinated removal of repressive marks and
deposition of activating marks by a large number of histone and DNA modification
enzymes. Here, we have used a cross-species functional genomic approach to
identify conserved genetic interactions to improve therapeutic effect of the
histone deacetylase inhibitor (HDACi) valproic acid, which increases survival in
more than 20% of patients with advanced acute myeloid leukemia (AML). Using a
bidirectional synthetic lethality screen revealing genes that increased or
decreased VPA sensitivity in C. elegans, we identified novel conserved
sensitizers and synthetic lethal interactors of VPA. One sensitizer identified as
a conserved determinant of therapeutic success of HDACi was UTX (KDM6A), which
demonstrates a functional relationship between protein acetylation and lysine
specific methylation. The synthetic lethal screen identified resistance programs
that compensated for the HDACi-induced global hyper-acetylation, and confirmed
MAPKAPK2, HSP90AA1, HSP90AB1 and ACTB as conserved hubs in a resistance program
for HDACi that are drugable in human AML cell lines. Hence, these resistance hubs
represent promising novel targets for refinement of combinatorial epigenetic anti
cancer therapy.
PMID- 23155443
TI - Dynamics of intraocular IFN-gamma, IL-17 and IL-10-producing cell populations
during relapsing and monophasic rat experimental autoimmune uveitis.
AB - A major limitation of most animal models of autoimmune diseases is that they do
not reproduce the chronic or relapsing-remitting pattern characteristic of many
human autoimmune diseases. This problem has been overcome in our rat models of
experimentally induced monophasic or relapsing-remitting autoimmune uveitis
(EAU), which depend on the inducing antigen peptides from retinal S-Antigen
(monophasic EAU) or interphotoreceptor retinoid-binding protein (relapsing EAU).
These models enable us to compare autoreactive and regulatory T cell populations.
Intraocular, but not peripheral T cells differ in their cytokine profiles (IFN
gamma, IL-17 and IL-10) at distinct time points during monophasic or relapsing
EAU. Only intraocular T cells concomitantly produced IFN-gamma, IL-17 and/or IL
10. Monophasic EAU presented rising numbers of cells expressing IFN-gamma and IL
17 (Th1/Th17) and cells expressing IL-10 or Foxp3. During relapsing uveitis an
increase of intraocular IFN-gamma+ cells and a concomitant decrease of IL-17+
cells was detected, while IL-10+ populations remained stable. Foxp3+ cells and
cells expressing IL-10, even in combination with IFN-gamma or IL-17, increased
during the resolution of monophasic EAU, suggesting a regulatory role for these T
cells. In general, cells producing multiple cytokines increased in monophasic and
decreased in relapsing EAU. The distinct appearance of certain intraocular
populations with characteristics of regulatory cells points to a differential
influence of the ocular environment on T cells that induce acute and monophasic
or relapsing disease. Here we provide evidence that different autoantigens can
elicit distinct and differently regulated immune responses. IFN-gamma, but not IL
17 seems to be the key player in relapsing-remitting uveitis, as shown by
increased, synchronized relapses after intraocular application of IFN-gamma. We
demonstrated dynamic changes of the cytokine pattern during monophasic and
relapsing-remitting disease with strongly increasing IL-10 expression in
intraocular T cells during monophasic uveitis.
PMID- 23155444
TI - Please don't! The automatic extrapolation of dangerous intentions.
AB - Facial emotions and emotional body postures can easily grab attention in social
communication. In the context of faces, gaze has been shown as an important cue
for orienting attention, but less is known for other important body parts such as
hands. In the present study we investigated whether hands may orient attention
due to the emotional features they convey. By implying motion in static
photographs of hands, we aimed at furnishing observers with information about the
intention to act and at testing if this interacted with the hand automatic
coding. In this study, we compared neutral and frontal hands to emotionally
threatening hands, rotated along their radial-ulnar axes in a Sidedness task (a
Simon-like task based on automatic access to body representation). Results showed
a Sidedness effect for both the palm and the back views with either neutral and
emotional hands. More important, no difference was found between the two views
for neutral hands, but it emerged in the case of the emotional hands: faster
reaction times were found for the palm than the back view. The difference was
ascribed to palm views' "offensive" pose: a source of threat that might have
raised participants' arousal. This hypothesis was also supported by conscious
evaluations of the dimensions of valence (pleasant-unpleasant) and arousal.
Results are discussed in light of emotional feature coding.
PMID- 23155445
TI - Purkinje cell maturation participates in the control of oligodendrocyte
differentiation: role of sonic hedgehog and vitronectin.
AB - Oligodendrocyte differentiation is temporally regulated during development by
multiple factors. Here, we investigated whether the timing of oligodendrocyte
differentiation might be controlled by neuronal differentiation in cerebellar
organotypic cultures. In these cultures, the slices taken from newborn mice show
very few oligodendrocytes during the first week of culture (immature slices)
whereas their number increases importantly during the second week (mature
slices). First, we showed that mature cerebellar slices or their conditioned
media stimulated oligodendrocyte differentiation in immature slices thus
demonstrating the existence of diffusible factors controlling oligodendrocyte
differentiation. Using conditioned media from different models of slice culture
in which the number of Purkinje cells varies drastically, we showed that the
effects of these differentiating factors were proportional to the number of
Purkinje cells. To identify these diffusible factors, we first performed a
transcriptome analysis with an Affymetrix array for cerebellar cortex and then
real-time quantitative PCR on mRNAs extracted from fluorescent flow cytometry
sorted (FACS) Purkinje cells of L7-GFP transgenic mice at different ages. These
analyses revealed that during postnatal maturation, Purkinje cells down-regulate
Sonic Hedgehog and up-regulate vitronectin. Then, we showed that Sonic Hedgehog
stimulates the proliferation of oligodendrocyte precursor cells and inhibits
their differentiation. In contrast, vitronectin stimulates oligodendrocyte
differentiation, whereas its inhibition with blocking antibodies abolishes the
conditioned media effects. Altogether, these results suggest that Purkinje cells
participate in controlling the timing of oligodendrocyte differentiation in the
cerebellum through the developmentally regulated expression of diffusible
molecules such as Sonic Hedgehog and vitronectin.
PMID- 23155447
TI - Barley HvHMA1 is a heavy metal pump involved in mobilizing organellar Zn and Cu
and plays a role in metal loading into grains.
AB - Heavy metal transporters belonging to the P(1B)-ATPase subfamily of P-type
ATPases are key players in cellular heavy metal homeostasis. Heavy metal
transporters belonging to the P(1B)-ATPase subfamily of P-type ATPases are key
players in cellular heavy metal homeostasis. In this study we investigated the
properties of HvHMA1, which is a barley orthologue of Arabidopsis thaliana AtHMA1
localized to the chloroplast envelope. HvHMA1 was localized to the periphery of
chloroplast of leaves and in intracellular compartments of grain aleurone cells.
HvHMA1 expression was significantly higher in grains compared to leaves. In
leaves, HvHMA1 expression was moderately induced by Zn deficiency, but reduced by
toxic levels of Zn, Cu and Cd. Isolated barley chloroplasts exported Zn and Cu
when supplied with Mg-ATP and this transport was inhibited by the AtHMA1
inhibitor thapsigargin. Down-regulation of HvHMA1 by RNA interference did not
have an effect on foliar Zn and Cu contents but resulted in a significant
increase in grain Zn and Cu content. Heterologous expression of HvHMA1 in heavy
metal-sensitive yeast strains increased their sensitivity to Zn, but also to Cu,
Co, Cd, Ca, Mn, and Fe. Based on these results, we suggest that HvHMA1 is a broad
specificity exporter of metals from chloroplasts and serve as a scavenging
mechanism for mobilizing plastid Zn and Cu when cells become deficient in these
elements. In grains, HvHMA1 might be involved in mobilizing Zn and Cu from the
aleurone cells during grain filling and germination.
PMID- 23155446
TI - Interaction of inflammation and hyperoxia in a rat model of neonatal white matter
damage.
AB - Intrauterine infection and inflammation are major reasons for preterm birth. The
switch from placenta-mediated to lung-mediated oxygen supply during birth is
associated with a sudden rise of tissue oxygen tension that amounts to relative
hyperoxia in preterm infants. Both infection/inflammation and hyperoxia have been
shown to be involved in brain injury of preterm infants. Hypothesizing that they
might be additive or synergistic, we investigated the influence of a systemic
lipopolysaccharide (LPS) application on hyperoxia-induced white matter damage
(WMD) in newborn rats. Three-day-old Wistar rat pups received 0.25 mg/kg LPS i.p.
and were subjected to 80% oxygen on P6 for 24 h. The extent of WMD was assessed
by immunohistochemistry, western blots, and diffusion tensor (DT) magnetic
resonance imaging (MRI). In addition, the effects of LPS and hyperoxia were
studied in an in vitro co-culture system of primary rat oligodendrocytes and
microglia cells. Both noxious stimuli, hyperoxia, and LPS caused hypomyelination
as revealed by western blot, immunohistochemistry, and altered WM microstructure
on DT-MRI. Even so, cellular changes resulting in hypomyelination seem to be
different. While hyperoxia induces cell death, LPS induces oligodendrocyte
maturity arrest without cell death as revealed by TUNEL-staining and
immunohistological maturation analysis. In the two-hit scenario cell death is
reduced compared with hyperoxia treated animals, nevertheless white matter
alterations persist. Concordantly with these in vivo findings we demonstrate that
LPS pre-incubation reduced premyelinating-oligodendrocyte susceptibility towards
hyperoxia in vitro. This protective effect might be caused by upregulation of
interleukin-10 and superoxide dismutase expression after LPS stimulation. Reduced
expression of transcription factors controlling oligodendrocyte development and
maturation further indicates oligodendrocyte maturity arrest. The knowledge about
mechanisms that triggered hypomyelination contributes to a better understanding
of WMD in premature born infants.
PMID- 23155448
TI - The association between four genetic variants in microRNAs (rs11614913,
rs2910164, rs3746444, rs2292832) and cancer risk: evidence from published
studies.
AB - MicroRNAs (miRNAs) participate in diverse biological pathways and may act as
either tumor suppressor genes or oncogenes. Single nucleotide polymorphisms
(SNPs) in miRNA may contribute to cancer development with changes in the
microRNA's properties and/or maturation. Polymorphisms in miRNAs have been
suggested in predisposition to cancer risk; however, accumulated studies have
shown inconsistent conslusionss. To further validate determine whether there is
any potential association between the four common SNPs (miR-196a2C>T, rs11614913;
miR-146aG>C, rs2910164; miR-499A>G, rs3746444; miR-149C>T, rs2292832) and the
risk for developing risk, a meta-analysis was performed according to the 40
published case-control studies. Odds ratios (ORs) with 95% confidence intervals
(CIs) were calculated to assess the extent of the association. The results
demonstrated that the rs11614913TT genotype was significantly associated with a
decreased cancer risk, in particular with a decreased risk for colorectal cancer
and lung cancer, or for Asian population subgroup. In addition, the rs2910164C
allele was associated with decreased risk for esophageal cancer, cervical cancer,
prostate cancer, and hepatocellular carcinoma (HCC), in particular in Asian
population subgroup. Similarly, the rs3746444G allele was observed as a risk
factor for cancers in the Asian population. It is concluded that two SNPs prsent
in miRNAs(rs11614913TT, and rs2910164C) may protect against the pathogenesis of
some cancers, and that the rs3746444 may increase risk for cancer.
PMID- 23155449
TI - Probing mixed-genotype infections I: extraction and cloning of infections from
hosts of the trypanosomatid Crithidia bombi.
AB - We here present an efficient, precise and reliable method to isolate and
cultivate healthy and viable single Crithidia bombi cells from bumblebee faeces
using flow cytometry. We report a precision of >99% in obtaining single
trypanosomatid cells for further culture and analysis ("cloning"). In the study,
we have investigated the use of different liquid media to cultivate C. bombi and
present an optimal medium for obtaining viable clones from all tested, infected
host donors. We show that this method can be applied to genotype a collection of
clones from natural infections. Furthermore, we show how to cryo-preserve C.
bombi cells to be revived to become infective clones after at least 4 years of
storage. Considering the high prevalence of infections in natural populations,
our method provides a powerful tool in studying the level and diversity of these
infections, and thus enriches the current methodology for the studies of complex
host-parasite interactions.
PMID- 23155450
TI - Effect of intentional bias on agency attribution of animated motion: an event
related fMRI study.
AB - Animated movements of simple geometric shapes can readily be interpreted as
depicting social events in which animate agents are engaged in intentional
activity. However, the brain regions associated with such intention have not been
clearly elucidated. In this study, intentional bias was manipulated using shape
and pattern animations while measuring associated brain activity using event
related functional magnetic resonance imaging (fMRI). Twenty-five higher
intention involved and twenty-five lower-intention involved animations were
presented to participants. Behavioral results showed that the degree of agency
attribution of the mental state increased as intentional involvement increased.
fMRI results revealed that the posterior superior temporal sulcus (STS), inferior
temporal gyrus (ITG), inferior frontal gyrus (IFG), premotor, temporal pole,
supramarginal gyrus, and superior parietal lobule (SPL) were activated while
participants viewed the high-intention animations. In contrast, occipital,
lingual, and middle frontal gyri were activated while the participants viewed the
low-intention animations. These findings suggest that as agent attribution
increases, the visual brain changes its functional role to the intentional brain
and becomes a flexible network for processing information about social
interaction.
PMID- 23155451
TI - Genetic footprints of Iberian cattle in America 500 years after the arrival of
Columbus.
AB - BACKGROUND: American Creole cattle presumably descend from animals imported from
the Iberian Peninsula during the period of colonization and settlement, through
different migration routes, and may have also suffered the influence of cattle
directly imported from Africa. The introduction of European cattle, which began
in the 18th century, and later of Zebu from India, has threatened the survival of
Creole populations, some of which have nearly disappeared or were admixed with
exotic breeds. Assessment of the genetic status of Creole cattle is essential for
the establishment of conservation programs of these historical resources.
METHODOLOGY/PRINCIPAL FINDINGS: We sampled 27 Creole populations, 39 Iberian, 9
European and 6 Zebu breeds. We used microsatellite markers to assess the origins
of Creole cattle, and to investigate the influence of different breeds on their
genetic make-up. The major ancestral contributions are from breeds of southern
Spain and Portugal, in agreement with the historical ports of departure of ships
sailing towards the Western Hemisphere. This Iberian contribution to Creoles may
also include some African influence, given the influential role that African
cattle have had in the development of Iberian breeds, but the possibility of a
direct influence on Creoles of African cattle imported to America can not be
discarded. In addition to the Iberian influence, the admixture with other
European breeds was minor. The Creoles from tropical areas, especially those from
the Caribbean, show clear signs of admixture with Zebu. CONCLUSIONS/SIGNIFICANCE:
Nearly five centuries since cattle were first brought to the Americas, Creoles
still show a strong and predominant signature of their Iberian ancestors. Creole
breeds differ widely from each other, both in genetic structure and influences
from other breeds. Efforts are needed to avoid their extinction or further
genetic erosion, which would compromise centuries of selective adaptation to a
wide range of environmental conditions.
PMID- 23155452
TI - Physiological responses in relation to performance during competition in elite
synchronized swimmers.
AB - PURPOSE: We aimed to characterize the cardiovascular, lactate and perceived
exertion responses in relation to performance during competition in junior and
senior elite synchronized swimmers. METHODS: 34 high level senior (21.4 +/- 3.6
years) and junior (15.9 +/- 1.0) synchronized swimmers were monitored while
performing a total of 96 routines during an official national championship in the
technical and free solo, duet and team competitive programs. Heart rate was
continuously monitored. Peak blood lactate was obtained from serial capillary
samples during recovery. Post-exercise rate of perceived exertion was assessed
using the Borg CR-10 scale. Total competition scores were obtained from official
records. RESULTS: Data collection was complete in 54 cases. Pre-exercise mean
heart rate (beats.min(-1)) was 129.1 +/- 13.1, and quickly increased during the
exercise to attain mean peak values of 191.7 +/- 8.7, with interspersed
bradycardic events down to 88.8 +/- 28.5. Mean peak blood lactate (mmol.L(-1))
was highest in the free solo (8.5 +/- 1.8) and free duet (7.6 +/- 1.8) and lowest
at the free team (6.2 +/- 1.9). Mean RPE (0-10+) was higher in juniors (7.8 +/-
0.9) than in seniors (7.1 +/- 1.4). Multivariate analysis revealed that heart
rate before and minimum heart rate during the routine predicted 26% of
variability in final total score. CONCLUSIONS: Cardiovascular responses during
competition are characterized by intense anticipatory pre-activation and rapidly
developing tachycardia up to maximal levels with interspersed periods of marked
bradycardia during the exercise bouts performed in apnea. Moderate blood lactate
accumulation suggests an adaptive metabolic response as a result of the specific
training adaptations attributed to influence of the diving response in
synchronized swimmers. Competitive routines are perceived as very to extremely
intense, particularly in the free solo and duets. The magnitude of anticipatory
heart rate activation and bradycardic response appear to be related to
performance variability.
PMID- 23155453
TI - Reduced neonatal mortality in Meishan piglets: a role for hepatic fatty acids?
AB - The Meishan pig breed exhibits increased prolificacy and reduced neonatal
mortality compared to commercial breeds, such as the Large White, prompting
breeders to introduce the Meishan genotype into commercial herds. Commercial
piglets are highly susceptible to hypoglycemia, hypothermia, and death,
potentially due to limited lipid stores and/or delayed hepatic metabolic ability.
We therefore hypothesized that variation in hepatic development and lipid
metabolism could contribute to the differences in neonatal mortality between
breeds. Liver samples were obtained from piglets of each breed on days 0, 7, and
21 of postnatal age and subjected to molecular and biochemical analysis. At
birth, both breeds exhibited similar hepatic glycogen contents, despite Meishan
piglets having significantly lower body weight. The livers from newborn Meishan
piglets exhibited increased C18?1n9C and C20?1n9 but lower C18?0, C20?4n6, and
C22?6n3 fatty acid content. Furthermore, by using an unsupervised machine
learning approach, we detected an interaction between C18?1n9C and glycogen
content in newborn Meishan piglets. Bioinformatic analysis could identify unique
age-based clusters from the lipid profiles in Meishan piglets that were not
apparent in the commercial offspring. Examination of the fatty acid signature
during the neonatal period provides novel insights into the body composition of
Meishan piglets that may facilitate liver responses that prevent hypoglycaemia
and reduce offspring mortality.
PMID- 23155454
TI - ERMO3/MVP1/GOLD36 is involved in a cell type-specific mechanism for maintaining
ER morphology in Arabidopsis thaliana.
AB - The endoplasmic reticulum (ER) has a unique, network-like morphology. The ER
structures are composed of tubules, cisternae, and three-way junctions. This
morphology is highly conserved among eukaryotes, but the molecular mechanism that
maintains ER morphology has not yet been elucidated. In addition, certain
Brassicaceae plants develop a unique ER-derived organelle called the ER body.
This organelle accumulates large amounts of PYK10, a beta-glucosidase, but its
physiological functions are still obscure. We aimed to identify a novel factor
required for maintaining the morphology of the ER, including ER bodies, and
employed a forward-genetic approach using transgenic Arabidopsis thaliana (GFP-h)
with fluorescently-labeled ER. We isolated and investigated a mutant (designated
endoplasmic reticulum morphology3, ermo3) with huge aggregates and abnormal
punctate structures of ER. ERMO3 encodes a GDSL-lipase/esterase family protein,
also known as MVP1. Here, we showed that, although ERMO3/MVP1/GOLD36 was
expressed ubiquitously, the morphological defects of ermo3 were specifically seen
in a certain type of cells where ER bodies developed. Coimmunoprecipitation
analysis combined with mass spectrometry revealed that ERMO3/MVP1/GOLD36
interacts with the PYK10 complex, a huge protein complex that is thought to be
important for ER body-related defense systems. We also found that the depletion
of transcription factor NAI1, a master regulator for ER body formation,
suppressed the formation of ER-aggregates in ermo3 cells, suggesting that NAI1
expression plays an important role in the abnormal aggregation of ER. Our results
suggest that ERMO3/MVP1/GOLD36 is required for preventing ER and other organelles
from abnormal aggregation and for maintaining proper ER morphology in a
coordinated manner with NAI1.
PMID- 23155455
TI - Genome-wide expression analysis in Down syndrome: insight into immunodeficiency.
AB - Down syndrome (DS) is caused by triplication of Human chromosome 21 (Hsa21) and
associated with an array of deleterious phenotypes, including mental retardation,
heart defects and immunodeficiency. Genome-wide expression patterns of uncultured
peripheral blood cells are useful to understanding of DS-associated immune
dysfunction. We used a Human Exon microarray to characterize gene expression in
uncultured peripheral blood cells derived from DS individuals and age-matched
controls from two age groups: neonate (N) and child (C). A total of 174
transcript clusters (gene-level) with eight located on Hsa21 in N group and 383
transcript clusters including 56 on Hsa21 in C group were significantly
dysregulated in DS individuals. Microarray data were validated by quantitative
polymerase chain reaction. Functional analysis revealed that the dysregulated
genes in DS were significantly enriched in two and six KEGG pathways in N and C
group, respectively. These pathways included leukocyte trans-endothelial
migration, B cell receptor signaling pathway and primary immunodeficiency, etc.,
which causally implicated dysfunctional immunity in DS. Our results provided a
comprehensive picture of gene expression patterns in DS at the two developmental
stages and pointed towards candidate genes and molecular pathways potentially
associated with the immune dysfunction in DS.
PMID- 23155456
TI - FTO at rs9939609, food responsiveness, emotional control and symptoms of ADHD in
preschool children.
AB - The FTO minor allele at rs9939609 has been associated with body mass index (BMI:
weight (kg)/height (m)(2)) in children from 5 years onwards, food intake, and
eating behaviour. The high expression of FTO in the brain suggests that this gene
may also be associated with behavioural phenotypes, such as impulsivity and
control. We examined the effect of the FTO minor allele (A) at rs9939609 on
eating behaviour, impulsivity and control in young children, thus before the BMI
effect becomes apparent. This study was embedded in the Generation R Study, a
population-based cohort from fetal life onwards. 1,718 children of European
descent were genotyped for FTO at rs9939609. With logistic regression assuming an
additive genetic model, we examined the association between the FTO minor allele
and eating behaviour, impulsivity and control in preschool children. There was no
relation between FTO at rs9939609 and child BMI at this age. The A allele at
rs9939609 was associated with increased food responsiveness (OR 1.21, p = 0.03).
Also, children with the A allele were less likely to have symptoms of ADHD (OR
0.74, p = 0.01) and showed more emotional control (OR 0.64, p = 0.01) compared to
children without the A allele. Our findings suggest that before the association
between FTO and BMI becomes apparent, the FTO minor allele at rs9939609 leads to
increased food responsiveness, a decreased risk for symptoms of ADHD and better
emotional control. Future studies are needed to investigate whether these
findings represent one single mechanism or reflect pleiotropic effects of FTO.
PMID- 23155457
TI - High-throughput microRNA (miRNAs) arrays unravel the prognostic role of MiR-211
in pancreatic cancer.
AB - BACKGROUND: Only a subset of radically resected pancreatic ductal adenocarcinoma
(PDAC) patients benefit from chemotherapy, and identification of prognostic
factors is warranted. Recently miRNAs emerged as diagnostic biomarkers and
innovative therapeutic targets, while high-throughput arrays are opening new
opportunities to evaluate whether they can predict clinical outcome. The present
study evaluated whether comprehensive miRNA expression profiling correlated with
overall survival (OS) in resected PDAC patients. METHODOLOGY/PRINCIPAL FINDINGS:
High-resolution miRNA profiles were obtained with the Toray's 3D-GeneTM-miRNA
chip, detecting more than 1200 human miRNAs. RNA was successfully isolated from
paraffin-embedded primary tumors of 19 out of 26 stage-pT3N1 homogeneously
treated patients (adjuvant gemcitabine 1000 mg/m(2)/day, days-1/8/15, every 28
days), carefully selected according to their outcome (OS<12 (N = 13) vs. OS>30
months (N = 6), i.e. short/long-OS). Highly stringent statistics included t-test,
distance matrix with Spearman-ranked correlation, and iterative approaches.
Unsupervised hierarchical analysis revealed that PDACs clustered according to
their short/long-OS classification, while the feature selection algorithm RELIEF
identified the top 4 discriminating miRNAs between the two groups. These miRNAs
target more than 1500 transcripts, including 169 targeted by two or more. MiR-211
emerged as the best discriminating miRNA, with significantly higher expression in
long- vs. short-OS patients. The expression of this miRNA was subsequently
assessed by quantitative-PCR in an independent cohort of laser-microdissected
PDACs from 60 resected patients treated with the same gemcitabine regimen.
Patients with low miR-211 expression according to median value had a
significantly shorter median OS (14.8, 95%CI = 13.1-16.5, vs. 25.7 months, 95%CI
= 16.2-35.1, log-rank-P = 0.004). Multivariate analysis demonstrated that low miR
211 expression was an independent factor of poor prognosis (hazard ratio 2.3, P =
0.03) after adjusting for all the factors influencing outcome.
CONCLUSIONS/SIGNIFICANCE: Through comprehensive microarray analysis and PCR
validation we identified miR-211 as a prognostic factor in resected PDAC. These
results prompt further prospective studies and research on the biological role of
miR-211 in PDAC.
PMID- 23155458
TI - Fertilization is not a new beginning: the relationship between sperm longevity
and offspring performance.
AB - Sperm are the most diverse cell type known: varying not only among- and within-
species, but also among- and within-ejaculates of a single male. Recently, the
causes and consequences of variability in sperm phenotypes have received much
attention, but the importance of within-ejaculate variability remains largely
unknown. Correlative evidence suggests that reduced within-ejaculate variation in
sperm phenotype increases a male's fertilization success in competitive
conditions; but the transgenerational consequences of within-ejaculate variation
in sperm phenotype remain relatively unexplored. Here we examine the relationship
between sperm longevity and offspring performance in a marine invertebrate with
external fertilization, Styela plicata. Offspring sired by longer-lived sperm had
higher performance compared to offspring sired by freshly-extracted sperm of the
same ejaculate, both in the laboratory and the field. This indicates that within
ejaculate differences in sperm longevity can influence offspring fitness - a
source of variability in offspring phenotypes that has not previously been
considered. Links between sperm phenotype and offspring performance may constrain
responses to selection on either sperm or offspring traits, with broad ecological
and evolutionary implications.
PMID- 23155459
TI - A sex difference in the predisposition for physical competition: males play
sports much more than females even in the contemporary U.S.
AB - Much evidence indicates that men experienced an evolutionary history of physical
competition, both one-on-one and in coalitions. We thus hypothesized that,
compared to girls and women, boys and men will possess a greater motivational
predisposition to be interested in sports, especially team sports. According to
most scholars, advocacy groups, and the United States courts, however, this
hypothesis is challenged by modest sex differences in organized school sports
participation in the contemporary U.S., where females comprise 42% of high school
participants and 43% of intercollegiate participants. We conducted three studies
to test whether organized school sports participation data underestimate the
actual sex difference in sports participation. Study 1 analyzed the American Time
Use Survey, which interviewed 112,000 individuals regarding their activities
during one day. Females accounted for 51% of exercise (i.e., non-competitive)
participations, 24% of total sports participations, and 20% of team sports
participations. These sex differences were similar for older and younger age
groups. Study 2 was based on systematic observations of sports and exercise at 41
public parks in four states. Females accounted for 37% of exercise
participations, 19% of individual sports participations, and 10% of team sports
participations. Study 3 involved surveying colleges and universities about
intramural sports, which primarily consist of undergraduate participation in team
sports. Across 34 institutions, females accounted for 26% of registrations. Nine
institutions provided historical data, and these did not indicate that the sex
difference is diminishing. Therefore, although efforts to ensure more equitable
access to sports in the U.S. (i.e., Title IX) have produced many benefits,
patterns of sports participation do not challenge the hypothesis of a large sex
difference in interest and participation in physical competition.
PMID- 23155460
TI - Identifying gender-preferred communication styles within online cancer
communities: a retrospective, longitudinal analysis.
AB - BACKGROUND: The goal of this research is to determine if different gender
preferred social styles can be observed within the user interactions at an online
cancer community. To achieve this goal, we identify and measure variables that
pertain to each gender-specific social style. METHODS AND FINDINGS: We perform
social network and statistical analysis on the communication flow of 8,388
members at six different cancer forums over eight years. Kruskal-Wallis tests
were conducted to measure the difference between the number of intimate (and
highly intimate) dyads, relationship length, and number of communications. We
determine that two patients are more likely to form an intimate bond on a gender
specific cancer forum (ovarian P = <0.0001, breast P = 0.0089, prostate P =
0.0021). Two female patients are more likely to form a highly intimate bond on a
female-specific cancer forum (Ovarian P<0.0001, Breast P<0.01). Typically a male
patient communicates with more members than a female patient (Ovarian forum P =
0.0406, Breast forum P = 0.0013). A relationship between two patients is longer
on the gender-specific cancer forums than a connection between two members not
identified as patients (ovarian forum P = 0.00406, breast forum P = 0.00013,
prostate forum P = .0.0003). CONCLUSION: The high level of interconnectedness
among the prostate patients supports the hypothesis that men prefer to socialize
in large, interconnected, less-intimate groups. A female patient is more likely
to form a highly intimate connection with another female patient; this finding is
consistent with the hypothesis that woman prefer fewer, more intimate
connections. The relationships of same-gender cancer patients last longer than
other relationships; this finding demonstrates homophily within these online
communities. Our findings regarding online communication preferences are in
agreement with research findings from person-to-person communication preference
studies. These findings should be considered when designing online communities as
well as designing and evaluating psychosocial and educational interventions for
cancer patients.
PMID- 23155461
TI - Mobile phones in a traffic flow: a geographical perspective to evening rush hour
traffic analysis using call detail records.
AB - Excessive land use and suburbanisation around densely populated urban areas has
gone hand in hand with a growth in overall transportation and discussions about
causality of traffic congestions. The objective of this paper is to gain new
insight regarding the composition of traffic flows, and to reveal how and to what
extent suburbanites' travelling affects rush hour traffic. We put forward an
alternative methodological approach using call detail records of mobile phones to
assess the composition of traffic flows during the evening rush hour in Tallinn,
Estonia. We found that daily commuting and suburbanites influence transportation
demand by amplifying the evening rush hour traffic, although daily commuting
trips comprises only 31% of all movement at that time. The geography of the
Friday evening rush hour is distinctive from other working days, presumably in
connection with domestic tourism and leisure time activities. This suggests that
the rise of the overall mobility of individuals due to societal changes may play
a greater role in evening rush hour traffic conditions than does the impact of
suburbanisation.
PMID- 23155462
TI - Environmental enrichment reduces signs of boredom in caged mink.
AB - Animals housed in impoverished cages are often labelled 'bored'. They have also
been called 'apathetic' or 'depressed', particularly when profoundly inactive.
However, these terms are rarely operationally defined and validated. As a
negative state caused by under-stimulation, boredom should increase interest in
stimuli of all kinds. Apathy (lack of interest), by contrast, should manifest as
decreased interest in all stimuli, while anhedonia (loss of pleasure, a
depressive symptom) should specifically decrease interest in normally rewarding
stimuli. We tested the hypotheses that mink, a model carnivore, experience more
boredom, depression-like apathy, or anhedonia in non-enriched (NE) cages than in
complex, enriched (E) cages. We exposed 29 subjects (13 E, 16 NE) to ten stimuli
categorized a priori as aversive (e.g. air puffs), rewarding (e.g. evoking
chasing) or ambiguous/neutral (e.g. candles). Interest in stimuli was assessed
via latencies to contact, contact durations, and durations oriented to stimuli.
NE mink contacted all stimuli faster (P = 0.003) than E mink, and spent longer
oriented to/in contact with them, albeit only significantly so for ambiguous ones
(treatment*type P<0.013). With stimulus category removed from statistical models,
interest in all stimuli was consistently higher among NE mink (P<0.0001 for all
measures). NE mink also consumed more food rewards (P = 0.037). Finally, we
investigated whether lying down while awake and stereotypic behaviour (both
increased by NE housing) predicted these responses. Lying awake positively co
varied with certain measures of increased exploration. In contrast, stereotypic
'scrabbling' or locomotion (e.g. pacing) did not. Overall, NE mink showed no
evidence of apathy or depression, but instead a heightened investigation of
diverse stimuli consistent with boredom. This state was potentially indicated by
spending much time lying still but awake (although this result requires
replication). Boredom can thus be operationalized and assessed empirically in non
human animals. It can also be reduced by environmental enrichment.
PMID- 23155463
TI - PLK1 interacts and phosphorylates Axin that is essential for proper centrosome
formation.
AB - Abnormal amplification of centrosomes could lead to improper chromosome
segregation and aneuploidy and is implicated in cancer development. Here, we
demonstrate that Axin, a scaffolding protein in Wnt signaling, is phosphorylated
by PLK1 during mitosis. Phosphorylation of Axin Ser-157 by PLK1 abolished Axin
association with gamma-tubulin, while substitution of Ser-157 with alanine
exhibited sustained interaction with gamma-tubulin. In addition, overexpression
of Axin-S157A significantly increased the number of cells with multi-centrosomes.
These results suggest that the phosphorylation status of Axin, mediated by PLK1,
dynamically regulates its association with gamma-tubulin and centrosome formation
and segregation.
PMID- 23155464
TI - Demographic consequences of poison-related mortality in a threatened bird of
prey.
AB - Evidence for decline or threat of wild populations typically comes from multiple
sources and methods that allow optimal integration of the available information,
representing a major advance in planning management actions. We used integrated
population modelling and perturbation analyses to assess the demographic
consequences of the illegal use of poison for an insular population of Red Kites,
Milvus milvus. We first pooled into a single statistical framework the annual
census of breeding pairs, the available individual-based data, the average
productivity and the number of birds admitted annually to the local
rehabilitation centre. By combining these four types of information we were able
to increase estimate precision and to obtain an estimate of the proportion of
breeding adults, an important parameter that was not directly measured in the
field and that is often difficult to assess. Subsequently, we used perturbation
analyses to measure the expected change in the population growth rate due to a
change in poison-related mortality. We found that poison accounted for 0.43 to
0.76 of the total mortality, for yearlings and older birds, respectively. Results
from the deterministic population model indicated that this mortality suppressed
the population growth rate by 20%. Despite this, the population was estimated to
increase, albeit slowly. This positive trend was likely maintained by a very high
productivity (1.83 fledglings per breeding pair) possibly promoted by
supplementary feeding, a situation which is likely to be common to many large
obligate or facultative European scavengers. Under this hypothetical scenario of
double societal costs (poisoning of a threatened species and feeding programs),
increasing poison control would help to lower the public cost of maintaining
supplementary feeding stations.
PMID- 23155465
TI - Formalization, annotation and analysis of diverse drug and probe screening assay
datasets using the BioAssay Ontology (BAO).
AB - Huge amounts of high-throughput screening (HTS) data for probe and drug
development projects are being generated in the pharmaceutical industry and more
recently in the public sector. The resulting experimental datasets are
increasingly being disseminated via publically accessible repositories. However,
existing repositories lack sufficient metadata to describe the experiments and
are often difficult to navigate by non-experts. The lack of standardized
descriptions and semantics of biological assays and screening results hinder
targeted data retrieval, integration, aggregation, and analyses across different
HTS datasets, for example to infer mechanisms of action of small molecule
perturbagens. To address these limitations, we created the BioAssay Ontology
(BAO). BAO has been developed with a focus on data integration and analysis
enabling the classification of assays and screening results by concepts that
relate to format, assay design, technology, target, and endpoint. Previously, we
reported on the higher-level design of BAO and on the semantic querying
capabilities offered by the ontology-indexed triple store of HTS data. Here, we
report on our detailed design, annotation pipeline, substantially enlarged
annotation knowledgebase, and analysis results. We used BAO to annotate assays
from the largest public HTS data repository, PubChem, and demonstrate its utility
to categorize and analyze diverse HTS results from numerous experiments. BAO is
publically available from the NCBO BioPortal at
http://bioportal.bioontology.org/ontologies/1533. BAO provides controlled
terminology and uniform scope to report probe and drug discovery screening assays
and results. BAO leverages description logic to formalize the domain knowledge
and facilitate the semantic integration with diverse other resources. As a
consequence, BAO offers the potential to infer new knowledge from a corpus of
assay results, for example molecular mechanisms of action of perturbagens.
PMID- 23155467
TI - Probabilistic prediction of contacts in protein-ligand complexes.
AB - We introduce a statistical method for evaluating atomic level 3D interaction
patterns of protein-ligand contacts. Such patterns can be used for fast
separation of likely ligand and ligand binding site combinations out of all those
that are geometrically possible. The practical purpose of this probabilistic
method is for molecular docking and scoring, as an essential part of a scoring
function. Probabilities of interaction patterns are calculated conditional on
structural x-ray data and predefined chemical classification of molecular
fragment types. Spatial coordinates of atoms are modeled using a Bayesian
statistical framework with parametric 3D probability densities. The parameters
are given distributions a priori, which provides the possibility to update the
densities of model parameters with new structural data and use the parameter
estimates to create a contact hierarchy. The contact preferences can be defined
for any spatial area around a specified type of fragment. We compared calculated
contact point hierarchies with the number of contact atoms found near the contact
point in a reference set of x-ray data, and found that these were in general in a
close agreement. Additionally, using substrate binding site in cathechol-O
methyltransferase and 27 small potential binder molecules, it was demonstrated
that these probabilities together with auxiliary parameters separate well ligands
from decoys (true positive rate 0.75, false positive rate 0). A particularly
useful feature of the proposed Bayesian framework is that it also characterizes
predictive uncertainty in terms of probabilities, which have an intuitive
interpretation from the applied perspective.
PMID- 23155466
TI - Islet-specific CTL cloned from a type 1 diabetes patient cause beta-cell
destruction after engraftment into HLA-A2 transgenic NOD/scid/IL2RG null mice.
AB - Despite increasing evidence that autoreactive CD8 T-cells are involved in both
the initiation of type 1 diabetes (T1D) and the destruction of beta-cells, direct
evidence for their destructive role in-vivo is lacking. To address a destructive
role for autoreactive CD8 T-cells in human disease, we assessed the pathogenicity
of a CD8 T-cell clone derived from a T1D donor and specific for an HLA-A2
restricted epitope of islet-specific glucose-6-phosphatase catalytic-subunit
related protein (IGRP). HLA-A2/IGRP tetramer staining revealed a higher frequency
of IGRP-specific CD8 T-cells in the peripheral blood of recent onset human
individuals than of healthy donors. IGRP(265-273)-specific CD8 T-cells that were
cloned from the peripheral blood of a recent onset T1D individual were shown to
secrete IFNgamma and Granzyme B after antigen-specific activation and lyse HLA-A2
expressing murine islets in-vitro. Lytic capacity was also demonstrated in-vivo
by specific killing of peptide-pulsed target cells. Using the HLA-A2 NOD-scid
IL2rgamma(null) mouse model, HLA-A2-restricted IGRP-specific CD8 T-cells induced
a destructive insulitis. Together, this is the first evidence that human HLA
restricted autoreactive CD8 T-cells target HLA-expressing beta-cells in-vivo,
demonstrating the translational value of humanized mice to study mechanisms of
disease and therapeutic intervention strategies.
PMID- 23155468
TI - Human breast cancer cells are redirected to mammary epithelial cells upon
interaction with the regenerating mammary gland microenvironment in-vivo.
AB - Breast cancer is the second leading cause of cancer deaths in the United States.
At present, the etiology of breast cancer is unknown; however the possibility of
a distinct cell of origin, i.e. a cancer stem cell, is a heavily investigated
area of research. Influencing signals from the tissue niche are known to affect
stem cells. Literature has shown that cancer cells lose their tumorigenic
potential and display 'normal' behavior when placed into 'normal' ontogenic
environments. Therefore, it may be the case that the tissue microenvironment is
able to generate signals to redirect cancer cell fate. Previously, we showed that
pluripotent human embryonal carcinoma cells could be redirected by the
regenerating mammary gland microenvironment to contribute epithelial progeny for
'normal' gland development in-vivo. Here, we show that that human metastatic, non
metastatic, and metastasis-suppressed breast cancer cells proliferate and
contribute to normal mammary gland development in-vivo without tumor formation.
Immunochemistry for human-specific mitochondria, keratin 8 and 14, as well as
human-specific milk proteins (alpha-lactalbumin, impregnated transplant hosts)
confirmed the presence of human cell progeny. Features consistent with normal
mammary gland development as seen in intact hosts (duct, lumen formation,
development of secretory acini) were recapitulated in both primary and secondary
outgrowths from chimeric implants. These results suggest the dominance of the
tissue microenvironment over cancer cell fate. This work demonstrates that
cultured human breast cancer cells (metastatic and non-metastatic) respond
developmentally to signals generated by the mouse mammary gland microenvironment
during gland regeneration in-vivo.
PMID- 23155469
TI - Sotos syndrome is associated with deregulation of the MAPK/ERK-signaling pathway.
AB - Sotos syndrome (SoS) is characterized by tall stature, characteristic
craniofacial features and mental retardation. It is caused by haploinsufficiency
of the NSD1 gene. In this study, our objective was to identify downstream
effectors of NSD1 and to map these effectors in signaling pathways associated
with growth. Genome-wide expression studies were performed on dermal fibroblasts
from SoS patients with a confirmed NSD1 abnormality. To substantiate those
results, phosphorylation, siRNA and transfection experiments were performed. A
significant association was demonstrated with the Mitogen-Activated Protein
Kinase (MAPK) pathway. Members of the fibroblast growth factor family such as
FGF4 and FGF13 contributed strongly to the differential expression in this
pathway. In addition, a diminished activity state of the MAPK/ERK pathway was
demonstrated in SoS. The Ras Interacting Protein 1 (RASIP1) was identified to
exhibit upregulated expression in SoS. It was shown that RASIP1 dose-dependently
potentiated bFGF induced expression of the MAPK responsive SBE reporter providing
further support for a link between NSD1 and the MAPK/ERK signaling pathway.
Additionally, we demonstrated NSD1 expression in the terminally differentiated
hypertrophic chondrocytes of normal human epiphyseal growth plates. In short
stature syndromes such as hypochondroplasia and Noonan syndrome, the activation
level of the FGF-MAPK/ERK-pathway in epiphyseal growth plates is a determining
factor for statural growth. In analogy, we propose that deregulation of the
MAPK/ERK pathway in SoS results in altered hypertrophic differentiation of NSD1
expressing chondrocytes and may be a determining factor in statural overgrowth
and accelerated skeletal maturation in SoS.
PMID- 23155470
TI - Quiescent fibroblasts are more active in mounting robust inflammatory responses
than proliferative fibroblasts.
AB - Quiescent cells are considered to be dormant. However, recent studies suggest
that quiescent fibroblasts possess active metabolic profile and certain
functional characteristics. We previously observed that serum-starved quiescent
fibroblasts respond to proinflammatory stimuli by robust expression of
cyclooxygenase-2 (COX-2), which declines after the quiescent fibroblasts are
driven to proliferation. In this study, we elucidated the underlying signaling
and transcriptional mechanism and identified by microarray genes with similar
differential expression. By using pharmacological inhibitors coupled with gene
silencing, we uncovered the key role of protein kinase C delta (PKCdelta) and
extracellular signal regulated protein kinase 1/2 (ERK1/2) signaling in mediating
COX-2 expression in quiescent cells. Surprisingly, COX-2 expression in
proliferative cells was not blocked by PKCdelta or ERK1/2 inhibitors due to
intrinsic inhibition of PKCdelta and ERK1/2 in proliferative cells. Restrained
COX-2 transcription in proliferative cells was attributable to reduced NF-kappaB
binding. Microarray analysis identified 35 genes whose expressions were more
robust in quiescent than in proliferative cells. A majority of those genes belong
to proinflammatory cytokines, chemokines, adhesive molecules and
metalloproteinases, which require NF-kappaB for transcription. Quiescent
fibroblasts had a higher migratory activity than proliferative fibroblasts as
determined by the transwell assay. Selective COX-2 inhibition reduced migration
which was restored by prostaglandin E(2). As COX-2 and inflammatory mediators
induce DNA oxidation, we measured 8-hydroxydeoxyguanosine (8-OHdG) in quiescent
vs. proliferative fibroblasts. PMA-induced 8-OHdG accumulation was significantly
higher in quiescent than in proliferative fibroblasts. These findings indicate
that quiescent fibroblasts (and probably other quiescent cells) are at the
forefront in mounting inflammatory responses through expression of an array of
proinflammatory genes via the PKCdelta/ERK1/2 signaling pathway.
PMID- 23155471
TI - Acute ethanol exposure increases the susceptibility of the donor hearts to
ischemia/reperfusion injury after transplantation in rats.
AB - BACKGROUND: Many donor organs come from youths involved in alcohol-related
accidental death. The use of cardiac allografts for transplantation from donors
after acute poisoning is still under discussion while acute ethanol intoxication
is associated with myocardial functional and morphological changes. The aims of
this work were 1) to evaluate in rats the time-course cardiac effects of acute
ethanol-exposure and 2) to explore how its abuse by donors might affect
recipients in cardiac pump function after transplantation. METHODS: Rats received
saline or ethanol (3.45 g/kg, ip). We evaluated both the mechanical and
electrical aspects of cardiac function 1 h, 6 h or 24 h after injection. Plasma
cardiac troponin-T and glucose-levels were measured and histological examination
of the myocardium was performed. In addition, heart transplantation was
performed, in which donors received ethanol 6 h or 24 h prior to explantation.
Graft function was measured 1 h or 24 h after transplantation. Myocardial TBARS
concentration was measured; mRNA and protein expression was assessed by
quantitative real-time PCR and Western blot, respectively. RESULTS: Ethanol
administration resulted in decreased load-dependent (-34 +/- 9%) and load
independent (-33 +/- 12%) contractility parameters, LV end-diastolic pressure and
elevated blood glucose levels at 1 h, which were reversed to the level of
controls after 6 h and 24 h. In contrast to systolic dysfunction, active
relaxation and passive stiffness are slowly recovered or sustained during 24 h.
Moreover, troponin-T-levels were increased at 1 h, 6 h and 24 h after ethanol
injection. ST-segment elevation (+47 +/- 10%), elongated QT-interval (+38 +/-
4%), enlarged cardiomyocyte, DNA-strand breaks, increased both mRNA and protein
levels of superoxide dismutase-1, glutathione peroxydase-4, cytochrome-c-oxidase
and metalloproteinase-9 were observed 24 h following ethanol-exposure. After
heart transplantation, decreased myocardial contractility and relaxation,
oxidative stress and altered protein expression were observed. CONCLUSIONS: These
results demonstrate acute alcohol abuse increases the susceptibility of donor
hearts to ischemia/reperfusion in a rat heart transplant model even though the
global contractile function recovers 6 h after ethanol-administration.
PMID- 23155472
TI - Transcriptome profiling analysis reveals that flavonoid and ascorbate-glutathione
cycle are important during anther development in Upland cotton.
AB - BACKGROUND: Previous transcriptome profiling studies have investigated the
molecular mechanisms of pollen and anther development, and identified many genes
involved in these processes. However, only 51 anther ESTs of Upland cotton
(Gossypium hirsutum) were found in NCBI and there have been no reports of
transcriptome profiling analyzing anther development in Upland cotton, a major
fiber crop in the word. METHODOLOGY/PRINCIPAL FINDING: Ninety-eight hundred and
ninety-six high quality ESTs were sequenced from their 3'-ends and assembled into
6,643 unigenes from a normalized, full-length anther cDNA library of Upland
cotton. Combined with previous sequenced anther-related ESTs, 12,244 unigenes
were generated as the reference genes for digital gene expression (DGE) analysis.
The DGE was conducted on anthers that were isolated at tetrad pollen (TTP),
uninucleate pollen (UNP), binucleate pollen (BNP) and mature pollen (MTP) periods
along with four other tissues, i.e., roots (RO), stems (ST), leaves (LV) and
embryos (EB). Through transcriptome profiling analysis, we identified 1,165 genes
that were enriched at certain anther development periods, and many of them were
involved in starch and sucrose metabolism, pentose and glucuronate
interconversion, flavonoid biosynthesis, and ascorbate and aldarate metabolism.
CONCLUSIONS/SIGNIFICANCE: We first generated a normalized, full-length cDNA
library from anthers and performed transcriptome profiling analysis of anther
development in Upland cotton. From these results, 10,178 anther expressed genes
were identified, among which 1,165 genes were stage-enriched in anthers. And many
of these stage-enriched genes were involved in some important processes
regulating anther development.
PMID- 23155473
TI - Linking personality to larval energy reserves in rainbow trout (Oncorhynchus
mykiss).
AB - There is a surging interest in the evolution, ecology and physiology of
personality differences. However, most of the studies in this research area have
been performed in adult animals. Trait variations expressed early in development
and how they are related to the ontogeny of an animal's personality are far less
studied. Genetic differences as well as environmental factors causing functional
variability of the central serotonergic system have been related to personality
differences in vertebrates, including humans. Such gene-environment interplay
suggests that the central serotonergic system plays an important role in the
ontogeny of personality traits. In salmonid fishes, the timing of emergence from
spawning nests is related to energy reserves, aggression, and social dominance.
However, it is currently unknown how the size of the yolk reserve is reflected on
aggression and dominance, or if these traits are linked to differences in
serotonergic transmission in newly emerged larvae. In this study we investigated
the relationship between yolk reserves, social dominance, and serotonergic
transmission in newly emerged rainbow trout (Oncorhynchus mykiss) larvae. This
was conducted by allowing larvae with the same emergence time, but with different
yolk sizes, to interact in pairs for 24 h. The results show that individuals with
larger yolks performed more aggressive acts, resulting in a suppression of
aggression in individuals with smaller yolks. A higher brain serotonergic
activity confirmed subordination in larvae with small yolks. The relationship
between social dominance and yolk size was present in siblings, demonstrating a
link between interfamily variation in energy reserves and aggression, and
suggests that larger yolk reserves fuel a more aggressive personality during the
initial territorial establishment in salmonid fishes. Furthermore, socially naive
larvae with big yolks had lower serotonin levels, suggesting that other factors
than the social environment causes variation in serotonergic transmission,
underlying individual variation in aggressive behavior.
PMID- 23155474
TI - Toward the beginning of time: circadian rhythms in metabolism precede rhythms in
clock gene expression in mouse embryonic stem cells.
AB - The appearance, progression, and potential role for circadian rhythms during
early development have previously focused mainly on the suprachiasmatic nucleus
(SCN) and peri- and postnatal expression of canonical clock genes. More recently,
gene expression studies in embryonic stem cells have shown that some clock genes
are expressed in undifferentiated cells; however rhythmicity was only established
when cells are directed toward a neural fate. These studies also concluded that a
functional clock is not present in ESCs, based solely on their gene expression.
The null hypothesis underlying the present study is that embryonic stem cells
become rhythmic in both clock gene expression and glucose utilization only when
allowed to spontaneously differentiate. Undifferentiated stem cells (ESCs, n = 6
cultures/timepoint for all experiments) were either maintained in their
pluripotent state or released into differentiation (dESCs, n = 6
cultures/timepoint for all experiments). Glucose utilization was assayed through
2-deoxyglucose uptake measurement, and clock gene and glucose transporter
expression was assayed every 4 hours for 2 days in ESCs and dESCs by quantitative
PCR (qPCR) in the same cell lysates. Undifferentiated stem cells expressed a self
sustained rhythm in glucose uptake that was not coincident with rhythmic
expression of clock genes. This physiological rhythm was paralleled by glucose
transporter mRNA expression. Upon differentiation, circadian patterns of some but
not all clock genes were expressed, and the amplitude of the glucose utilization
rhythm was enhanced in dESCs. These data provide the earliest evidence of a
functional circadian clock, in addition to further challenging the idea that
rhythmic transcription of clock genes are necessary for rhythmic physiological
output and suggest a role for a clock-controlled physiology in the earliest
stages of development.
PMID- 23155475
TI - Neutrophil elastase alters the murine gut microbiota resulting in enhanced
Salmonella colonization.
AB - The intestinal microbiota has been found to play a central role in the
colonization of Salmonella enterica serovar Typhimurium in the gastrointestinal
tract. In this study, we present a novel process through which Salmonella benefit
from inflammatory induced changes in the microbiota in order to facilitate
disease. We show that Salmonella infection in mice causes recruitment of
neutrophils to the gut lumen, resulting in significant changes in the composition
of the intestinal microbiota. This occurs through the production of the enzyme
elastase by neutrophils. Administration of recombinant neutrophil elastase to
infected animals under conditions that do not elicit neutrophil recruitment
caused shifts in microbiota composition that favored Salmonella colonization,
while inhibition of neutrophil elastase reduced colonization. This study reveals
a new relationship between the microbiota and the host during infection.
PMID- 23155477
TI - LETTER TO THE EDITOR Correction of Tethered Tracheostomy Scar Using Dermofat
Graft.
PMID- 23155478
TI - Transmission of Ebola virus from pigs to non-human primates.
AB - Ebola viruses (EBOV) cause often fatal hemorrhagic fever in several species of
simian primates including human. While fruit bats are considered natural
reservoir, involvement of other species in EBOV transmission is unclear. In 2009,
Reston-EBOV was the first EBOV detected in swine with indicated transmission to
humans. In-contact transmission of Zaire-EBOV (ZEBOV) between pigs was
demonstrated experimentally. Here we show ZEBOV transmission from pigs to
cynomolgus macaques without direct contact. Interestingly, transmission between
macaques in similar housing conditions was never observed. Piglets inoculated oro
nasally with ZEBOV were transferred to the room housing macaques in an open
inaccessible cage system. All macaques became infected. Infectious virus was
detected in oro-nasal swabs of piglets, and in blood, swabs, and tissues of
macaques. This is the first report of experimental interspecies virus
transmission, with the macaques also used as a human surrogate. Our finding may
influence prevention and control measures during EBOV outbreaks.
PMID- 23155476
TI - Expression profile in rice panicle: insights into heat response mechanism at
reproductive stage.
AB - Rice at reproductive stage is more sensitive to environmental changes, and little
is known about the mechanism of heat response in rice panicle. Here, using rice
microarray, we provided a time course gene expression profile of rice panicle at
anther developmental stage 8 after 40 degrees C treatment for 0 min, 20 min, 60
min, 2 h, 4 h, and 8 h. The identified differentially expressed genes were mainly
involved in transcriptional regulation, transport, cellular homeostasis, and
stress response. The predominant transcription factor gene families responsive to
heat stress were Hsf, NAC, AP2/ERF, WRKY, MYB, and C(2)H(2). KMC analysis
discovered the time-dependent gene expression pattern under heat stress. The
motif co-occurrence analysis on the promoters of genes from an early up-regulated
cluster showed the important roles of GCC box, HSE, ABRE, and CE3 in response to
heat stress. The regulation model central to ROS combined with transcriptome and
ROS quantification data in rice panicle indicated the great importance to
maintain ROS balance and the existence of wide cross-talk in heat response. The
present study increased our understanding of the heat response in rice panicle
and provided good candidate genes for crop improvement.
PMID- 23155479
TI - Neural correlates of lyrical improvisation: an FMRI study of freestyle rap.
AB - The neural correlates of creativity are poorly understood. Freestyle rap provides
a unique opportunity to study spontaneous lyrical improvisation, a
multidimensional form of creativity at the interface of music and language. Here
we use functional magnetic resonance imaging to characterize this process. Task
contrast analyses indicate that improvised performance is characterized by
dissociated activity in medial and dorsolateral prefrontal cortices, providing a
context in which stimulus-independent behaviors may unfold in the absence of
conscious monitoring and volitional control. Connectivity analyses reveal
widespread improvisation-related correlations between medial prefrontal,
cingulate motor, perisylvian cortices and amygdala, suggesting the emergence of a
network linking motivation, language, affect and movement. Lyrical improvisation
appears to be characterized by altered relationships between regions coupling
intention and action, in which conventional executive control may be bypassed and
motor control directed by cingulate motor mechanisms. These functional
reorganizations may facilitate the initial improvisatory phase of creative
behavior.
PMID- 23155480
TI - Development of miniaturized walking biological machines.
AB - The quest to 'forward-engineer' and fabricate biological machines remains a grand
challenge. Towards this end, we have fabricated locomotive "bio-bots" from
hydrogels and cardiomyocytes using a 3D printer. The multi-material bio-bot
consisted of a 'biological bimorph' cantilever structure as the actuator to power
the bio-bot, and a base structure to define the asymmetric shape for locomotion.
The cantilever structure was seeded with a sheet of contractile cardiomyocytes.
We evaluated the locomotive mechanisms of several designs of bio-bots by changing
the cantilever thickness. The bio-bot that demonstrated the most efficient
mechanism of locomotion maximized the use of contractile forces for overcoming
friction of the supporting leg, while preventing backward movement of the
actuating leg upon relaxation. The maximum recorded velocity of the bio-bot was
~236 um s(-1), with an average displacement per power stroke of ~354 um and
average beating frequency of ~1.5 Hz.
PMID- 23155481
TI - New thermodynamical force in plasma phase space that controls turbulence and
turbulent transport.
AB - Physics of turbulence and turbulent transport has been developed on the central
dogma that spatial gradients constitute the controlling parameters, such as
Reynolds number and Rayleigh number. Recent experiments with the nonequilibrium
plasmas in magnetic confinement devices, however, have shown that the turbulence
and transport change much faster than global parameters, after an abrupt change
of heating power. Here we propose a theory of turbulence in inhomogeneous
magnetized plasmas, showing that the heating power directly influences the
turbulence. New mechanism, that an external source couples with plasma
fluctuations in phase space so as to affect turbulence, is investigated. A new
thermodynamical force in phase-space, i.e., the derivative of heating power by
plasma pressure, plays the role of new control parameter, in addition to spatial
gradients. Following the change of turbulence, turbulent transport is modified
accordingly. The condition under which this new effect can be observed is also
evaluated.
PMID- 23155482
TI - Initial geometries, interaction mechanism and high stability of silicene on
Ag(111) surface.
AB - Using ab initio methods, we have investigated the structures and stabilities of
Si(N) clusters (N <= 24) on Ag(111) surface as the initial stage of silicene
growth. Unlike the dome-shaped graphene clusters, Si clusters prefer nearly flat
structures with low buckling, more stable than directly deposition of the 3D
freestanding Si clusters on Ag surface. The p-d hybridization between Ag and Si
is revealed as well as sp(2) characteristics in Si(N)@Ag(111). Three types of
silicene superstructures on Ag(111) surface have been considered and the
simulated STM images are compared with experimental observations. Molecular
dynamic simulations show high thermal stability of silicene on Ag(111) surfaces,
contrast to that on Rh(111). The present theoretical results constitute a
comprehensive picture about the interaction mechanism of silicene on Ag(111)
surface and explain the superiority of Ag substrate for silicene growth, which
would be helpful for improving the experimentally epitaxial growth of silicene.
PMID- 23155483
TI - Correlative light and electron microscopy using cathodoluminescence from
nanoparticles with distinguishable colours.
AB - Correlative light and electron microscopy promises to combine molecular
specificity with nanoscale imaging resolution. However, there are substantial
technical challenges including reliable co-registration of optical and electron
images, and rapid optical signal degradation under electron beam irradiation.
Here, we introduce a new approach to solve these problems: imaging of stable
optical cathodoluminescence emitted in a scanning electron microscope by
nanoparticles with controllable surface chemistry. We demonstrate well-correlated
cathodoluminescence and secondary electron images using three species of
semiconductor nanoparticles that contain defects providing stable, spectrally
distinguishable cathodoluminescence. We also demonstrate reliable surface
functionalization of the particles. The results pave the way for the use of such
nanoparticles for targeted labeling of surfaces to provide nanoscale mapping of
molecular composition, indicated by cathodoluminescence colour, simultaneously
acquired with structural electron images in a single instrument.
PMID- 23155484
TI - Ribosomal frameshifting used in influenza A virus expression occurs within the
sequence UCC_UUU_CGU and is in the +1 direction.
AB - Programmed ribosomal frameshifting is used in the expression of many virus genes
and some cellular genes. In eukaryotic systems, the most well-characterized
mechanism involves -1 tandem tRNA slippage on an X_XXY_YYZ motif. By contrast,
the mechanisms involved in programmed +1 (or -2) slippage are more varied and
often poorly characterized. Recently, a novel gene, PA-X, was discovered in
influenza A virus and found to be expressed via a shift to the +1 reading frame.
Here, we identify, by mass spectrometric analysis, both the site (UCC_UUU_CGU)
and direction (+1) of the frameshifting that is involved in PA-X expression.
Related sites are identified in other virus genes that have previously been
proposed to be expressed via +1 frameshifting. As these viruses infect insects
(chronic bee paralysis virus), plants (fijiviruses and amalgamaviruses) and
vertebrates (influenza A virus), such motifs may form a new class of +1
frameshift-inducing sequences that are active in diverse eukaryotes.
PMID- 23155485
TI - A Type III restriction-modification system in Mycoplasma mycoides subsp. capri.
AB - The sequenced genome of Mycoplasma mycoides subsp. capri revealed the presence of
a Type III restriction-modification system (MmyCI). The methyltransferase
(modification) subunit of MmyCI (M.MmyCI) was shown to recognize the sequence 5'
TGAG-3' and methylate the adenine. The coding region of the methyltransferase
gene contains 12 consecutive AG dinucleotide repeats that result in a
translational termination at a TAA codon immediately beyond the repeat region.
This strain does not have MmyCI activity. A clone was found with 10 AG repeats
such that the gene is in frame, and this strain has MmyCI activity, suggesting
that the expression of the MmyCI methyltransferase may be phase variable.
PMID- 23155486
TI - Mechanistic and structural basis for inhibition of thymidylate synthase ThyX.
AB - Nature has established two mechanistically and structurally unrelated families of
thymidylate synthases that produce de novo thymidylate or dTMP, an essential DNA
precursor. Representatives of the alternative flavin-dependent thymidylate
synthase family, ThyX, are found in a large number of microbial genomes, but are
absent in humans. We have exploited the nucleotide binding pocket of ThyX
proteins to identify non-substrate-based tight-binding ThyX inhibitors that
inhibited growth of genetically modified Escherichia coli cells dependent on thyX
in a manner mimicking a genetic knockout of thymidylate synthase. We also solved
the crystal structure of a viral ThyX bound to 2-hydroxy-3-(4-methoxybenzyl)-1,4
naphthoquinone at a resolution of 2.6 A. This inhibitor was found to bind within
the conserved active site of the tetrameric ThyX enzyme, at the interface of two
monomers, partially overlapping with the dUMP binding pocket. Our studies provide
new chemical tools for investigating the ThyX reaction mechanism and establish a
novel mechanistic and structural basis for inhibition of thymidylate synthesis.
As essential ThyX proteins are found e.g. in Mycobacterium tuberculosis and
Helicobacter pylori, our studies have also potential to pave the way towards the
development of new anti-microbial compounds.
PMID- 23155488
TI - Exposure of patients to ionizing radiation. What are the risks?
PMID- 23155487
TI - Manipulation of PK-M mutually exclusive alternative splicing by antisense
oligonucleotides.
AB - Alternative splicing of the pyruvate kinase M gene involves a choice between
mutually exclusive exons 9 and 10. Use of exon 10 to generate the M2 isoform is
crucial for aerobic glycolysis (the Warburg effect) and tumour growth. We
previously demonstrated that splicing enhancer elements that activate exon 10 are
mainly found in exon 10 itself, and deleting or mutating these elements increases
the inclusion of exon 9 in cancer cells. To systematically search for new
enhancer elements in exon 10 and develop an effective pharmacological method to
force a switch from PK-M2 to PK-M1, we carried out an antisense oligonucleotide
(ASO) screen. We found potent ASOs that target a novel enhancer in exon 10 and
strongly switch the splicing of endogenous PK-M transcripts to include exon 9. We
further show that the ASO-mediated switch in alternative splicing leads to
apoptosis in glioblastoma cell lines, and this is caused by the downregulation of
PK-M2, and not by the upregulation of PK-M1. These data highlight the potential
of ASO-mediated inhibition of PK-M2 splicing as therapy for cancer.
PMID- 23155489
TI - Assessing physical activity and related correlates among adults in Hawai'i.
AB - Regular physical activity has been shown to reduce the risk of cardiovascular
disease, stroke, some mental illnesses and some cancer. Despite the well-known
benefits of physical activity, about half of the adults in the United States and
Hawai'i do not get enough. Rates of physical activity differ greatly among ethnic
groups and interventions to increase physical activity may need to be tailored
for specific ethnicities. In this study, 3,588 adults living in Hawai'i completed
a random digit dial survey on their physical activity level. Native Hawaiians and
Whites were more likely to be active than Chinese, Filipino and Japanese
respondents. Multivariate logistic regressions analyses eliminated differences
between Whites, Filipinos and Chinese respondents; however, Native Hawaiians were
still more likely to report meeting physical activity guidelines and Japanese
were less likely. Other significant predictors included being younger, male,
having a job involving heavy labor, being in the normal weight range, being in
good or excellent health, having high self-efficacy, spending less time sitting,
and walking a dog more frequently. Differences in meeting physical activity
guidelines can be used in planning future public health campaigns.
PMID- 23155490
TI - Door-to-balloon time in acute ST segment elevation myocardial infarction--further
experience.
AB - Early coronary reperfusion has been established as the optimal treatment for
acute ST segment elevation myocardial infarction. A treatment protocol,
previously described, has been designed to reduce delay in achieving
recanalization of the culprit coronary artery. Over a period of about 4 years,
Door-to-Balloon time has been analyzed for patients arriving in the Emergency
Department with this condition. During that time the process was enhanced by the
ability of ambulance personnel to transmit 12 lead EKG's from the field. Door-to
Balloon times have been analyzed and compared to the American College of
Cardiology target of 90 minutes. After just over one year of gradually improving
results, 100% compliance was achieved. From that time on, this was achieved
during the period under consideration in 97% of cases.
PMID- 23155491
TI - Inflammatory bowel disease treatment and non-melanoma skin cancer: a case report.
AB - Immunosuppressant medications for Inflammatory Bowel Disease can help with both
symptoms and disease progression. However, like immunosuppressants used in
transplant patients, they are now suspect of contributing to nonmelenoma skin
cancer (NMSC). Presented is a case of a 57-year-old Jewish man with Crohn's
Disease who was diagnosed with a total of 84 NMSCs. We hope to elucidate the risk
of immunosuppressants, particularly the thiopurines, on the development of NMSC.
PMID- 23155493
TI - Medical school hotline: the Department of Native Hawaiian Health at the John A.
Burns School of Medicine.
PMID- 23155495
TI - Pilidiella tibouchinae sp. nov. associated with foliage blight of Tibouchina
granulosa (quaresmeira) in Brazil.
AB - Tibouchina granulosa (Melastomataceae), Brazilian glorytree (Brazilian common
name - quaresmeira), a common tree of the Atlantic Forest of Brazil, is widely
used as an ornamental for its violet or pink blossoms. Little is known about
fungal diseases affecting this species, although these represent a known
limitation for its cultivation in nurseries. Among these there is a foliage
blight that occurs in combination with distortion of branch apices and die-back.
A consistent association of a species of Pilidiella with the diseased tissues was
observed. The fungus was isolated in pure culture and based on its morphology and
DNA phylogeny, we conclude that it represents a new species, for which the name
Pilidiella tibouchinae is introduced.
PMID- 23155496
TI - Reappraisal and neotypification of Phyllachora feijoae.
AB - Acca sellowiana (Myrtaceae), feijoa (in Brazil, goiaba da serra), is a native
southern South America tree that produces edible fruits which, although only
occasionally cultivated in South America, became a significant fruit crop in New
Zealand. Recently, during surveys for fungal pathogens of feijoa in southern
Brazil, several plants were found bearing tar-spot symptoms caused by a species
of Phyllachora. A literature search enabled us to identify the fungus as
Phyllachora feijoae, a little-known species originally described in the 19(th)
century by H. Rehm and later transferred to the genus Catacauma. The name
Catacauma feijoae, although now regarded as a later synonym of P. feijoae is
still mistakenly in use (as, for instance, in the Brazilian list of fungi on
plants). The type specimen was most probably deposited in the Botanisches Garten
und Museum Berlin-Dahlem (B) and lost or destroyed during World War II, and could
not be located. The recent recollection of abundant material of this fungus in
the vicinity of Pelotas (Rio Grande do Sul, Brazil) allowed its re-examination
and neotypification. Phyllachora feijoae is also illustrated here for the first
time.
PMID- 23155497
TI - Managing and coping with names of pleomorphic fungi in a period of transition.
AB - An explanation is provided of the recent changes in the International Code of
Nomenclature for algae, fungi and plants relating to the ending of the separate
naming of different states of fungi with a pleomorphic life-cycle. Issues
relating to their implementation are discussed, including problems of defining
"widely used", author citations, proofs of holomorphy, typification, the
preparation of "Lists of accepted and rejected names" (with a possible
timetable), relationship to the existing processes of sanctioning and
conservation or rejection, and steps to be considered for the future. This
material is presented here to stimulate debate on the actions that should be
taken by individuals, and responsible committees, in the current period of
transition to a system of fungal nomenclature fit for the 21(st) century.
PMID- 23155498
TI - Afrocantharellus gen. stat. nov. is part of a rich diversity of African
Cantharellaceae.
AB - A new genus in the Cantharellaceae, Afrocantharellus, is recognized based on
results from phylogenetic analyses of rDNA LSU and concatenated LSU/5.8-ITS2/ATP6
data. It was previously recognized as a subgenus, but comprehensive fieldwork and
the acquisition of numerous sequences for previously neglected African
Cantharellus species formed the basis for a reappraisal of generic and species
delimitations. Afrocantharellus is characterized morphologically by the
basidiomes having thick, distantly spaced diverging folds of variegated colour.
In contrast to most of Cantharellus, Afrocantharellus mostly lacks clamp
connections. Phylogenies of Cantharellus and Afrocantharellus based on LSU and a
concatenated data set are provided, along with descriptions of and a key to the
four species and one form of Afrocantharellus recognized. Six new combinations
are made.
PMID- 23155499
TI - The identity of Cintractia disciformis: reclassification and synonymy of a
southern Asian smut parasitic on Carex sect. Aulocystis.
AB - The identity of a neglected smut fungus, Cintractia disciformis, described from
Carex hirtella in the Western Himalaya, India is reassessed. The species is
excluded from Cintractia and is confirmed as a distinct species of Anthracoidea.
Two smuts, A. nepalensis on Carex nakaoana in Nepal, and A. haematostomae on
Carex haematostoma in China, are similar morphologically and considered to be
later heterotypic synonyms of Cintractia disciformis. The appropriate
nomenclatural combination for this species, Anthracoidea disciformis comb. nov.,
is validated.
PMID- 23155500
TI - Ceratocystis eucalypticola sp. nov. from Eucalyptus in South Africa and
comparison to global isolates from this tree.
AB - Eucalyptus trees, mostly native to Australia, are widely planted in the tropics
and Southern Hemisphere for the production of wood and pulp. Worldwide surveys of
diseases on these trees have yielded a large collection of Ceratocystis isolates
from dying trees or from wounds on their stems. The aim of this study was to
characterise these isolates and to consider their relatedness to each other.
Culture appearance, morphological features and a distinctive fruity odour in all
cultures were typical of species in the Ceratocystis fimbriatasensu lato (s.
lat.) complex. Phylogenetic analyses of sequences for the combined ITS, betat-1
and TEF1-alpha gene regions revealed a genetically diverse group of isolates
residing in a single large clade, that were distinct from all other species in
the C. fimbriatas. lat. complex. Based on morphology and phylogenetic inference,
the Eucalyptus isolates are recognised as closely related. The South African
isolates are described here as a new species, C. eucalypticola.
PMID- 23155501
TI - Aspergillus section Versicolores: nine new species and multilocus DNA sequence
based phylogeny.
AB - beta-tubulin, calmodulin, internal transcribed spacer and partial lsu-rDNA, RNA
polymerase 2, DNA replication licensing factor Mcm7, and pre-rRNA processing
protein Tsr1 were amplified and sequenced from numerous isolates belonging to
Aspergillus sect. versicolor. The isolates were analyzed phylogenetically using
the concordance model to establish species boundaries. Aspergillus
austroafricanus, A. creber, A. cvjetkovicii, A. fructus, A. jensenii, A.
puulaauensis, A. subversicolor, A. tennesseensis and A. venenatus are described
as new species and A. amoenus, A. protuberus,A. sydowii, A. tabacinus and A.
versicolor are accepted as distinct species on the basis of molecular and
phenotypic differences. PCR primer pairs used to detect A. versicolor in sick
building syndrome studies have a positive reaction for all of the newly described
species except A. subversicolor.
PMID- 23155502
TI - The impacts of the discontinuation of dual nomenclature of pleomorphic fungi: the
trivial facts, problems, and strategies.
AB - The symposium "One fungus = Which name" held in Amsterdam 12-13 April 2012,
addressed the drastic changes in the naming of pleomorphic fungi adopted by the
18(th) International Botanical Congress in Melbourne in 2011. Possible solutions
and ways to face resulting problems were suggested. The fundamental change is
that under the new rules fungi in future will be treated nomenclaturally like
plants and all other groups of organisms ruled by the ICN, i.e. with one correct
name for each species. Numerous discussions and statements during the Symposium
reflected widespread anxieties that these rules could negatively influence
taxonomic work on pleomorphic fungi. However, they are groundless, being based on
misunderstandings and confusion of nomenclature and taxonomy. With pleomorphic
fungi, taxonomists will in future have to answer the question whether different
morphs can represent one fungus (taxon), but this remains a taxonomic decision
and has nothing to do with nomenclature. Furthermore, the ICN does not and cannot
rule on how this decision is made. Thus it cannot provide rules based solely on
methods involving morphology in vivo or in vitro, molecular analyses,
physiological and biochemical data, inoculation experiments in pathogenic groups
or any other methods or combinations of them. It is up to the taxonomist to
select appropriate methods and to decide which data are sufficient to introduce
new taxa. Some future problems and strategies around the application of anamorph-
and teleomoph-typified taxon names (genera and species), are discussed here,
using the recently monographed powdery mildews (Erysiphales) as an example.
PMID- 23155503
TI - The importance of fungi and of mycology for a global development of the
bioeconomy.
AB - The vision of the European common research programme for 2014-2020, called
Horizon 2020, is to create a smarter, more sustainable and more inclusive
society. However, this is a global endeavor, which is important for mycologists
all over the world because it includes a special role for fungi and fungal
products. After ten years of research on industrial scale conversion of biowaste,
the conclusion is that the most efficient and gentle way of converting
recalcitrant lignocellulosic materials into high value products for industrial
purposes, is through the use of fungal enzymes. Moreover, fungi and fungal
products are also instrumental in producing fermented foods, to give storage
stability and improved health. Climate change will lead to increasingly severe
stress on agricultural production and productivity, and here the solution may
very well be that fungi will be brought into use as a new generation of
agricultural inoculants to provide more robust, more nutrient efficient, and more
drought tolerant crop plants. However, much more knowledge is required in order
to be able to fully exploit the potentials of fungi, to deliver what is needed
and to address the major global challenges through new biological processes,
products, and solutions. This knowledge can be obtained by studying the fungal
proteome and metabolome; the biology of fungal RNA and epigenetics; protein
expression, homologous as well as heterologous; fungal host/substrate relations;
physiology, especially of extremophiles; and, not the least, the extent of global
fungal biodiversity. We also need much more knowledge and understanding of how
fungi degrade biomass in nature.The projects in our group in Aalborg University
are examples of the basic and applied research going on to increase the
understanding of the biology of the fungal secretome and to discover new enzymes
and new molecular/bioinformatics tools.However, we need to put Mycology higher up
on global agendas, e.g. by positioning Mycology as a candidate for an OECD
Excellency Program. This could pave the way for increased funding of
international collaboration, increased global visibility, and higher priority
among decision makers all over the world.
PMID- 23155504
TI - Variation in mitochondrial genome primary sequence among whole-genome-sequenced
strains of Neurospora crassa.
AB - Eighteen classical mutant strains of Neurospora crassa were subject to whole
genome sequence analysis and the mitochondrial genome is analyzed. Overall, the
mitochondrial genomes of the classical mutant strains are 99.45 to 99.98 %
identical to the reference genome. Two-thirds of the SNPs and three-fourths of
indels identified in this analysis are shared among more than one strain. Most of
the limited variability in mitochondrial genome sequence is neutral with regard
to protein structure. Despite the fact that the mitochondrial genome is present
in multiple copies per cell, many of the polymorphisms were homozygous within
each strain. Conversely, some polymorphisms, especially those associated with
large scale rearrangements are only present in a fraction of the reads covering
each region. The impact of this variation is unknown and further studies will be
necessary to ascertain if this level of polymorphism is common among fungi and
whether it reflects the impact of ageing cultures.
PMID- 23155505
TI - The status of mycology in Africa: A document to promote awareness.
AB - The African Mycological Association (AMA) promotes mycology amongst members in
Africa and globally. The AMA has about 200 members, mostly from African states
but also with strong representation from Europe and USA, amongst others. Recent
efforts by members of the AMA focused on reviving and developing mycological
research and networking in Africa. A great deal must, however, still be done to
promote the AMA under African mycologists, and those elsewhere with interests in
Africa. African mycologists also experience challenges typical of the developing
world and a great deal of fungi still needs to be discovered. This can also be
seen as representing great opportunities for research and collaboration. Several
issues pertinent to mycology in Africa were discussed during Special Interest
Group sessions of the 9th International Mycological Congress in 2010, and through
several opinion pieces contributed by AMA members in the AMA newsletter,
MycoAfrica. This contribution serves as a document to summarise these in a form
that can be presented to fellow mycologists, biologists and other scientists,
relevant government departments, funding bodies and Non-Governmental
Organizations and that pins down the importance of mycology, the status thereof
in Africa and the need to promote it more.
PMID- 23155506
TI - FDA approves new 4-drug once-a-day HIV treatment.
PMID- 23155507
TI - Guidance. Interim recommendations released for physicians prescribing PrEP.
PMID- 23155508
TI - Report. Risky sexual behavior declines among black high schoolers.
PMID- 23155509
TI - HIV groups against CDC recommendations for PrEP.
PMID- 23155510
TI - Prisons. Rights of inmate with HIV not violated by housing decision.
PMID- 23155511
TI - Court dismisses malpractice suit for failure to provide notice.
PMID- 23155512
TI - Anonymity. Man's request to proceed with HIV suit anonymously denied.
PMID- 23155513
TI - Discrimination. Clinic chose not to hire man because of drug test, not HIV.
PMID- 23155514
TI - Bone density and depression in premenopausal South African women: a pilot study.
AB - OBJECTIVE: It is posited that the effect of depression on BMD is dependent on the
severity of depression. Conflicting evidence exists regarding this possible
association. This study investigated the association between depression and low
bone mineral density (BMD). METHODS: The hypothesis was investigated in a random
sample of volunteers (n=40) and in premenopausal female psychiatric patients
(n=5) diagnosed with recurrent severe major depression. The outcome measures were
BMD (DEXA); depression (Beck Depression Inventory and Psychological General Well
being Scale) and 24-hour saliva cortisol levels (ELISA). In a comparison of women
(4 of the 40 i.e. "control" subjects) with negligible symptoms of depression and
the five patients with severe recurrent major depression- BMD, depression, saliva
cortisol and bone turnover markers were measured and compared. Pro-inflammatory
status (IL-1 and TNF-alpha) was investigated in the psychiatric patients only.
RESULTS: In the random - non clinical - sample of women (n=40), 26 exhibited
normal BDM and 14 exhibited low BMD. Drepressive symptoms and cortisol level were
not significantly different between these two groups. Women with severe recurrent
major depression (n=5)exhibited lower median BMD T-scores, higher overall bone
turnover and higher 24-hour cortisol levels compared to "control" subjects (n=4).
The psychiatric patients also exhibited elevated IL-1 levels. CONCLUSION: The
effect of depression on BMD may be dependent on the depression severity, IL-1 and
cortisol are possible mediators in depression-induced BMD loss.
PMID- 23155515
TI - [Non technical skills for surgeons].
PMID- 23155516
TI - [Role of surgeons in the patient care team in the operating rooms: ideal surgeons
from point of view of anesthesiology].
PMID- 23155517
TI - [Importance of peer review within hospitals].
PMID- 23155518
TI - Board of International Affairs Pan-African Division quarterly newsletter: African
International Division, Royal College of Psychiatrists.
PMID- 23155520
TI - Emerging opportunities for mental health research in Africa.
PMID- 23155519
TI - Developing services for the wandering mentally ill in an African city---the Lagos
State example.
PMID- 23155521
TI - When coercion meets hope: can forensic psychiatry adopt the recovery model.
PMID- 23155523
TI - [Learning from health care system in other countries: Open Disclosure].
PMID- 23155522
TI - [Role of the Japan Surgical Society in the achievement of surgical safety by
surgeons].
PMID- 23155524
TI - [Evaluation of the practice guidelines and quality indicators].
PMID- 23155525
TI - [Practice guidelines viewed from the point of legal aspect].
PMID- 23155526
TI - [Guidelines for patients in the delivery of health care in Japan].
PMID- 23155527
TI - [Practice guidelines for treatment of cancers in Europe and United States].
PMID- 23155528
TI - [Release of the Practice Guidelines for Cancer treatment].
PMID- 23155529
TI - [Problems in the practice guidelines for treatment of cancers and future trends].
PMID- 23155530
TI - [Statistical design in clinical trials].
PMID- 23155531
TI - [Development of surgical assistance robots].
PMID- 23155532
TI - [Present condition of clinical trials in surgeries for patients with lung cancer
in Japan].
PMID- 23155533
TI - [Present condition of clinical trials in surgeries for patients with
hepatobiliary pancreatic lesion in Japan].
PMID- 23155534
TI - [Multicenter randomized controlled trial in use of the synthetic absorbable
surgical suture material for digestive system surgical procedures to prevent
surgical wound infections].
PMID- 23155535
TI - [Implementation of clinical trials in the field of surgery and the role of the
periodical "Surgery Today" published in English by the Japanese Surgical
Society].
PMID- 23155536
TI - [One hundred years of evolution of esophageal surgical approach and clinical
significance].
AB - Esophageal surgery has developed for almost 100 years. Esophagectomy can be
performed via left, right thoracotomy, even via hiatus without thoracotomy due to
its unique anatomic characteristics. Left thoracotomy was the initial approach in
the world, and has still been performed by Chinese colleagues, but Ivor Lewis
(right side thoracotomy) procedure is popular in western countries. Currently,
esophagectomy by right thoracotomy has been accepted worldwide since its radical
dissection for tumor. Therefore, video-assisted thoracoscopic esophagectomy based
on right thoracotomy will be the mainstream surgery for esophageal cancer in the
future since its minimal invasion and tumor dissection.
PMID- 23155537
TI - [Treatment of gastroesophageal reflux disease: comments from thoracic surgeon].
AB - Gastroesophageal reflux disease (GERD) is the most common gastrointestinal
diagnosis recorded during visits to outpatient clinics in west countries. The
prevalence of symptom-defined GERD in China is as high as 3% to 5%. Asa
dysfunction, GERD is characterized by reflux and heartburn. The pathophysiologic
process of GERD is very complicated and subtle. The spectrum of injury from long
term reflux of acid or bile includes damage mucosa, Barrett's esophagus,
dysplasia, and esophageal cancer. Therefore, the therapies of GERD should focus
on controlling symptom,treating complications, and surveillance the possibility
of oncologic transform. As with therapy with proton-pump inhibitors (PPI),
modifying lifestyle is another most important modality for most GERD. The window
of surgical treatment for GERD is narrow. Surgical therapy is alternative
management approach to the patients with PPI failure, complications, or huge
hernia. The laparoscopic minimally invasive procedure improves the acceptance of
patients to surgical therapy, but the long-term complication and drawbacks of
anti-reflux surgery cannot be ignored, and which is even more common than open
procedures. The limitations of current therapy for GERD have encouraged a search
for more effective treatment.The Linx sphincter augmentation device has been
developed to address this gap with improvement of the barrier function of LES and
reversible design if necessary.
PMID- 23155538
TI - Does the insanity defence lead to an abuse of human rights?
PMID- 23155539
TI - Strengthening mental health systems.
PMID- 23155540
TI - The prostitution of psychiatry: some are shameless, others are just easy.
PMID- 23155541
TI - A survey of the appreciation of anaerobic infections by Venezuelan medical
students.
AB - The background of a successful clinical diagnosis of an anaerobic infection is
dependent, to a large extent, on the skills, knowledge and awareness that the
examining clinician acquired during his or her time as a medical student. To
assess the quality of current teaching protocols in anaerobic microbiology in
Venezuela, a survey was carried out among 300 medical students attending three
medical schools. The survey consisted of a questionnaire of 18 questions on
fundamental aspects of anaerobic bacteria,the infections they cause and their
treatment. Although there was only a poor response rate (from 16% of students),
the conclusion of the study was that there was a distinct lack of knowledge and
appreciation of anaerobic infections among medical students in Venezuela.
PMID- 23155542
TI - 24 hour availability of echocardiography in Acute Medicine: time to get out of
our 'silos'.
PMID- 23155543
TI - [Abstracts of the 6th Croatian Congress of Nephrology, Dialysis and
Transplantation with International Participation, October 7-10, 2011, Croatia].
PMID- 23155544
TI - [Abstracts of the 5th Symposium of the Croatian Nurses Association, Society for
Nephrology, Dialysis and Renal Transplantation, October 7-10, 2011, Croatia].
PMID- 23155545
TI - Menstrual regulation, unsafe abortion, and maternal health in Bangladesh.
AB - Maternal mortality has declined considerably in Bangladesh over the past few
decades. Some of that decline--though precisely how much cannot be quantified--is
likely attributable to the country's menstrual regulation program,which allows
women to establish nonpregnancy safely after a missed period and thus avoid
recourse to unsafe abortion. Key Points. (1) Unsafe clandestine abortion persists
in Bangladesh. In 2010, some 231,000 led to complications that were treated at
health facilities, but another 341,000 cases were not. In all, 572,000 unsafe
procedures led to complications that year. (2) Recourse to unsafe abortion can be
avoided by use of the safe, government sanctioned service of menstrual regulation
(MR)--establishing nonpregnancy after a missed period, most often using manual
vacuum aspiration. In 2010, an estimated 653,000 women obtained MRs, a rate of 18
per 1,000 women of reproductive age. (3) The rate at which MRs result in
complications that are treated in facilities is one-third that of the
complications of induced abortions--120 per 1,000 MRs vs. 357 per 1,000 induced
abortions. (4) There is room for improvement in MR service provision, however. In
2010, 43% of the facilities that could potentially offer it did not. Moreover,
one-third of rural primary health care facilities did not provide the service.
These are staffed by Family Welfare Visitors, recognized to be the backbone of
the MR program. In addition, one-quarter of all MR clients were denied the
procedure. (5) To assure that trends toward lower abortion-related morbidity and
mortality continue, women need expanded access to the means of averting unsafe
abortion. To that end, the government needs to address barriers to widespread,
safe MR services, including women's limited knowledge of their availability, the
reasons why facilities do not provide MRs or reject women who seek one, and the
often poor quality of care.
PMID- 23155546
TI - [Proceedings of the 15th Symposium of Intensive Medicine, June 27-29, 2009,
Brijuni, Croatia].
PMID- 23155547
TI - A long and winding road: federally qualified health centers, community variation
and prospects under reform.
AB - Community health centers have evolved from fringe providers to mainstays of many
local health care systems. Those designated as federally qualified health centers
(FQHCs), in particular, have largely established themselves as key providers of
comprehensive, efficient, high-quality primary care services to low-income
people, especially Medicaid and uninsured patients. The Center for Studying
Health System Change's (HSC's) site visits to 12 nationally representative
metropolitan communities since 1996 document substantial growth in FQHC capacity,
based on growing numbers of Medicaid enrollees and uninsured people, increased
federal support, and improved managerial acumen. At the same time, FQHC
development has varied considerably across communities because of several
important factors, including local health system characteristics and financial
and political support at federal, state and local levels. Some communities-
Boston; Syracuse, N.Y.; Miami; and Seattle--have relatively extensive FQHC
capacity for their Medicaid and uninsured populations, while other communities-
Lansing, Mich.; northern New Jersey; Indianapolis; and Greenville, S.C.--fall in
the middle. FQHC growth in Phoenix; Little Rock, Ark.; Cleveland; and Orange
County, Calif.; has lagged in comparison. Today, FQHCs seem poised to play a key
role in federal health care reform, including coverage expansions and the
emphasis on primary care and medical homes.
PMID- 23155548
TI - [Proceedings of 6th Croatian Congress on Emergency Medicine with international
participation, November 19-20, 2009, Zagreb, Croatia].
PMID- 23155549
TI - Limited options to manage specialty drug spending.
AB - Spending on specialty drugs--typically high-cost biologic medications to treat
complex medical conditions--is growing at a high rate and represents an
increasing share of U.S. pharmaceutical spending and overall health spending.
Absence of generic substitutes, or even brand-name therapeutic equivalents in
many cases, gives drug manufacturers near-monopoly pricing power and makes
conventional tools of benefit design and utilization management less effective,
according to a new qualitative study from the Center for Studying Health System
Change (HSC). Despite the dearth of substitutes, cost pressures have prompted
some employers to increase patient cost sharing for specialty drugs. Some believe
this is counter-productive, since it can expose patients to large financial
obligations and may reduce patient adherence, which in turn may lead to higher
costs. Utilization management has focused on prior authorization and quantity
limits, rather than step-therapy approaches--where lower-cost options must first
be tried--that are prevalent with conventional drugs. Unlike conventional drugs,
a substantial share of specialty drugs--typically clinician-administered drugs-
are covered under the medical benefit rather than the pharmacy benefit. The
challenges of such coverage--high drug mark-ups by physicians, less utilization
data, less control for health plans and employers--have led to attempts to
integrate medical and pharmacy benefits, but such efforts are still in early
development. Health plans are experimenting with a range of innovations to
control spending, but the most meaningful, wide-ranging innovations may not be
feasible until substitutes, such as biosimilars, become widely available, which
for many specialty drugs will not occur for many years.
PMID- 23155550
TI - Emergency preparedness and community coalitions: opportunities and challenges.
AB - Being prepared for a natural disaster, infectious disease outbreak or other
emergency where many injured or ill people need medical care while maintaining
ongoing operations is a significant challenge for local health systems. Emergency
preparedness requires coordination of diverse entities at the local, regional and
national levels. Given the diversity of stakeholders, fragmentation of local
health care systems and limited resources, developing and sustaining broad
community coalitions focused on emergency preparedness is difficult. While some
stakeholders, such as hospitals and local emergency medical services,
consistently work together, other important groups--for example, primary care
clinicians and nursing homes--typically do not participate in emergency
preparedness coalitions, according to a new qualitative study of 10 U.S.
communities by the Center for Studying Health System Change (HSC). Challenges to
developing and sustaining community coalitions may reflect the structure of
preparedness activities, which are typically administered by designated staff in
hospitals or large medical practices. There are two general approaches policy
makers could consider to broaden participation in emergency-preparedness
coalitions: providing incentives for more stakeholders to join existing
coalitions or building preparedness into activities providers already are
pursuing. Moreover, rather than defining and measuring processes associated with
collaboration--such as coalition membership or development of certain planning
documents--policy makers might consider defining the outcomes expected of a
successful collaboration in the event of a disaster, without regard to the
specific form that collaboration takes.
PMID- 23155551
TI - Medicare and Medicaid programs: Hospital Outpatient Prospective Payment and
Ambulatory Surgical Center Payment Systems and Quality Reporting Programs;
electronic reporting pilot; Inpatient Rehabilitation Facilities Quality Reporting
Program; revision to Quality Improvement Organization regulations. Final rule
with comment period.
AB - This final rule with comment period revises the Medicare hospital outpatient
prospective payment system (OPPS) and the Medicare ambulatory surgical center
(ASC) payment system for CY 2013 to implement applicable statutory requirements
and changes arising from our continuing experience with these systems. In this
final rule with comment period, we describe the changes to the amounts and
factors used to determine the payment rates for Medicare services paid under the
OPPS and those paid under the ASC payment system. In addition, this final rule
with comment period updates and refines the requirements for the Hospital
Outpatient Quality Reporting (OQR) Program, the ASC Quality Reporting (ASCQR)
Program, and the Inpatient Rehabilitation Facility (IRF) Quality Reporting
Program. We are continuing the electronic reporting pilot for the Electronic
Health Record (EHR) Incentive Program, and revising the various regulations
governing Quality Improvement Organizations (QIOs), including the secure
transmittal of electronic medical information, beneficiary complaint resolution
and notification processes, and technical changes. The technical changes to the
QIO regulations reflect CMS' commitment to the general principles of the
President's Executive Order on Regulatory Reform, Executive Order 13563 (January
18, 2011).
PMID- 23155552
TI - Medicare program; revisions to payment policies under the physician fee schedule,
DME face-to-face encounters, elimination of the requirement for termination of
non-random prepayment complex medical review and other revisions to Part B for CY
2013. Final rule with comment period.
AB - This major final rule with comment period addresses changes to the physician fee
schedule, payments for Part B drugs, and other Medicare Part B payment policies
to ensure that our payment systems are updated to reflect changes in medical
practice and the relative value of services. It also implements provisions of the
Affordable Care Act by establishing a face-to-face encounter as a condition of
payment for certain durable medical equipment (DME) items. In addition, it
implements statutory changes regarding the termination of non-random prepayment
review. This final rule with comment period also includes a discussion in the
Supplementary Information regarding various programs . (See the Table of Contents
for a listing of the specific issues addressed in this final rule with comment
period.)
PMID- 23155553
TI - Regulation. Is scrutiny of care poorer the further you are from London?
PMID- 23155554
TI - Equality. The unplanned racist impact of reform.
PMID- 23155555
TI - Trust chiefs fear regulators would not spot scandal.
PMID- 23155557
TI - Easton: we must tackle cost-cutting masked as efficiency.
PMID- 23155556
TI - Data quality concerns delay mental health tariff.
PMID- 23155558
TI - CCG budgets face complications, says DH.
PMID- 23155559
TI - The argument over NHS competition isn't settled yet.
PMID- 23155560
TI - Darzi and Howitt international healthcare. NHS must grasp a world of opportunity.
PMID- 23155561
TI - Beyond inspections.
PMID- 23155562
TI - Playing fair on treatments.
PMID- 23155563
TI - Public health. Change of heart.
PMID- 23155564
TI - Medicines management. Put it in the recycling bin.
PMID- 23155565
TI - Service improvement. Falling through the cracks.
PMID- 23155566
TI - Innovation switched on.
PMID- 23155567
TI - Innovation: case studies. Trials in the real world.
PMID- 23155568
TI - Commissioning. Now for the hard bit.
PMID- 23155569
TI - Guidance. Tackling the 'mindset problem'.
PMID- 23155570
TI - Case study. Risk and reward.
PMID- 23155571
TI - Infertility. How to avoid stretch marks on your budget.
PMID- 23155572
TI - Clinical leaders. The move from medic to manager.
PMID- 23155573
TI - Patient safety. The way ahead for whistleblowing.
PMID- 23155574
TI - Performance. Getting the most out of out of area.
PMID- 23155575
TI - Integrative review of nursing research: scientific rigor required.
PMID- 23155576
TI - [Nursing care for patients undergoing pharmacological stress echocardiography:
implications for clinical practice].
AB - The study aim was both to identify signs and symptoms previous to and during the
pharmacological stress echocardiography test and to describe the nurse's role and
nursing care principles for this exam. This is a descriptive study, carried out
in cardiac care unit in a University Hospital in Porto Alegre, RS. Two hundred
forty-six records of patients submitted to stress echocardiography were
retrospectively reviewed, according to four different pharmacological schedules.
The statistical comparison showed that signs and symptoms were related to the
type of drug used during the exam, namely: typical angina, precordial ache,
tiredness, headache and premature complexes. These results enabled a better
understanding of pharmacological stress echocardiography and the
instrumentalization of nurses in order to plan individualized and qualified
nursing care assistance. Aside from helping develop nursing practices for the
pharmacological stress echocardiography test this knowledge could also be used by
nurses who carry out their activities in institutions that use this diagnostic
method.
PMID- 23155577
TI - [Educational activities for people with chronic disease: grants for nursing].
AB - This is an intervention study conducted in a Unidade Basica de Saude (Basic
Health Unit) in Colombo, Parana, Brazil from March to November 2009, with 35
carriers of chronic diseases aged between 18 and 60 years, and enrolled in the
Hypertension and Diabetes Program. The objectives were to identify their
knowledge about arterial hypertension and act through educational group
activities. Data were collected though semistructured interviews and four group
meetings, and the following categories emerged from the analysis: "Understanding
of the disease" and "Ways of caring". It was found that users knew the disease,
its risk factors and possible complications, and that educational activities
favored the sharing of experiences,provided reflection and the possibility of
treatment management. This is a strategy that should be used and promoted by
nurses.
PMID- 23155578
TI - [Assessment of quality of nursing prescriptions in public teaching hospital].
AB - A multicenter, cross-sectional study took place from December 2009 to June 2010
and aimed to assess the quality of Nursing Prescription (NP) in two public
teaching hospitals. The sample consisted of 1,307 NP and data were processed
using the G-test and chi-square. The determination of the quality of NP was based
on the classification indices reported in literature. Among the results, 1,083
(82.8%) correct and appropriate NP, 154 (11.8%) inadequate NP and 52 (3.9%)
incomplete NP were found. In 18 (1.37%) patient charts, the NP was nonexistent.
There was statistic signficance (alpha < 0.05) for incomplete and absent NP
between the two hospitals (0.00), as well as inappropriate NP between age groups
(0.03). It was concluded that, in the hospitals under study, the NP needs to be
improved both in terms of quantity and quality.
PMID- 23155579
TI - [Nurse's assessment of oral health of elderly people: OHAT validity and
reliability].
AB - The aim of the study was to apply the Oral Health Assessment Tool (OHAT)for
determination of the reliability and validity indexes, when utilized by nursing
staff The OHAT was administered to 50 elderly individuals. The exams were
performed in different periods of times by a Nurse and a Dental Surgeon (DS). The
determination of internal consistency was verified through Cronbach's Alpha
Coeficient and ANOVA. For the determination of stability and reliability, the
percentage agreement and Kappa test were considered. There was no statistical
difference among the final averages obtained by the DS and the nurse (p=0.41).
There was a higher internal consistency in the exams performed by the DS. The
Kappa value of the instrument reached 0.46, being considered moderate. The OHAT
instrument can be used by nurses as a screening tool however, previous training
is needed for criteria standardization.
PMID- 23155580
TI - [Characteristics of victims and fatal accidents at the workplace].
AB - This is a quantitative, descriptive, retrospective documental study on fatal
accidents occurred during the period from o2006 to 2010, in which workers were
treated at Hospital do Trabalhador, located in Curitiba/Parand. We selected 25
notifications for the outcome death. This study aimed to characterize victims and
fatal occupational accidents. Fatal occupational accidents hit workers with a
mean age of 35 years (SD = 13.0694), of the male sex, n = 23 (92%). Typical
occupational accidents accounted for 52% (n = 13) of cases. One of the preventive
measures proposed to reduce the number of fatal occupational accidents is the
performance of educational and preventive work at the workplace by nurses.
Moreover, it is necessary to rethink transit violence as a relevant factor for
the cause of death of workers as well.
PMID- 23155581
TI - [Classification of patients in a traumatology unit].
AB - Study with the aim to classify patients in accordance with the degree of
dependence on nursing care, estimate the size of the nursing staff and correlate
instruments. Perroca and Fugulin's instruments were used to classify patients
admitted for a period of 30 days and to estimate the size of the nursing staff
the formula recommended by the Federal Nursing Board COFEN No. 293/0 was used.
Included were 157 patients, 42.0% were classified as dependent on intermediate
care, and for 50.3% of patients, the degree of dependence zas classified as
minimum care. Regarding the size of the nursing staff the existing staff in the
surveyed unit consisted of 20 employees, while the necessary size should be 32
employees, divided in thefour shifts. The instruments showed a strong correlation
(rp=0.88). It is believed that the classification of patients in order to
estimate the size of the nursing team can provide more quality to care.
PMID- 23155582
TI - [Heavy alcohol consumption among women].
AB - This descriptive, exploratory study aimed to characterize women attending a
Teaching Hospital in Northwest Parana, for alcohol abuse in the years 1999 to
200, according to sociodemographic data of intoxication and associated with
trauma and violence. Among 823 visits, the most frequent age range was from 20 to
49 years (58.32%). 13 (1.58%) were pregnant, 12.5% had 9-12 years of schooling.
Liquor was the main beverage used and its intake was more prevalent at night.
Approximately 156 (18.96%) women required hospitalization. Hospital avoidance was
observed in 8.5% of cases. We conclude that woman are likely to abuse alcohol,
and this study enabled a description of the areas in women's health that are
impacted allowing the implementation of preventive measures to decrease
occurrence and recurrence in this population.
PMID- 23155583
TI - [Educational strategy addressed to nurses in primary care for infertility: an
intervention study].
AB - The objective was to assess the impact of an educational strategy approaching
infertility assistance; and verify practices introduced into the daily work of
the participants after this intervention. Research-action developed with 11
nurses from the Family Health Strategy, in Fortaleza-CE, through the reading of a
brochure in a "circle of conversation." Data were collected in August and October
2010, before, immediately after and 60 days after the intervention. An increase
in the levels of knowledge was noted immediately after the intervention, when all
participants had a "more than good" or "very good" level of knowledge, leaving
behind the "little" and "good" levels rated before the intervention; at 60 days,
a "good" level of knowledge was noted again, showing a relative decrease in
knowledge. There was self-recognition of the ability to introduce practices into
the daily work after the intervention, confirming the positive impact thereof
PMID- 23155584
TI - [Occupational stress: evaluation of intensive care nurses who work at nighttime].
AB - Descriptive, cross-sectional study, which aimed to evaluate the stress level of
nighttime intensive care nurses. The Bianchi Stress Scale was applied to 26
(100%) nurses from five hospitals. In data analysis, the Pearson Chi-square test
was used and it was noticed that the stress among nurses in a public (3.36
points) and private facility (3.02 points) was classified at the median level and
there was no statistical significance (p = 0.90) forr stress, according to the
type of institution. Variables that most contributed to the occurrence of stress
were: working conditions (nighttime work closed and critical unit), patient
severity, management activities associated with care. It was concluded that the
workplace was positively associated with the stress in nurses working at
nighttime and that its onset and effects can be minimized through improvements in
the structure and organization of the place where the healthcare providers work.
PMID- 23155585
TI - [Maternal risk factors for premature births in a public maternity hospital in
Imperatriz-MA].
AB - Despite advances in obstetrics, prematurity is still a major public health
problem because of the neonatal morbidity and mortality it causes. The objective
of this study was to investigate maternal risk factorsfor premature births in a
public maternity in the city of Imperatriz-MA. A cross-sectional comparative
study was conducted with 116 mothers, through structured interviews. The data
were analyzed using Epi-Info version 3.5.1. The variables that showed
statistically significant association with preterm delivery were monthly income
below two minimum wages (p = 0.046), stress during pregnancy (p = 0.027),
primiparity (p = 0.044), absent or inadequate prenatal care (p <0.001) and
clinical complications in pregnancy (p<0.001). The results show that the maternal
risk factors implicated in prematurity are related mainly with lifestyle,
socioeconomic and clinical variables, and prenatal care.
PMID- 23155586
TI - [Educational geronto-technology for ostomized seniors from a complexity
perspective].
AB - We aimed to present the educational booklet as a geronto-technological product
for caring for ostomized seniors from a complexity perspective. This was
accomplished in the second semester of 2007 in a hospital in the south of Brazil.
The data were collected through interviews and presented in the form of an
educational booklet. The booklet was validated by ostomized seniors and by a
nurse who had been working with these elderly patients. The booklet was presented
as a geronto-technology able to help ostomized seniors and their families
understand the rights of ostomized people; concepts and types of stomas; care of
ostomy; and the importance of the family and the support group for care. In
conclusion, the educational booklet is presented as a health promotion tool which
makes the health educative process easier.
PMID- 23155587
TI - [Support group as a strategy of care: the importance for relatives of drug
users].
AB - The objective was to investigate the perception by relatives of drug users about
the importance of the support group as a strategy of care. We conducted a
descriptive study with qualitative approach, in the second half of 2010, in a
psychosocial care center for users of alcohol and other drugs (CAPS AD), in a
city in the extreme south of Brazil with ten relatives. Data were collected by
semistructured interviews and analyzed by thematic analysis. It was found that
the group is an alternative to hospitalization in a psychiatric hospital, can
provide access and regular monitoring by health professionals, helps understand
what addiction is, provides tools for care and allows for the social
rehabilitation of the addict. The support group was concluded to be an important
strategy for caring for relatives of drug users, presenting itself as a
technology to be incorporated by nurses in their daily practice.
PMID- 23155588
TI - [Men and women living in marital violence: socioeconomic aspects].
AB - Quantitative and descriptive study aiming to identify socioeconomic
characteristics of men and women with a history of domestic violence. We
conducted interviews with 50 men and 50 women. Nearly all subjects were self
declared black. Most did not have too many years of school education. Men perform
occupations that are public and women do predominantly domestic activities. Only
3 women (6%) are considered financially independent. The degree of economic
dependence is directly related to the level of education that has been
established as a prerequisite to enter into the labor market. The situation is
even more precarious for women interviewed with fewer years of education and a
high degree of financial dependence that interferes with their empowerment to
address domestic violence. Health professionals, especially nurses, should
address the social inequities and improve the socioeconomic context of users to
identify situations that endanger the health of the population.
PMID- 23155589
TI - [Identification of the nursing diagnosis of fall risk in elderly with stroke].
AB - The purpose of this study was to verify the presence of a nursing diagnosis of
fall risk in elderly with stroke. Observational exploratory and cross-sectional
study with descrziptive analysis. Performed in a charitable rehabilitation
association in Fortaleza city, from January to March 2010, by primary source, by
interviews and physical examination with elderly people who had at least one
episode of stroke 37 individuals participated of which 20 (54.1%) were women,
with mean age of 70.6years, and 18 (48.6%) lived with a partner and had an
average of 5.2 years of study. The risk of falls was found in all elderly. Among
the risk factors identified it is possible to highlight Impaired balance (100%),
Age above 65 years (83.7%), and Proprioceptive deficit (83.7%). Nurses must
consider the risk of falls as a nursing carefocus and implement and evaluate the
results of interventions for fall prevention.
PMID- 23155590
TI - [Instrument to collect data for critical patients based on the theory of basic
human needs].
AB - This is an exploratory study based on qualitative approach that aimed to
collectively construct an instrument to collect data for patients in the
Intensive Care Unit (ICU), based on the Theory of Basic Human Needs (NHB). Data
collection was through a focus group with four nurses from the ICU and four
residents from the Nursing-Health Integrated Residency (RIS) program in seven
meetings in 2009. The discussions produced in each session were analyzed as
recommended by Horta. The instrument was divided into seven groups and 17
subgroups of needs. After testing and suggestions from participants, we
elaborated the final version of the instrument and a guidance manualfor
completing it, according to the need expressed by the group. Validation of the
instrument and the manual and inclusion of teaching of the nursing process in the
RIS activity program are suggested.
PMID- 23155591
TI - [Option and evasion of a bachelor's degree programme in nursing evaded students'
perception].
AB - Qualitative study, developed in a Federal University in southern Brazil aiming to
know the motives for choosing and evading a Bachelor's degree programme in
Nursing, in the evaded students 'perception. The data were collected through a
questionnaire sent by e-mail to 19 evaded students. The 9 questionnaires that
returned were submitted to Qualitative Textual Analysis, and two categories
emerged motives to opt for the nursing programme and motives to evade from the
nursing programme. The results showed that the option for the programme is
associated to personal vocation, perception of Nursing as a profession of care,
and its closeness to the health area. Evasion seems to be related to passing the
first option of undergraduate programme, ignorance about the profession,
financial difficulties, and professional depreciation. We demonstrated that
greater emphasis should be put on promoting knowledge about the nursing work,
areas of activity and attributions.
PMID- 23155592
TI - [Patients living with HIV/AIDS and co-infection by tuberculosis: difficulties
associated with treatment compliance or dropout].
AB - Research carried out in Fortaleza-CE, between March and April 2011, with the
objective of describing the difficulties that influence non-compliance to
tuberculosis treatment or treatment dropout in patients infected with Human
Immunodeficiency Virus. Qualitative study with data collected through a semi
structured interview, applied to patients with acquired immunodeficiency syndrome
and with co-infection of tuberculosis. The Collective Subject's Speech was used
for result analysis. Patients reported difficulties related to socioeconomic
aspects, lifestyle and drug use. The consumption of alcohol and illicit drugs
were factors that led to the discontinuance of the therapeutic process of the
disease. We conclude that the barriers related to social economical aspects and
to lifestyle are more difficult to be faced for a continuous compliance to
treatment, making the role played by health professionals necessary, supported by
more effective public and social policies.
PMID- 23155593
TI - [Users' perceptions of urgency and reasons for using the mobile pre-hospital care
service].
AB - The Mobile Emergency Care Services handle urgent situations of various types, and
demand for this service occurs according to the perception of the user regarding
what is urgent. The aim of the study was to analyze the perceptions of urgency by
users who demand care from a Mobile Emergency Care Service in Porto Alegre and to
identify the reasons for these requests. In this explomratory-descriptive study,
with qualitative approach, data were collected through semi-structured interviews
conducted by telephone, during theperiod from February to April 2009. Thematic
analysis was used to analyze the information. Users consider urgent life
threatening conditions, which require a quick response, and visible situations,
such as bleeding, chronic diseases, and difficulties in transportation. Users
themselves feel motivated to call the service due to it being rapid and free, and
for transportation. The perceptions of users regarding urgency were diverse,
sometimes consistent with the biomedical perspective of health providers and
sometimes with their own social context.
PMID- 23155594
TI - [Pleasure in nursing technicians working at an emergency unit of a public
university hospital].
AB - This study aimed to reveal the main aspects of the work process and feelings of
pleasure experienced by nursing technicians who work at an emergency unit in
Parana, Brazil. The theoretical basis is the psychodynamics of work. This is a
qualitative and descriptive study. Data were collected and analyzed using a semi
structured interview and the content analysis technique. Subjects were selected
using a snowball sampling. Important aspects of the work process were revealed
such as the unpredictability of working in an emergency unit, the impact of team
work, and the comprehensive care model as a precursor to humanized care. Pleasure
originates from the acknowledgement of their work either by the working subject
him/herself by patients or society; and from the team work, realized by the
cooperation among professionals. Feelings of pleasure are linked to the
acknowledgment of their work, which should be valued since gratification
contributes to the psychological health of workers.
PMID- 23155595
TI - [Assessment of body weight changes in patients on peritoneal dialysis].
AB - This study had as its main objective to assess the variation in body weight of
patients on peritoneal dialysis (DP) during the first year of treatment and as a
secondary goal to identify patients with criteria for metabolic syndrome (SM).
Observational study conducted with 35 patients of a university hospital. Data
were collected on the clinical and demographic status, change of body weight and
criteria for SM from the sample. After 12 months of initiation of dialysis,
approximately 40% of patients showed overweight and/or obesity. The average
variation of body weight after one year was 3.7 Kg, and the largest variation was
found in the first three months, with values of 2.2 Kg The prevalence of SM was
30%. It was concluded that the most important change of body weight happened in
the first year of treatment and there is a high prevalence of SM in patients on
DP.
PMID- 23155596
TI - [Occupational violence experienced by nursing staff in hospital emergency
service].
AB - This research objectives were: to discover the sociodemographic profile of the
nursing staff that works in the hospital emergency service, identify the main
types of occupational violence suffered by this team. Cross-sectional descriptive
study done in a general hospital in Duque de Cazxias/Rio de Janeiro. The data,
collected on August, 2009, was put in tables for subsequent univariate analysis.
The sample of respondents comprised 30 workers. The analyzed data showed that the
majority of employees interviewed were victims of occupational violence (76.7%).
The main causes of occupational violence were the companions (87.0%) followed by
patients (52.2%). The more frequentform of aggression was verbal aggression
(100.0%). The results showed that these workers have little expectation on
changing the current situation and do not believe that their managers can assist
them in the problem.
PMID- 23155597
TI - [Functional capacity in elderly longevity: an integrative review].
AB - This is an integrated literature review intended to get to know the Brazilian
scientific production regarding the functional capacity of the elderly. BDENF,
LILACS, MEDLINE and SciELO databases were consulted in the sampling period from
January, 2001, to September, 2010. Eight articles were selected with nursing
professionals (4) as the main authors of such publications. Publication year of
the articles is between 2006 and 2010, with predomination of quantitative
research focused on the multidimensionality of the elderly. Questionnaires and
scales were used to assess the functional capacity of the elderly and
constraining factors for its performance were also indicated. Scientific studies
on the theme are incipient, which evidences the need for further research aiming
to improve the quality of life of the elderly.
PMID- 23155598
TI - [Patient education on drug treatment regimen in the process of hospital
discharge: an integrative review].
AB - Adequate patient education about drug treatment regimen at discharge contributes
to the continuity of home care. Integrative review aimed to analyze and
synthesize the scientific literature about patient education on medication
regimen in the hospital discharge process. We consulted the databases Medical
Literature Analysis and Retrieval System on-line (MEDLINE) and Latin-American and
Caribbean Center on Health Sciences Information (LILACS), and selected 24
articles published between 2005 and 2010. Inter-related aspects, such as
structured discharge planning, medication reconciliation, drug education, adverse
drug events and medication adherence, permeate the theme.
PMID- 23155599
TI - [Montessori method applied to dementia - literature review].
AB - The Montessori method was initially applied to children, but now it has also been
applied to people with dementia. The purpose of this study is to systematically
review the research on the effectiveness of this method using Medical Literature
Analysis and Retrieval System Online (Medline) with the keywords dementia and
Montessori method. We selected lo studies, in which there were significant
improvements in participation and constructive engagement, and reduction of
negative affects and passive engagement. Nevertheless, systematic reviews about
this non-pharmacological intervention in dementia rate this method as weak in
terms of effectiveness. This apparent discrepancy can be explained because the
Montessori method may have, in fact, a small influence on dimensions such as
behavioral problems, or because there is no research about this method with high
levels of control, such as the presence of several control groups or a double
blind study.
PMID- 23155600
TI - [Risk and vulnerability in the practice of professional healthcare].
AB - The purpose of this study is to analyze the risks and vulnerability found in
professional healthcare and the safe practices adopted based on academic research
in the field of healthcare and nursing, by means of an integrative review. The
articles were found in the LILACS and SCIELO databases,from the years 2005-2010,
in a search for the descriptors vulnerability, risk, and occupational and
personal health risks, establishing a sample of 21 articles. In basic healthcare,
risks and vulnerabilities are related to the lack of resources needed for work,
physical violence and emotional strain. In a hospital context, the problems are
related to accidents with biological materials caused by improper use and failure
to adopt protective measures, as well as excessive work and self-confidence. The
importance of implementing public policies in worker health to improve working
conditions and provide greater satisfaction and professional awareness is
emphasized.
PMID- 23155601
TI - Myths about stroke--on the road to change.
PMID- 23155602
TI - [Prevalence of overweight and obesity in adult rural population of the northern
part of Backa and Banat].
AB - BACKGROUND/AIM: Obesity represents one of the frequent health problems in
developed countries today. It is related to cardiovascular diseases, diabetes and
various cancer forms. The aim of the study was to determine the prevalence of
overweight and obesity in adult population of the northern Badka and Banat.
METHODS: On the basis of a multistage stratified random sampling, 4505
individuals of the age 40.61 +/- 11.29 years took part in the study. The study
included 46 rural settlements. The overweight and obesity prevalence was obtained
using the anthropometric indicators of body mass index (BMI), waist circumference
(WC) and the waist to hip ratio (WHR). The correlations among BMI, WC and WHR
were determined by the Pearson's correlation coefficient while the multiple
regression analysis was used for correlating sociodemographic parameters and the
obesity index. RESULTS: A significant positive correlation was found in relation
to all anthropometric parameters in both sexes. The data indicated that 66.32% of
males and 49.68% of females had an overweight problem. On average, approximately
38.52% of subjects of both sexes were overweight, while 19.48% were obese. The
factors that largely contributed to higher values of the obesity index were the
age of male subjects and the age, education and origin in females. Ragarding the
female subjects, the level of education negatively correlated with the level of
nutritional condition. CONCLUSION: The prevalence values of the overweight and
obese subjects, obtained on the basis of the anthropometric parameters, vary.
However, regardless methods applied, the percentage of the overweight and obese
persons is very high, being among the highest recorded in European populations.
The obtained results indicate the necessity of introducing better education
programmes and conducting regular health controls among citizens in these
regions.
PMID- 23155603
TI - Prevalence of renal dysfunction and its influence on functional capacity in
elderly patients with stable chronic heart failure.
AB - BACKGROUND/AIM: Chronic heart failure (CHF) is highly prevalent and constitutes
an important public health problem around the world. In spite of a large number
of pharmacological agents that successfully decrease mortality in CHF, the
effects on exercise tolerance and quality of life are modest. Renal dysfunction
is extremely common in patients with CHF and it is strongly related not only to
increased mortality and morbidity but to a significant decrease in exercise
tolerance, as well. The aim of our study was to investigate the prevalence and
influence of the renal dysfunction on functional capacity in the elderly CHF
patients. METHODS: We included 127 patients aged over 65 years in a stable phase
of CHF. The diagnosis of heart failure was based on the latest diagnostic
principles of the European Society of Cardiology. The estimated glomerular
filtration rate (eGRF) was determined by the abbreviated modification of diet in
renal disease (MDRD2) formula, and patients were categorized using the kidney
disease outcomes quality initiative (K/DOQI) classification system. Functional
capacity was determined by the 6 minute walking test (6MWT). RESULTS: Among 127
patients, 90 were men. The average age was 72.5 +/- 4.99 years and left
ventricular ejection fraction (LVEF) was 40.22 +/- 9.89%. The average duration of
CHF was 3.79 +/- 4.84 years. Ninty three (73.2%) patients were in New York Heart
Association (NYHA) class II and 34 (26.8%) in NYHA class III. Normal renal
function (eGFR > or = 90 mL/min) had 8.9% of participants, 57.8% had eGFR between
60-89 mL/min (stage 2 or mild reduction in GFR according to K/DOQI
classification), 32.2% had eGFR between 30-59 mL/min (stage 3 or moderate
reduction in GFR) and 1.1% had eGFR between 15-29 mL/min (stage 4 or severe
reduction in GFR). We found statistically significant correlation between eGFR
and 6 minute walking distance (6MWD) (r = 0.390, p < 0.001), LVEF (r = 0.268, p <
0.05), NYHA class (p = -0.269, p < 0.05) and age (r = 0.214, p < 0.05). In
multiple regression analysis only patients' age was a predictor of decreased 6MWD
< 300 m (OR = 0.8736, CI = 0.7804 - 0.9781, p < 0.05). CONCLUSION: Renal
dysfunction is highly prevalent in the elderly CHF patients. It is associated
with decreased functional capacity and therefore with poor prognosis. This study
corroborates the use of eGFR not only as a powerful predictor of mortality in
CHF, but also as an indicator of the functional capacity of cardiopulmonary
system. However, clinicians underestimate a serial measurement of eGFR while it
should be the part of a routine evaluation performed in every patient with CHF,
particularly in the elderly population.
PMID- 23155604
TI - [Reading characteristics of deaf and hard-of-hearing pupils].
AB - BACKGROUND/AIM: Speech motor mechanisms play a crucial role in the process of
demutization, due to the fact that they cover all the elements of the successive
development of spech production movements leading to speech formation (so-called
kinesthesia in speach). The aim of this study was to estimate the impact of
perceptual motor actions on the cognitive process of reading in 130 students in
regular schools and schools for the deaf and hard-of-hearing children in the
Republic of Serbia. METHODS: Kostic and Vladisavljevic test consisted of the ten
levels weight was used for the assessment of reading speed. To assess
understanding of text read by verbal responses, we used three-dimensional adapted
reading test of Helene Sax. RESULTS: The triage-articulation test for assessing
reading speed (Kostie and Vladisavljevic's test according to the weight of ten
levels, revealed that students in regular schools statistically significantly
faster read texts as compared to the deaf students. The results of the three
dimensional adapted reading test of Helena Sax, show that the words learned by
deaf children exist in isolation in their mind, i.e., if there is no standard of
acoustic performance for graphic image, in deaf child every word, printed or
written, is just the sum of letters without meaning. CONCLUSION: There is a
significant difference in text reading speed and its understanding among the
children who hear and the deaf and hard-of-hearing children. It is essential that
in deaf and heard-of-hearing children education, apart from the development of
speech, parallelly use the concept of semantic processing in order to get each
word by the fullness of its content and the possibility of expanding its meaning
in a variety of assets.
PMID- 23155605
TI - [Photorefractive keratectomy for correction of myopia--our one-year experience].
AB - BACKGROUND/AIM: Photorefractive keratectomy (PRK), after laser in situ
keratomileusis (LASIK), is commonly performed refractive surgical method
worldwide. The aim of this study was to examine the effectiveness and safety of
PRK in correction of various strengths of myopia and to assess how much corneal
tissue is being removed with one diopter sphere (Dsph) correction by using
different optical zones (OZ). METHODS: A prospective study with a follow-up
period of 6 months included 55 patients of which 100 myopic eyes were treated by
PRIK method (one eye was included in 10 patients). Myopic eyes with a
preoperative best corrected visual acuity (BCVA) = 1.0 (20/20) were analysed. In
order to assess the effectiveness of PRK operated myopic eyes were divided into
four groups according to the dioptric power: (1) < or = -1.75 Dsph (n=26); 2)
from -2 to -3.75 Dsph (n=44); 3) from -4 to -6.75 Dsph (n=23), and 4) > or = -7
Dsph (n=7). Myopic eyes with preoperative BCVA < or = 0.9 (amblyopic eyes) were
excluded from the study, as well as eyes with astigmatism > -1.5 Dcyl. To assess
the effectiveness of PRK we examined the percentage of eyes in the mentioned
groups, which derived uncorrected visual acuity (UCVA) 6 months after the
intervention to the following: (a) UCVA = 1.0 (20/20) and (b) UCVA > or = 0.5
(20/40). To assess the safety of PRK we examined the frequency of intraoperative
and postoperative complications. To estimate how much corneal tissue was removed
with one Dsph correction by using different OZ, we used preoperative and
postoperative (after 6 months) central pachymetry values expressed in microm and
volume of cornea (central 7 mm) expressed in mm3. In that sense, we used only the
myopic eyes with clear preoperative spherical refraction. The total number of
these eyes was 27, of which 16 eyes were treated using a 6.5 mm OZ and 11 eyes
using a 7 mm OZ. RESULTS: Refractive spherical equivalent (RSE) for all eyes was
in the range from -0.75 to -8.75 Dsph, and preoperative mean value of RSE with
standard deviation (mean RSE +/- SD) was -3.32 +/- 1.83 Dsph. Six months after
PRK, 91% of eyes had UCVA = 20/20, and 99% of eyes had UCVA > or = 20/40. In the
first group (< or = -1.75 Dsph) preoperative mean RSE +/- SD was -1.34 +/- 0.32
Dsph, six months after PRK, 96% of eyes had UCVA = 20/20, and 100% of eyes had
UCVA > or = 20/40. In the second group (from -2 to -3.75 Dsph) preoperative mean
RSE +/- SD was - 2.95 +/- 0.57 Dsph, six months after PRK, 89% of eyes had UCVA =
20/20, and 100% of eyes had UCVA > or = 20/40. In the third group (from -4 to
6.75 Dsph) preoperative mean RSE +/- SD was -4.93 +/- 0.70 Dsph, six months after
PRK, 100% of eyes had UCVA = 20/20. In the fourth group (> or = -7 Dsph)
preoperative mean RSE +/- SD was -7.71 +/- 0.67 Dsph, six months after PRK, 57%
of eyes had UCVA = 20/20, and 86% of eyes had UCVA > or = 20/40. There were no
intraoperative complications while postoperative complications occurred in 2
patients - in both cases in one eye (2%). In that cases, epithelial defects were
detected. In the group of eyes that were treated by 6.5 mm OZ mean RSE +/- SD was
-2.45 +/- 0.99 Dsph, the ablation depth per 1 Dsph was 17.54 +/- 5.58 microm and
ablated volume of central 7 mm cornea by 1 Dsph was 0.43 +/- 0.18 mm3. In the
group of eyes that were treated by 7 mm OZ mean RSE +/- SD was -3.32 +/- 2.26
Dsph, the ablation depth per 1 Dsph was 23.73 +/- 6.91 microm and ablated volume
of central 7 mm cornea by 1 Dsph was 0.61 +/- 0.31 mm3. CONCLUSION: PRK is
effective and safe refractive surgical method for correcting myopia up to -8.75
Dsph. OZ size is the main factor determining the depth of the excimer laser
ablation of the corneal tissue volume consumed by 1 Dsph. Higher OZ value
determines higher consumption of cornea tissue.
PMID- 23155606
TI - [The quality of life in patients with diabetes mellitus type 2].
AB - BACKGROUND/AIM: Through its vrious activities, World Health Organization (WHO)
contributed to increasing the understanding of the concept of quality of life.
People with diabetes have a lower quality of life than people without chronic
illnesses. The aim of this study was to examine the differences in the quality of
life, related to health, in patients with diabetes mellitus (DM) type 2 by age,
gender and type of therapy. METHODS: We performed a cross-sectional study at the
outpatient department of the Clinical Center in Novi Sad and the Health Center
Ruma-General Practice. The group consisted of 90 patients with DM type 2, 41 men
and 49 women. The age of respondents was from 40 to 80 years and they were
classifed into four groups according to the ten-year age intervals. We applied
WHO Quality of life questinnaire--BREF 100 composed of four domains: physical
health, psychological health, social relationships and environment. The general
questionnaire asks questions about socio-demographic data, duration of diabetes,
the last value of blood glucose and glycosylated hemoglobin, training for self
control and its implementation, informing patients about their disease, therapy
and its impact on daily activities and the presence of comorbidity. In
statistical analysis the following tests were used: Student's t-test, F-test,
ANOVA (one way). RESULTS: The average duration of DM type 2 was 11.2 +/- 9.2
years. Most of the patients (76%) were trained to self-control and 91% received
enough information about their disease. Oral hypoglycemic preparations were used
by 49%, insulin by 21%, and oral drugs and insulin by 29% patients while 1% were
on a special regime of a diet therapy. Daily activities were performed without
difficulties by over 29%, with some difficulties by 41% and 30% of patients who
could not perform daily activities. The patients with DM type 2 had significantly
lower scors in all 4 domains of quality of life (physical health, psychological
health, social relations, environment). The biggest influence was on physical
domains (51.31). Education level had an imact on physical and psychological
domains. Comorbidity was found in 83% of the respondents. The most common were:
arterial hypertension (63%), chronic cardiovascular disease (46%), neuropathy
(23%), impaired vision 24%, elevated blood lipids (39%) and amputation of toes or
feet (2.2%). The average value HbA1c in the group with comorbidity was 8.47% and
in the group without comorbidity 6.46%. The subjects with comorbidity had low
quality of life assessment in relation to the group without comorbidity: the
domain of physical health (45.64 vs. 79.66), psychological health (50.3 vs.
76.86), social relations (52.97 vs. 75.46) and environment (52.7 vs. 75.06).
CONCLUSION: Diabetes mellitus type 2 has negative influence on the quality of
life. It contributes to the presence of comorbidity. The occurrence of
comorbidity was associated with higher glucosylated HbA1c values. There was no
difference in the assessment of quality of life regarding gender, age, or the
type of therapy used. The quality of life was assessed as low in patients with
comorbidity. However, certain personality characteristics play a decisive role in
self-evaluation.
PMID- 23155607
TI - [The role of the posterior tibial slope on rupture of the anterior cruciate
ligament].
AB - BACKGROUND/AIM: Posterior tibial slope is one of the most citated factors wich
cause rupture of the anterior cruciate ligament (ACL). The aim of this study was
to determine the association of a greather posterior tibial slope on the lateral
condyle, that is a lesser posterior tibial slope on the medial condyle, with ACL
rupture. METHODS: The patients were divided into two groups. The study group
included the patients with chronic instability of the knee besause of a previous
rupture of ACL. The control group included the patients with knee lesion, but
without ACL rupture. Posterior tibial slope measuring was performed by sagittal
MR slices supported by lateral radiograph of the knee. We measured posterior
tibial slope on lateral and medial condyles of the tibia. Using these values we
calculated an average posterior tibial slope as well as the difference between
slopes on lateral and medial condyles. RESULTS: Patients with ACL rupture have
highly statistically significantly greather posterior tibial slope (p < 0.01) on
lateral tibial condyle (7.1 degrees : 4.5 degrees) as well as statistically
significantly lesser posterior tibial slope (p < 0.05) on medial tibial condyle
(5.9 degrees : 6.6 degrees) than patients with intact ACL. CONCLUSION: Great
posterior tibial slope on lateral tibial condyle associated with the small
posterior tibial slope on the medial tibial condyle, that is a positive
differentce between lateral and medial tibial condyles are factors wich may cause
ACL rupture.
PMID- 23155608
TI - Reliability and relationship of colposcopical, cytological and histopathological
findings in the diagnostic process.
AB - BACKGROUND/AIM: The question about the accuracy of cytology and colposcopy is
more and more asked due to false positive and negative findings on the basis of
which the decision on biopsy is made. The aim of this study was to examine
reliability of biopsies based only on abnormal colposcopical findings, before
receiving the results of Papanicolaou (PA) smear, by comparing findings of
colposcopical, cytological and histopathological (HP) examinations as well as
determining validity of these diagnostic methods. METHODS: The study involved all
patients who had their regular colposcopical and cytological examinations in the
outpatient department during a two-year period (2009-2010) in the Clinic for
Gynecology and Obstetrics, Clinical Center of Serbia, Belgrade. The material for
HP examination was obtained by colposcopically directed biopsy, due to abnormal
colposcopical findings and without waiting for PA smear results. The data
obtained by these methods were statistically analyzed and compared. Furthermore,
validity of colposcopical and cytological examinations was assessed. Results. Out
of 127 patients highly significantly more patients had more malignant cervical
changes on colposcopical exam compared to HP (p = 0.000), and cytological exam (p
= 0.000). Highly significantly more patients had more malignant cervical changes
on PA smear than HP exam (p = 0.000), unless when findings were assessed in the
widest sense of benign and malignant changes when there were no significant
differences in these findings (p = 0.450). Sensitivity of colposcopy as a
diagnostic method was 87.5%, specificity 24.14%, positive predictive value (+PV)
was 34.65% and negative predictive value (-PV) 80.77%. Sensitivity of PA smear as
a diagnostic method was 62.5%, specificity 87.36%, +PV was 69.44%, and -PV
83.52%. CONCLUSION: Regarding the results of our study it is best to make a
decision on treatment according to findings of all the three methods. Cytological
analysis is more reliable than colposcopical examination. Therefore, it is
advisable that following abnormal colposcopical findings, PA smear should always
be taken and only after receiving the results further diagnostics can be planned
(biopsy and HP). A final decision on the therapy has to be made based on HP
findings which are the only method that can give the ultimate reliable diagnosis
of cervical changes.
PMID- 23155609
TI - Contemporary aspects of the diagnostics of alcoholic liver disease.
PMID- 23155610
TI - Electronic health system--development and implementation into the health system
of the republic of Serbia.
PMID- 23155611
TI - [Plastic reorganisation of human motor cortex].
PMID- 23155612
TI - Radionuclide treatment of metastatic disease in patients with differentiated
thyroid carcinoma.
PMID- 23155613
TI - Possibilities of thermovision application in sport and sport rehabilitation.
AB - INTRODUCTION: Infrared thermography or thermovision is increasingly applicable in
sport and sport rehabilitation. Thermic forms, thermic imprints, temperature and
isotherm distribution, temperature gradient change are the terms that are more
and more often met in sport medicine and medicine, in general. CASE REPORT: We
presented two examples of thermovision application: in detection of muscle injury
and changes of the feet exposed to low temperature. In the first example the
thermovision method was used for analysing heat distribution in an athlete with
back muscles injury. With a special original method of local cooling the place
and degree of injury was precisely localized and determined, respectively,
regardless high environmental temperature. In the second case the thermovision
method was for the first time applied in a runner whose feet was exposed to low
temperature. Significant hypothermia of the feet was detected by the method and
appropriate treatment was performed. Thanks to this the athlete had no harmful
consequences. CONCLUSION: Thermovision is fast and efficient in detecting
different kind of injuries, so its increased use in the future can be expected.
PMID- 23155614
TI - Heroin addict with gangrene of the extremities, rhabdomyolysis and severe
hyperkalemia.
AB - INTRODUCTION: Long-time consumption of narcotics leads to altered mental status
of the addict. It is also connected to damages of different organic systems and
it often leads to appearance of multiple organ failure. Excessive narcotics
consumption or abuse in a long time period can lead to various consequences, such
as atraumatic rhabdomyolysis, acute renal failure and electrolytic disorders.
Rhabdomyolysis is characterized by injury of skeletal muscle with subsequent
release of intracellular contents, such as myoglobin, potassium and creatine
phosphokinase. In heroin addicts, rhabdomyolysis is a consequence of the
development of a compartment syndrome due to immobilization of patients in the
state of unconsciousness and prolonged compression of extremities, direct heroin
toxicity or extremities ischemia caused by intraluminal occlusion of blood
vessels after intraarterial injection of heroin. Severe hyperkalemia and the
development of acute renal failure require urgent therapeutic measures, which
imply the application of either conventional treatment or a form of dialysis.
CASE REPORT: We presented a male patient, aged 50, hospitalized in the Emergency
Center Kragujevac due to altered mental status (Glasgow Coma Score 11), partial
respiratory insufficiency (pO2 7.5 kPa, pCO2 4.3 kPa, SpO2 89%), weakness of
lower extremities and atypical electrocardiographic changes. Laboratory analyses,
carried out immediately after the patient's admission to the Emergency Center,
registered the following disturbances: high hyperkalemia level (K+ 9.9 m mol/L),
increased levels of urea (30.1 mmol/L), creatinine (400 micromol/L), creatine
phosphokinase--CK (12,0350 IU/L), CK-MB (2500 IU/L) and myoglobin (57000
microg/L), with normal levels of troponin I (< 0.01 microg/L), as well as signs
of anemia (Hgb 92 g/L, Er 3.61 x 10(12)/L), infection (C-reactive proteine 184
microg/mL, Le 16.1 x 10(9)/L) and acidosis (base excess--18.4 mmol/L, pH 7.26.
Initial examination of the patient revealed swelling and paleness of the right
lower leg, signs of gangrene of the right foot and the 1st and the 4th toes of
the left foot. The patient had normal values of arterial pressure (130/80 mmHg)
and heart rate (64/min(-1)); roentgenographic lungs examination and computerized
tomography (CT) brain examination did not reveal pathological changes in lung and
brain parenchyma; toxicological analyses confirmed the presence of heroin in
patient's organism. The patient was treated by intensive conventional treatment
(infusion of crystalloid solutions, 8.4% solution of sodium bicarbonate, i.v.
infusion of diuretics, calcium gluconate and short-acting insulin), and also by
antibiotics and anticoagulants. Normalization of kalemia and fast regression of
electrocardiographic changes were registered. The patient refused the suggested
surgical treatment (fasciotomy, foot amputation). After stabilization of kidney
function and improvement of his mental state, the patient agreed to undergo
surgical procedure. Therefore, on the day 30 of hospitalization the above-knee
amputation of the right leg was performed, and on the day 38 the transmetatarsal
amputation of the left foot was carried out. After 46 days of hospital treatment,
the patient was released and sent to home treatment. CONCLUSION: The routine
laboratory diagnostics, which implies determining of the levels of potassium,
urea, creatinine and CK in the serum of all hospitalized heroin addicts can
contribute to timely detection of hyperkalemia and acute kidney weakness and
undertaking of appropriate therapeutic measures.
PMID- 23155615
TI - Elevation of troponin values in differential diagnosis of chest pain in view of
pulmonary thromboembolism.
AB - INTRODUCTION: Acute coronary syndrome, as unstable form of ischaemic heart
disease, beside clinical presentation and electrocardiographic abnormalities, is
characterized by increased value of troponin one of cardiospecific enzimes.
Although troponin is a high specific and sensitive indicator of acute coronary
syndrome, any heart muscle injury may induce its increasing, so there are some
other diseases with the increased troponin value. CASE REPORT: We presented a
female patient with chest pain, admitted because of suspicioun of acute coronary
syndrome. Performed coronarography excluded ischemic heart disease. Considering
symtomatology, electrocardiographic abnormalities, increased troponin and D-dimer
values, as well as echocardiography finding we considered pulmonary embolism as a
differential diagnosis, which was confirmed by pulmoangiography. CONCLUSION:
Isolated increased troponin values are not enough for diagnosis of acute coronary
syndrome.
PMID- 23155616
TI - The Spanish flu--part II: the second and third wave.
PMID- 23155617
TI - The Spanish flu (A coment on the article: Radusin M. The spanich flu--part I: the
first wave. Vojnosanit Pregl 2012; 69(9): 812-7).
PMID- 23155618
TI - [Mechanisms of cerebral protection from ischemia by tea constituents].
AB - Epidemiological and clinical studies in recent years have shown that regular
consumption of green or black tea significantly reduces the risk of
cardiovascular diseases, including ischemic stroke. This review presents the
clinical and experimental studies of the antiatherogenic, antiplatelet,
antioxidant, antiinflammatory and other mechanisms of action of tea and
substances in its composition. Effects of tea and its components, are described
after long-term, and a short-term consumption. The role of catechins and specific
amino acid L-theanine in the possible mechanisms of protection against
cerebrovascular disease are discussed.
PMID- 23155619
TI - [Phenomenon of heart ischemic postconditioning].
AB - Authors of review analyzed papers on problem of heart ischemic postconditioning.
In the review, it was demonstrated that postconditioning decreased an infarct
size, prevented cardiomyocytes apoptosis, improved cardiac contractility in
reperfusion period, augmented cardiac tolerance to arrhythmogenic impact
ofreperfusion, prevented neutrophil invasion into the reperfused heart, abolished
reperfusion endothelial dysfunction and suppressed reperfusion oxidative stress
in myocardium.
PMID- 23155620
TI - [Free radical modification of proteins in brain structure of Sprague-Dawley rats
and some behaviour indicators after prenatal stress].
AB - We studied the influence of late prenatal stress on free radical oxidation
processes in Sprague-Dawley rats cortex, striatum, hippocampus, hypothalamus
proteins. It was shown that after prenatal stress most changes were observed in
hypothalamus and hippocampus. It was shown that in hypothalamus spontaneous
oxidation level increased, but level of induced oxidation decreased, the opposite
changes were found in hippocampus. Simultaneously minor changes of protein
modification were observed in cortex and striatum. It was shown that prenatal
stress changed both correlation of proteins free radical oxidation in studied
structures and values of these data regarding to control. In test of "open field"
motor activity in rats after prenatal stress decreased and time of freezing and
grooming increased; opposite, in T-labyrinth motor activity and time of grooming
in rats after prenatal stress increased, but time of freezing decreased.
PMID- 23155621
TI - [Physiological effects induced by dermorphin synthetic analogue--opilong].
AB - The effects of repeated opilong injections in a dose of 50 microg/kg/day on
subsequent learning of Wistar rats have been studied. The substance caused
significant anxiolytic and analgesic effects, as the majority of animals could be
learned (90% against 40% in control group) despite of painful stimulus preceding
to education. Opilong in a small dose displaced a relation of excitatory-inhibit
processes to significant prevalence of excitation although the substance was
already absent in an organism for a long time. Raised peripheral sensitivity in
all rats, provoked by opilong, correlated with CNS hyper excitability, expressed
in stressful, neurotic psychoemotional reactions and in the form of active
avoidance. The biochemical blood analysis in opilong-induced rats demonstrated
the attributes of prethrombosis in the form of fibrinolysis depression and
hypercoagulation. A view is expressed, that the neuromediator brain systems can
be the basic point of opilong action, that are responsible for the excitatory
inhibit conditions of CNS functioning referred on maintenance of conditioned
field stability.
PMID- 23155622
TI - [Immunohistochemical study of CART-peptide in striato-nigral projections at
dopamine loss].
AB - The increase of CART-peptide optical density was found immunohistochemically in
nucleus accumbens neurons and in their terminals in substantia nigra in Wistar
rats after 28% reduction of dopaminergic neurons in a substantia nigra (in the
model of lactacystin induced proteo some disfunction). At the same time after in
vitro incubation of nigro-accumbal brain slice with AMPT (alpha-methyl
paratirosine--dopamine inhibitor) for 4 h the reduction of tyrosine hydroxylase
optical density (the enzyme limiting dopamine synthesis) in substantia nigr
neurons was found and optical density of CART-peptide in nucleus accumbens and
substantia nigra was also revealed. In both experiments data about activation of
CARTergic neurons in stria to-nigral projections testifies on participation of
CART-peptide in compensatory brain mechanisms at dopamine loss and its role as
modulator of dopaminergic brain neurons functional activity.
PMID- 23155623
TI - [The impact of early and late ischemic preconditioning on brain damage and degree
of neurological deficiency in rats].
AB - The present study was aimed to investigate neuroprotective effects of early and
late ischemic preconditioning in the acute phase of ischemic brain damage in
rats. It was found that a single five-minute ischemic episode of early ischemic
preconditioning did not lead to significant neuroprotective effects in comparison
with control group, while three five-minute ischemic episode early ischemic
preconditioning accompanied by a significant increase in neurological deficit and
growing damage rate in CA1 hippocampus neurons. In contrast, later ischemic
preconditioning in form of single five-minute episode 24 hours before ischemia
modeling, provided a significant neuroprotective effect, manifesting reduced
neurological deficit and maintaining viability of CA1 hippocampus neurons.
PMID- 23155624
TI - [Liver phospholipids composition and activity of glutathione redox-system in rats
on prolonged high-fat diet].
AB - We studied liver phospholipid composition and activity of the glutathione redox
system in rats on prolonged for 180 days high-fat diet. The adaptive response was
formed from day 30 to day 90 of high-fat load and was associated with increased
relative content of phosphatidylseryne and phosphatidylethanolamine homeostasis.
Constant antioxidant activity of glutathione redox-system for 30 days period of
high-fat load was achieved by stable glutathioneperoxidase activity, on 90th day-
level of glutathione reductase increased. The detected fluctuations in
phospholipid composition and activity of glutathione redox-system in liver tissue
on 30-90th days of the experiment indicated the formation of a compensatory
response to maintain cell integrity. On 180th day of high-fat load due to
exhaustion of compensatory mechanisms in the glutathione antioxidant defense and
intensification of lipid peroxidation the lipid matrix of cytomembrane underwent
profound restructuring associated with decreased levels of phosphatidylinositol,
phosphatidylethanolamine, increased proportion of apoptotic phospholipids
(phosphatidylserine, sphingomyelin). Such phospholipids composition on the
background of glutathione redox-system inhibition can determine apoptosis,
necrosis and liver fibrogenesis. These results extend the knowledge about
mechanisms of liver adaptation and disadaptation to nutritional stress.
PMID- 23155625
TI - [Effect of alpha2-adrenergic receptor antagonist yohimbine on thermoregulatory
responses to cooling].
AB - Ionoforetic yohimbine application to skin has a modulating effect on the
thermoregulatory parameters. In thermoneutral conditions, yohimbine increases
heat production and heat dissipation. At subsequent cooling, yohimbine
facilitates the initiation of vascular and metabolic response by reducing the
temperature threshold of both nonshivering and shivering thermogenesis. Under the
influence of yohimbine the maximum value of both vascular and metabolic response
increases. In strengthening the metabolic response the skeletal muscles shivering
significantly contributes. In contrast to yohimbine, the norepinephrine
thermogenic effect occurs by strengthening nonshivering thermogenesis. Features
of the yohimbine influence on thermoregulatory parameters due to the dual
localization and function of the alpha2-adrenergic receptors.
PMID- 23155626
TI - [Opioid peptides effect on lipid peroxidation in long-term stress].
AB - It was shown in rats, that injection of opioid peptides (dynorphin A (1-13),
DSLET and DAGO) decreased the stress-induced activation of lipid peroxidation in
liver tissue and plasma. Dynorphin A (1-13) manifested the most expressed
antioxidant effect in liver tissue. It not only decreased lipid peroxidation
metabolites concentration, but also increased superoxiddismutase and catalase
activity. Other peptides did not interfere enzyme activity. The use of DSLET or
DAGO increased the superoxiddismutase plasma activity. Dynorphin A (1-13)
injection increased catalase activity, but not superoxiddismutase. These effects
could be explained by peculiarities of opioid receptors spread in liver tissue
and stress-limiting action of peptides in entire organism.
PMID- 23155627
TI - [Exenatide stimulated solute-free water excretion by human kidney].
AB - Exenatide effect was studied in 55 human including 38 patients with type 2
diabetes mellitus without signs of diabetic nephropathy and primary renal
diseases. Preliminary study with water load in volume from 0.5 to 1% b.w. showed
that water load equal to 0.7% b.w. caused significant increase in urine
excretion. The rise of diuresis after 10 microg Byetta (exenatide) injection and
simultaneous water load of 0.7% of b.w. depended on increase in solute-free water
clearance. Thus, exenatide (mimetic of GLP-1) action let us to consider its
possible role as component of osmoregulation system in human. This peptide
provides high efficiency of renal function in osmotic homeostasis.
PMID- 23155628
TI - [M1 and M2 macrophage phenotypes functional activity as essential components in
innate immune response assessment].
AB - Macrophage capacity to phagocytosis and migration activity are crucial components
in innate immune response assessment. Differences in functional responses of two
macrophage phenotypes were detected. Phagocytic activity of proinflammatory
alveolar M1 phenotype in relation to S. aureus is more expressed than of
antinflammatory M2 phenotype. Comparative analysis of migration activity showed
alternative dependence of migration index on the type of used chemoattractant.
PMID- 23155629
TI - [Terminology of umbilical access surgery: a new Babel?].
PMID- 23155630
TI - [Cold-knife retrograde endoscopic endopyelotomy (Cutting-Balloon) in children
with ureteropelvic junction obstruction: early results].
AB - BACKGROUND: To present our early experience in the use of Cutting-Balloon for the
treatment of resistant or relapsed ureteropelvic junction obstruction (UPJO)
after a prior endourological retrograde high-pressure balloon dilatation (RHPBD).
MATERIALS AND METHODS: Patients with progressive hydronephrosis and impaired
drainage of the renal pelvis on a diuretic renal scan were treated with RHPBD. In
those patients with resistant UPJO (waist persistence after dilatation) or
relapsed UPJO, we consider using a Cutting-Balloon as an alternative to our
current protocol (second RHPBD or open surgery). A JJ stent was placed following
the procedure, and removed at 4-6 weeks. Outcomes were evaluated 3 and 6 months
after stent removal, and every 6 months thereafter, repeating renal
ultrasonography and diuretic renal scan. RESULTS: Between 2008 and 2010 we
treated with Cutting-balloon 5 patients (4 male, 1 woman) with UPJO (left side: 3
cases, right side: 1 case, bilateral: 1 case) with a mean age of 3 months (range,
10 days to 7 months). Four cases had resistant UPJO and 1 case relapsed UPJO.
After the procedure, and during the follow-up period of 12 months (range, 9-18
months), no further treatment was necessary. Four patients had improvement of
hydronephrosis, with normal relative renal function (RRF). One patient (RRF 18%
before treatment) did not improve. No periprocedural complications occurred.
CONCLUSIONS: Cutting-balloon retrograde endopyelotomy seems to be a treatment
with encouraging early results for resistant and relapsed UPJO, after a prior
RHPBD. We believe that further clinical evaluation is needed to confirm these
findings.
PMID- 23155631
TI - [Ovarian cryopreservation in girls with cancer: new challenges].
AB - BACKGROUND: Ovarian cortex cryopreservation (OCC) for future autotransplant
represents a treatment alternative for those paediatric cancer survivors affected
of ovarian failure and fertility disorders. METHODS: Patients with high
gonadotoxic risk are included in the Oncology Paediatric Fertility Preservation
Programme: those receiving pelvic radiotherapy, bone marrow transplantation, high
doses of cranial radiotherapy or alquilating agents, or those with bilateral
ovarian pathology. Prior to the oncological treatment, the ovarian tissue is
harvested laparoscopically. At the same time, other invasive procedures are done.
Once malignancy is ruled out of the specimen and the presence of primordial
follicles is confirmed, the multidisciplinary team of oncologist, paediatric
surgeon and fertility specialist coordinate the processing and delivery of the
ovarian cortex to the Comunidad Valenciana Tissue Bank. RESULTS: From July 2008
to May 2010 eight patients have been included in the programme, aged between 8-18
years old and with diagnosis of: Hodgkin's lymphoma (n= 2), Acute Myeloblastic
and Lymphoblastic leukaemia (n= 2), pelvic Ewing's sarcoma, bilateral ovarian
Teratoma and Meduloblastoma. Five patients underwent non gonadotoxic chemotherapy
before OCC. Six additional procedures were done using the same anaesthetic event.
Partial oophorectomy was performed in half the cases, total oophorectomy in the
rest of them, and an ovarian pexia was once associated. All taken samples were
found to be valid. CONCLUSIONS: OCC of selected patients was performed safely,
with neither postoperative complications nor delay of the oncological treatment.
Therefore, the first national experience in this procedure has been
satisfactorily achieved.
PMID- 23155632
TI - [Preliminary results in the correction of the pectus excavatum with the Acastello
modified Welch technique].
AB - BACKGROUND: Congenital malformations of the chest wall are a heterogeneous group
of diseases affecting the costal cartilage, ribs, sternum, scapula and clavicle.
The pectus excavatum is characterized by a posterior depression of the sternum.
Acastello-Welch technique consists in a partial resection of the costal
cartilages adding some bars or plates unilaterally fixed to the sternum in each
hemithorax. MATERIALS AND METHODS: From October 2008 to March 2011 we evaluated
108 patients with congenital malformations of the chest wall. Forty-seven
patients (44%) had a pectus excavatum and 12 were treated with Acastello-Welch
technique. RESULTS: There were no intraoperative complications. After a mean
follow up of 27 months, correction of the deformity was very satisfactory both
objective and subjective for patients. CONCLUSIONS: The Welch thoracoplasty
modified by Acastello is a good option for the correction of the pectus excavatum
associating little morbidity and good esthetic outcomes.
PMID- 23155633
TI - [Subcutaneously inserted central intravascular devices in the pediatric oncology
patient: can we minimize their infection].
AB - Long-term indwelling central venous access devices are frequently used in
pediatric patients. Their main complication is infection, that can even mean
their removal. We try to identify the risk factors really involved in this
complication and in their removal. We have made a retrospective review of 120
oncologic pediatric patients who received a central venous device between 2003
and 2009. We searched for epidemiologic, clinic, microbiologic and surgical risk
factors. We made a comparative data analysis among: GROUP A, children who
suffered device infection, GROUP B the others. Group A was divided into early
infection (first month after implantation)/late infection, removed/not removed.
Data were analized with statistical program SPSS. 29 suffered from leukemia, 19
from lymphoma and the main part, 72, from solid tumour. 31% experienced infection
(GROUP A), being early in the 36% of them. 16% had to be withdrawn. Data analysis
revealed statistical association with the age (p=0.015) and with the reception of
chemiotherapic treatment the week before the surgical insertion. The rest of the
studied factors did not revealed a real association, but could be guess a
relationship among infection and leukemia, subclavian catheters, those patients
whose deviced was introduced using a guide over a previous catheter and also
transplanted. Related to early infection the only associateon founded was with
the subclavian access (p=0.018). In conclusion, in our serie long-term central
venous access infection was more frequent in the younger patients and also in
those who had received chemotherapy the week before the catheter implantation.
The tendency towards infection in leukemia, transplanted and subclavian carriers
has to be studied in a prospective way with a larger number of oncologic
children.
PMID- 23155634
TI - [Spanish pediatric research in MEDLINE].
AB - The objective of this work was to elaborate and apply search filters to retrieve
the Spanish scientific output (SO) in pediatrics. A bibliographic search was
carried out in MEDLINE. The search was based on the construction and application
of a Spanish geographic filter, elaborated according to a previous model, and a
thematic one to retrieve records in the pediatric area. The following was
determined: frequency of the records, place of publication, language, journal,
number of authors and year of publication; to observe the dynamics of the SO, a
bibliographic study was carried out over a period of ten years. By applying the
geographic filter, 277,949 records were retrieved; 620 were retrieved in the
pediatric Spanish area. Of these, 262 (42.26%) were published between 2000-2009.
Most of records were signed by one author. In Spain, the records were published
in 42 journals and abroad in 79 journals. A search filter able to retrieve the
pediatric Spanish SO was created, that supposed 1.22% of the total records in the
pediatric field encompassed by MEDLINE. Approximately 80% of these articles were
published in Spain.
PMID- 23155635
TI - [Is experimental surgery necessary or essential in the training program of a
pediatric surgeon?].
AB - Many surgical procedures performed in pediatric surgery have a slow learning
curve, the volume of patients and the existence of complex diseases that require
extensive training and surgical skill, have taken our service to create a global
training program of experimental surgery. This program based on the simulation
and training invasive procedures in real anatomical models, aims to educate our
residents in a global and efficiently way in order to obtain an improvement of
technical training, and increased patient safety result of experience and
expertise wined in the experimental animal. This paper presents the main
features, objectives and results obtained with this training program and seeks to
promote the incorporation of simulation programs in live animal as an essential
part of the training of pediatric surgery resident.
PMID- 23155636
TI - [Robotics in pediatric surgery].
AB - Despite the extensive use of robotics in the adult population, the use of
robotics in pediatrics has not been well accepted. There is still a lack of
awareness from pediatric surgeons on how to use the robotic equipment, its
advantages and indications. Benefit is still controversial. Dexterity and better
visualization of the surgical field are one of the strong values. Conversely,
cost and a lack of small instruments prevent the use of robotics in the smaller
patients. The aim of this manuscript is to present the controversies about the
use of robotics in pediatric surgery.
PMID- 23155637
TI - [Initial experience in single site laparoscopic surgery in a pediatric hospital
of Bogota].
AB - BACKGROUND: Minimally invasive surgery is the current accepted approach for
abdominal surgery. However, less invasive techniques such as single incision
laparoscopic surgery (SILS) are being used more frequently and we believe it will
become the standard choice for abdominal surgery. This report describes our
initial experience with Single Port Incision Surgery (SILS). METHODS: We reviewed
all the patients who underwent SILS in our hospital between November 2009 and
July 2011. We used a surgical glove attached to a wound retractor to yield a
multi-port hybrid. RESULTS: We present 80 patients with a mean age of 8.6 years
and mean weight of 32,1 kg. The youngest patient was 8 days old and the smallest
patient weighed 2.5 kg. The average duration of surgery was 48.2 minutes. The
average length of stay was 48.7 hours. Different procedures were performed:
appendectomies for early appendicitis (55%), hepatic biopsies (15%),
appendectomies for perforated appendicitis (7.5%), and the following isolated
cases: cholecystectomy, Meckel's diverticulum resection, oophorectomy, salpingo
oophorectomy, ovarian cystectomy, bowel biopsy, and a resection of an accessory
spleen torsion. SILS was successfully completed in 78 cases, and 2 cases were
converted to standard laparoscopy and none to open surgery. There were no
intraoperative surgical complications. Postoperative complications presented in 5
cases: a superficial incisional site infection, two residual abdominal abscesses,
one bowel obstruction and one evisceration. The last two cases subsequently
resulted in reoperation and occurred early in our learning curve. CONCLUSIONS:
SILS is a reproducible and viable technique that may be used successfully in
pediatric surgery. It may be used safely in different procedures and age groups,
even in neonates. Time of surgery decreased with our learning curve.
Additionally, excellent cosmetic results were obtained as evidenced by
imperceptible umbilical scarring.
PMID- 23155638
TI - [Our experience in retroperitoneoscopic total or partial nephrectomies].
AB - The retroperitoneal laparoscopic approach is displacing open surgery and
transperitoneal approach for several benign renal conditions. In the past 6 years
we have performed 20 procedures, 10 with lateral position and 10 with posterior
prone one: 13 total nephrectomies and 7 heminephrectomies in children aged 4,1
years on average. Mean operative time was 200 minutes in partial procedures and
278 in the total ones. Oral feeding was restored to 11,4 hours and average
hospital postoperative stay was 1,58 days in total nephrectomies and 2,18 in
heminephrectomies. There was no intraoperative bleeding. Complications were two
urine leaks, two infections due to residual ureteral stumps and a case of
transient hematuria. There were no significant differences between posterior and
lateral approaches as to hospital stay, time of onset of oral feeding or
complications, although the average operative time was shorter in the posterior
approach (mean 170 min, SD 17,3) than in the lateral one (mean 216 min, SD 41)
(P=0,024) in total nephrectomies. Retroperitoneoscopy allows a safe access to the
kidney and avoids morbidity associated with the transperitoneal access. The
posterior approach provides better vascular control, maintains the peritoneum far
and allows the procedure with fewer ports, maximizing work space.
PMID- 23155639
TI - [Laparoscopic nephroureterectomy in Wilms tumor].
AB - INTRODUCTION: Minimally invasive surgery (CMI) for the treatment of malignant
tumors in children begins to have a role for selected cases and reaches similar
results than open surgery. We show our first two cases of Wilms tumor treated by
laparoscopy describing patients and technique. MATERIAL AND METHODS: Three-year
old girl with macroscopic hematuria is diagnosed of 8 cm mass in the left kidney
suggesting Wilms tumor. After 4 weeks of chemotherapy she went under laparoscopic
nephroureterectomy. The histological result was Wilms tumor. Chemotherapy was
completed seven more months. Five-year-old patient with abdominal pain is
diagnosed of renal right mass suggesting Wilms tumor. After 4 weeks of
chemotherapy the laparoscopic nephroureterectomy was performed. The histological
result was Wilms tumor. Treatment was completes with postoperatory chemotherapy.
RESULTS: After 1 year follow-up both patients have clinical and radiological
absence of disease. CONCLUSION: The CMI in selected cases of Wilms tumor fulfills
successfully the aims of the surgical treatment.
PMID- 23155640
TI - [Heterotaxy-polysplenia, approach to the esophageal hiatus for Nissen technique].
AB - INTRODUCTION: Heterotaxy is a failure in embryonic development to achieve left
right symmetry. OBJECTIVE: To report a case of heterotaxy and show a surgical
approach for fundoplication. MATERIAL AND METHODS: A girl with heterotaxy
polysplenia syndrome with gastroesophageal reflux and recurrent abdominal pain.
It was decided to perform laparoscopic antireflux treatment with Nissen
fundoplication with approach by the right side of the diaphragmatic hiatus and
pillars. CONCLUSIONS: Surgery is being discussed in these syndromes, indicating
only in cases of recurrent abdominal pain, subocclusive lesions or when diagnosis
of gastroesophageal reflux is done. The dilemma is between laparoscopic or
classical laparotomy. The main difficulty of the laparoscopic approach is the
enlarged liver and stomach placement right despite the esophageal hiatus is
normally on the left side.
PMID- 23155641
TI - [Training of pediatric surgeons in the dawn of the XXI century].
PMID- 23155642
TI - [Traumatic diaphragmatic hernia: a vital need for an early diagnosis].
AB - INTRODUCTION: Traumatic diaphragmatic hernia (HDT) is exceptional in children.
Its diagnosis is usually delayed for appearing in the context of severe
polytrauma. The aim is to analyze our series in relation to the severity scores.
PATIENTS AND METHODS: Five patients with HDT are presented. Age, biomechanics,
clinical, ISS (injury severity score), ITP (pediatric trauma index), GCS (Glasgow
coma scale), RTS (Revised Trauma Score) and treatment were studied. The
probability of survival (Ps) was calculated with the TRISS method, Ps = 1/(1 +
eb), b = b0 + bl (RTS) + b2 (ISS) + B3 (age). RESULTS: There were two males and
three females, mean age was six years old (range = 3-10). Traffic accident was
the mechanism of the thoracoabdominal trauma in 80% and one was crushed by garage
door. The affected side was right in two cases and left in three. Mean ISS was 41
(range = 32-57), ITP 6 (range = 2-9) and RTS 6.1 (range = 5.1 to 6.9). The main
symptom was respiratory. Plain chest radiography was diagnostic in three
patients, one by CT scann, and another was a finding at laparotomy. Two had liver
herniation, one had tension gastrothorax and two had gastric perforations. All
patients underwent surgery through the abdomen. Estimated survival by the TRISS
method was respectively 86.6%, 78.2%, 57.2%, 84.7% and 57.1%, while the actual
was 100%. One has a severe disability. DISCUSSION: To study the biomechanics and
semiology is essential in the early diagnosis of TDH in pediatric polytrauma and
suspect it is mandatory prior to realize percutaneous chest procedures. The TRISS
method has a great importance to assess the adult polytrauma, but specific scores
are needed for children.
PMID- 23155643
TI - [Estimation of the risk of upper digestive tract bleeding in patients with portal
cavernomatosis].
AB - PURPOSE: The aim of this study is to find out the risk of upper gastrointestinal
bleeding (UGB) after the diagnosis of portal cavernoma in children, and to
investigate several potential risk factors. MATERIAL AND METHODS: We analyzed
retrospectively 13 cases of portal cavernoma and estimated the risk of UGB with
the Kaplan-Meier survival analysis. We calculated the incidence rate of the
sample and the number of haemorrhages per year for each patient individually.
From the moment of the diagnosis various parameters were recorded: age,
platelets, leukocytes, hemoblobin, hematocrit, prothrombin time and number of
bleedings. The relation between these parameters and the risk of bleeding was
assessed with the Cox analysis. RESULTS: The patients were followed for a median
period of 7.1 years. 10 patients (77%) presented at least 1 episode of UGB after
the diagnosis. The median survival time until the first haemorrhage was 314 days.
After the diagnosis the incidence rate of the sample was 0.43 episodes of upper
gastrointestinal bleeding per person-year. The number of individual bleedings per
person had a range of 0-2.2 episodes per year. CONCLUSIONS: There is very few
data about the risk of bleeding in children with portal cavernoma. In our sample,
we found out an incidence rate of 0.43 and a median survival time of 314 days
until the first episode of bleeding after the diagnosis, but we were not able to
find a statistically significant association between the studied variables and
the risk of bleeding.
PMID- 23155644
TI - [Generation of a substitute for human oral mucosa and verification of its
viability by tissue-engineering].
AB - Reconstruction of large oral mucosa defects is often challenging, since the
shortage of healthy oral mucosa to replace the excised tissues. This way, tissue
ingineering techniques may provide a source of autologous tissues available for
transplant in these patients. In this work, we have developed a new model for
artificial oral mucosa generated by tissue engineering using a fibrin-agarosa
scaffold. For that purpose, we have generated primary cultures of human oral
mucosa fibroblasts and keratinocytes from small biopsies of normal mucosa oral
using enzymatic treatments. Then, we have determined the viability of cultured
cells by electron probe quantitative X-ray microanalysis, and we have
demonstrated that most of the cells in the primary cultures were alive and hd
high K/Na ratios. Once cell viability was determined, we used cultured
fibroblasts and keratinocytes to develop an artificial oral mucosa construct by
using a fibrin-agarosa extracellular matrix and a sequential culture technique
using porous culture inserts. Histological analysis of the artificial tissues
showed high similarities with normal oral mucosa controls. The epithelium of the
oral substitutes had several layers, with desmosomes and apical microvilli and
microplicae. Both the controls and de oral mucosa substitutes showed high
suprabasal expression of cytokeratin 13 and low expression of cytokeratin 10. All
these results suggest that our model of oral mucosa using fibrin-agarose
scaffolds show several similarities with native human oral mucosa.
PMID- 23155645
TI - [Comparative analysis between the Seldinger technique vs. open dissection in the
implantation of intravenous reservoirs].
AB - OBJECTIVE: To analyze advantages and disadvantages between Seldinger's technique
(ST) and surgical dissection (SD) on intravenous port-a-caths comparing surgical
parameters as time and complications. MATERIAL AND METHOD: An analytic
retrospective study involving historic cohorts was realized, comparing our
surgical experience on port-a-cath implantation with Seldinger technique or
surgical dissection. Statistical analysis was made reflecting clinical and
surgical parameters, such as surgical time length and intra/postoperative
complications. RESULTS: 193 Port-a-caths were analyzed (119 SD, 74 ST), mainly
placed for chemotherapy treatment (83.41%). Surgical time length expended at
single procedures was 72.85 +/- 29.35 minutes for SD and 62.83 +/- 20.08 minutes
for ST (p < 0.05). There were none operator-dependent differences. Statistically
significant differences were not found between the two cohort's populations,
neither at complications percentages. Greater-sized port-a-caths presented a
higher average of skin necrosis (p > 0.05) however, lower-sized port-a-caths
showed a higher average of infection (16% upon 7.7% p > 0.05). Both ST (51.67 vs.
98.14 min) and SD (78.56 vs. 123.61 min) showed lower surgical time length at
left venous accesses (d = 171 vs. i = 19). Average in days for the extraction of
port-a-caths with regard to complications was 121 days. CONCLUSION: Seldinger
technique reduced the definitive lost of surgical dissected venous accesses,
being possible further utilization of the same vein for subsequent port-a-caths.
Seldinger technique reduces surgical time length without increasing
complication's rate. Left venous access does not imply higher surgical time
length. Complications may be related with port-a-cath's size.
PMID- 23155646
TI - [Very severe hepatic trauma in childhood. The report of two cases with minimally
invasive treatment].
AB - Liver trauma in children is a pathology that has an increasing incidence mainly
due to the implications of growing children in hazardous games and sports
adventure, and the frequent car accidents. There has been a shift of management
in haemodynamically stable patients towards non-operative management. This allows
in most cases a patient's complete recovery without surgical aggression,
preventing further damage derived from the handling of the injured liver.
Herewith we report two cases of a 6 and 4 year old boys who suffered a very
severe traumatic rupture of the liver. They were operated through minimally
invasive surgical procedures, achieving complete resolution of the serious
damages.
PMID- 23155647
TI - [Evaluation of urodynamics and continence in bladder augmentations with
sigmoids].
AB - AIM: To evaluate our experience in sigmoid augmentation to manage renal upper
tract dilatation and urinary incontinence. MATERIAL AND METHODS: Retrospective
descriptive study of the augmentation cystoplasties with sigmoid patch. We
analyze clinical, urodinamic and surgical parameters. RESULTS: We have make 30
cistoplasties with a mean age of 10.24 years (3-15 years) with a mean follow up
of 8 years (9 months-15 years). The main diagnosis was neurogenic bladder (63,3%)
being the main indication for the augmentation the progressive dilatation of the
renal upper tract (43,3%). We associate to the procedure the collocation of an
artificial sphinter (30%), Mitrofanoff or ureteral reimplantation. There was no
major complication. In the urodinamics, the bladders had low capacity, high
pression and low compliance. After surgery, urodinamic parameters improve. During
follow up, continence improve with more intermittent clean catheterism (median
4/day). Vesical lithiasis was more common late complication with nor acute
abdominal surgical illness nor malignancy; 2 patients finished in renal
transplantation. Evolution was positive in 66%, and negative in 18,5%.
CONCLUSIONS: Sigmoid augmentation cystoplasty is a good technique, that allows
urodinamic and continence improvement. The conscience in the importance of
intermittent catheterisms reduces the incidence of complications.
PMID- 23155648
TI - [Surgical risk scale in pediatric surgery].
AB - INTRODUCTION: The need to measure the level of surgical risk arises from its
direct relationship with the development of postoperative complications and the
use of hospital resources. The construction of a surgical risk scale (ERQ) for
pediatric surgery should be based on a common language, by using a small number
of easy to collect and reproduce variables. The objectives of this study were to
construct an ERQ for pediatric patients and to analyze the surgical performance.
MATERIALS AND METHODS: We retrospectively analyzed 105 primary surgical
procedures under general anesthesia performed by liver transplantation service at
Hospital Garrahan, between 29/6/08 and 25/3/10. Newborn patients were not
considered. The ERQ was built by adding patient risk factors (PRL): weight (< o >
10 kg), co-morbidities (coagulopathy-obesity-diabetes) and life support; and the
magnitude level of the surgical procedure (SPL): surgical time and requirement of
blood transfusions. The surgical performance was considered as a relation between
the level of surgical risk and the post-operative results, measured with the
classification of surgical complications proposed by Clavien et al (STROC). The
main end point of the study was the STROC > or = 3 (severe complications). The
ERQ predictive power for serious complications was compared with the anaesthetic
risk (ASA). Descriptive and analytical statistics took place. The predictive
value for complications was calculated by means of a ROC curve. The estimation of
the risk was calculated by relative risk. RESULTS: The ERQ was constituted on a
continuum of 6 risk levels (2 to 7). The ROC's curve predictive power to
determine the development of severe post-operative complications (STROC > or = 3)
was 0.87 (CI 0,80-0,94) for the ERQ and 0.81 (CI 0,73-0,89) for the ASA. Level of
> or = 5 of ERQ was the cut-off point that better predicted the development of
STROC > or = 3. CONCLUSION: The ERQ is an easy tool, useful to quantify and
compare surgical risks and results. It showed a high predictive power of
postoperative complications.
PMID- 23155649
TI - [Botulinic toxin type A in the treatment of children with neurogenic bladder].
AB - INTRODUCTION. Botulinum toxin A (BoNTA) is an alternative in children with
neurogenic bladder refractory to anticholinergics. OBJECTIVE. To evaluate the
initial effects of BoNTA in neurogenic bladders. PATIENTS AND METHODS 12 patients
(9 myelomeningoceles, 1 tethered cord, 1 medullary astrocytoma, 1 Ewing's
sarcoma) were studied. The pretreatment evaluation included: voiding diary,
incontinence score, renovesical ultrasound, cystourethrography and urodynamic
parameters. Patients received 300 UI of BoNTA via detrusor injections. They were
re-evaluated at months 1, 3 and 6. After the third control, if improvement was
confirmed, patients were injected again. Otherwise, surgery was indicated.
RESULTS: After the initial injection, 50% of patients achieved complete
continence and 20% remained with minimal leaks. The mean maximum bladder capacity
increased from 264 +/- 117 ml to 324 +/- 170 ml (P = 0.322). The mean detrusor
pressure decreased from 46 +/- 17 cm H2O to 42 +/- 14 cm H2O (P=0.596). The mean
bladder compliance increased from 7.6 +/- 5.9 ml/cm H2O to 10.4 +/- 6.4 ml/cm H2O
(P = 0.290). The reflex voiding contractions disappeared in 2 patients; 8
presented trabeculae. Ten patients were reinjected and two underwent surgery.
CONCLUSION: 70% urinary continence was achieved after the initial injection. No
significant urodynamic changes were observed. A longer follow-up with subsequent
injections is needed.
PMID- 23155650
TI - [Correction of the complicated pectus excavatum with extracorporeal circulation
(ECC) support].
AB - INTRODUCTION: The most serious complication in surgery of the pectus excavatum is
the possible cardiac perforation. After its resolution, it is very likely that
the relapse of the excavatum will be more severe due to the intense retrosternal
fibrosis generated, involving cardiac structures and fixing them to the sternum.
Reintervention requires modifications of the usual techniques and special
monitoring due to the increased risk of cardiac and large vessel lesions. We
present the case of 2 patients with severe pectus excavatum with a previous
attempt for correction with cardiac perforation. CLINICAL CASES: Case 1. A 16
year old male with Haller index 9.9, diagnosed of Ehlers-Danlos syndrome and
operated on in neonatal period of cardiac disease, with previous attempt for
correction using the Ravitch technique that relapsed and cardiac perforation
during it. Case 2. An 11 year old girl, with background of diaphragmatic hernia
and cardiac perforation on introducing the Nuss bar at 5 years of age, with
Haller index 5.5. Both were operated on under ECC with the collaboration of the
Cardiac Surgery Service and cardiac adherences were released after median
sternotomy. After it, the Nuss bar was introduced and then sternal closure was
performed with reinforced steel wires with titanium plates in the anterior and
posterior part. DISCUSSION: The backgrounds of the cardiac approach complicate
the intervention for the correction of the pectus excavatum, with a high risk of
cardiac trauma. Counting on the support of the cardiac surgery and the ECC, we
achieve an adequate control and prediction of the complications
PMID- 23155651
TI - [Minimally invasive surgery in pediatric patients with ventriculo-peritoneal
shunts].
AB - The use of laparoscopy in patients with ventriculo-peritoneal shunts has been
controversial. There is concern about the risk malfunction or infection of the
shunt as well as about the possibility of adhesions that could make the surgical
procedures too difficult to be undertaken by minimally invasive surgery. We
present our results in pediatric patients with ventriculoperitoneal shunts that
have undergone laparoscopic procedures in our department. We have performed 16
surgical procedures. The most frequent indication was fundoplication. During
surgery there were no complications or intracranial hypertension episodes. Two of
the procedures were considered by the surgeons more difficult and longer than
usual. None of them required conversion to open technique. One shunt had to be
replaced after surgery because of infection. According to our experience
minimally invasive surgery is feasible and safe in pediatric patients with
ventriculo-peritoneal shunts.
PMID- 23155652
TI - [Phimosis: dorsal slit or circumcision?].
AB - INTRODUCTION: Phimosis is perhaps one of the most frequent consultation on
pediatric surgery clinics throught the world. The aim of this study is to compare
the two procedures more frequently performed in our hospital: dorsal slit and
circumcision. PATIENTS Y METHODS: Retrospective study of 1698 patients who were
admitted for elective surgical treatment of phimosis between 2003 and 2009. We
analyzed age, surgical and anesthethic times, surgical technique and
complications. We also did transversal descriptive study through telephonic
survey on parents and patients older than 16 years old. RESULTS: There was 76.6%
of dorsal slit (n = 1300) and 23.4% (n= 398) of circumcisions. Mean age was 7.15
years y mean time of follow up was 42.3 months. Surgical time was significantly
higher in circumcision (p < 0.0001). There were 3% (n = 51) of reoperations, no
differences between groups. We didn't find differences in postoperative stenosis,
but bleeding was more frequent in circumcision group (1.7%; p = 0.03). There were
no differences on parental appreciation of postoperative pain, or functional and
esthetic satisfaction between groups. CONCLUSIONS: We didn't find differences on
subjective satisfaction between groups. Even if there are differences n
postoperative bleeding, global incidence is very low. In our experience both
techniques are valid and safe, so surgeon and parents must jointly make the
decision.
PMID- 23155653
TI - [Venous embolization--treatment of choice in varicoceles].
AB - Varicocele consists of the varicose expansion of the spermatic vein. It's more
frequently in the left side (10:1) as consequence of an evil functioning or
absence of the valves of the spermatic left vein. Between March 1999 and December
2009 there have been gathered a total of 37 cases diagnosed of varicocele in the
pediatric population of our center. After a local anesthetic we created a femoral
aproach. We advance into the left renal vein using a catheter Simmons type I and
then we position the top of the catheter beyond the ostium of the spermatic vein
to fulfil the renal left vein by means of the administration of contrast iodized
and gonadal vein could be visualized using retrograde phlebography. Transcatheter
embolization will carry out across the introduction of coils (approximately from
6 to 8) of 0.038 using a hidrofilic catheter of 4 or 5F. Of the total of the 37
cases, we obtained correctly embolization in 33 patients (89.2%), being necessary
a reembolization in three cases (10.8%) of which one finished in surgery. Only in
a case (2.7%) surgery was practised for embolization incomplete.
PMID- 23155654
TI - [Urethral polyposis in adolescence].
AB - Polyps in the urinary tract are a rare entity in infants and children. The most
frequent location when they appear is the ureter. These benign lesions with no
malignant potential have a varied form of presentation and in most cases must be
distinguished from malignancy. The suspected diagnosis is due to urinary
obstruction; nevertheless radiological evidence played a key role in the final
diagnosis. The management is as less invasive as possible, with endoscopy
resection or minimally invasive surgery.
PMID- 23155655
TI - [Crossed testicular ectopia in indigenous child].
AB - The crossed testicular ectopia is an extremely rare entity, characterized by
migration of both testicles in the same inguinal canal, often associated with
symptomatic inguinal hernia and cryptorchidism in the contralateral side. About
one hundred cases have been published in the literature. We report a case of
crossed testicular ectopia in brazilian indigenous boy, aged two years old, with
a favorable post operative.
PMID- 23155656
TI - [Management of penile trauma from compressed air gun in a child].
AB - We report on a 6-year old child with a penile injury resulting in the inclusion
of a pellet in the cavernous body, by a fortuitous shot. Conservative approach
with elective extraction of the bullet and cavernous body repair led to a
satisfactory result, in better anatomic conditions. The patient did not have any
perioperative complication. Accidents by air weapons are particularly important
in children, because these weapons are erroneously considered as toys. Air gun
injuries to head, neck and thorax have been often published, but these injuries
are rare in the chidren genitourinary area.
PMID- 23155657
TI - [Surgical closure of ductus arteriosus in the extreme or very extreme preterm
infant].
AB - OBJECTIVES: The surgical close of patent ductus arteriosus in the extreme or very
extreme premature presents difficulties, because of its anaesthesia, surgical
intervention and the clinical circumstances that usually accompany this
pathology. We reviewed our experience in order to understand the factors that
have contributed to the obtained results. METHODS: In all the reviewed patients
we evalue: gestational age, birth weight, drug treatment, surgical close,
incidence of bronchopulmonary dysplasia, necrotizing enterocolitis and renal
failure, time of hospitalization, mortality and its causes. RESULTS: The sample
is constituted of 26 prematures whose average gestational age is 26.24 weeks and
average weight 885 g. 22 were treated with indomethacin, at an average age of 7
days, and all of them underwent surgical close, at an average age of 19 days (0
50). 10 patients suffered bronchopulmonary dysplasia, operated when they were 28
days of life. 7 suffered renal failure, 5 of them after drug treatment. 6
suffered necrotizing enterocolitis. 7 died (27%), 3 of them because of
prematurity and preoperative severe pathology, 2 because of heart disease, and 2
because of severe necrotizing enterocolitis. CONCLUSIONS: Surgical ligation of
patent ductus arteriosus in these patients is well tolerated, especially if the
attention to prevent bronchopulmonary dysplasia, necrotizing enterocolitis and
renal failure is optimized. Mortality in our series is not very different from
that provided for the total of prematures with similar gestational age and birth
weight, regardless of their pathology.
PMID- 23155658
TI - [Results of living donor kidney transplant in pediatric recipients, with graft
obtained by laparoscopy].
AB - OBJECTIVE: Analyze the results of the living related donor kidney transplant
(LRDKT) in our center. PATIENTS AND METHODS: Between December 2005 and 2008, 34
kidney transplants in pediatric recipients were performed in our center, 7
(20.58%) of which were LRDKT with grafts obtained via laparoscopy. The donor was
the mother in 4 cases and the father in 3. Mean age of the donors was 43 years
(38-48) and of the recipients 12.5 years (9-17). Four were a first transplant
(one of them planned) and three retransplantations. RESULTS: Cold ischemia time
was < 2 hours in every case while warm ischemia did not show significant
differences with the cadaveric donor transplant. None had initial graft
dysfunction. No vascular complications occurred, but there was a urinary fistula
secondary to ureteral necrosis, resolved with a new reimplantation. Survival of
the patient and graft is 100%, superior to that of the cadaveric grafts within
the same period. Current mean plasma creatinine is 0.8 mg/dl (0.7-1.39) and mean
creatinine clearance is 80 cc/min/1.73 m2 (75-90). No donor had surgical
complication and all maintain good kidney function. CONCLUSIONS: The short term
results of the LRDKT with grafts obtained by laparoscopy in our center are
similar to those described by groups with large experience, which makes it
possible to continue offering it with guarantee.
PMID- 23155659
TI - [Ten years of laparoscope hernia repairs. Indications and results].
AB - INTRODUCTION: The inguinal hernia surgery is common in the pediatric population
although laparoscopic management today, is not considered the standard technique.
The aim of this study is to review the results of our study and evaluate the
contralateral side in patients with unilateral hernia. MATERIAL AND METHODS:
Retrospective study of laparoscopic herniorraphy at our hospital since the
beginning of the art in 1999 with a total of 348 patients. The indications of
laparoscopy have been the availability of umbilical hernia associated, doubt
diagnosis, recurrence of open surgery, bilateral tumor and casual diagnosis. We
analyzed the following parameters: sex, age, weight, associated diagnosis, intra
and postoperative complications, recurrence and follow-up. RESULTS: 474 hernias
were repaired laparoscopically in 348 patients. A predominance of males against
females (30%). In 37 patients (11%) the diagnosis was made during another
operation. 39 patients with recidive open surgery were operated by laparoscopy.
We had only 2% intraoperative complications and 2% of recurrences. The follow-up
period is 10 years. CONCLUSIONS: Laparoscopic herniorraphy may be a routine
procedure with results comparable to open surgery. Laparoscopy offers a good
overview of the anatomy, easily identifying the defect, with a technique
increasingly used in the field of pediatric surgery.
PMID- 23155660
TI - [Cervical cystic lymphangioma: still a challenge].
AB - INTRODUCTION: Cervical lymphangiomas can not only cause severe sequelae
(aesthetic, phonatory or deglutory) but can also be life thereatening due to
airway compresion or massive bleeding. This paper analyzes our surgical results,
the value of prenatal diagnosis and the use of new techniques such as the EXIT
procedure for airway control in sereve cases. PATIENTS AND METHODS: We
retrospectively reviewed the medical record of patients with cervical
lymphangiomas treated in our center between 1986 and 2009, according to our
Clinical Documentation Database. Data referred to prenatal diagnosis, intrapartum
airway management, surgical procedures and morbidity, sclerosing substance
infiltration and long term sequelae was analyzed. RESULTS: Thirteen cases were
identified. 53.8% of the patients were diagnosed by prenatal ultrasound, and MRI
was performed in 46.1%. The tongue was affected in 30.7%, parotid glands in 38.4%
and airway in 38.4%. Four EXIT procedures were carried out (nasotracheal
intubation) and one emergency tracheotomy was needed. Five patients required more
than one surgical prodedures, including partial glossectomy, with severe
intraoperatory complications in 23% (bleeding, pharyngeal damage). In eight
patients primary or adyuvant sclerotherapy was used. Three children with giant
masses died, two due to intracystic bleeding and one from sepsis. Among the
survivors, 50% have no sequelae. CONCLUSIONS: Cervical lymphangiomas are a very
sereve condition, not only due to possible airway compresion or massive bleeding
but also becose of the severe secualaes they may cause. Tongue or parotid gland
infiltration are difficult to treat. In severe cases diagnosed prenatally a close
follow up in selected centers, with multidisciplinary teams consisting of
obstetricians and pediatric surgeons, trained in the EXIT procedure is warranted.
Despite therapeutic efforts the prognosis of large masses is still poor.
PMID- 23155661
TI - [Evaluation of the long-term results of surgical treatment of palmar
hyperhidrosis].
AB - INTRODUCTION: Palmar hyperhidrosis (PH) is a relative frequent pathology which
basically affects patients' life quality limiting social and laboral life. The
treatment of choice is thoracoscopic sympathectomy, most frequently done during
adulthood. The aim of our study was to evaluate the degree of satisfaction of the
pediatric patients treated in our centre. MATERIAL AND METHODS: We
retrospectively reviewed the clinical records of the patients controlled and
treated in our centre during the last 4 years evaluating the symptoms before
surgery, the level of the sympathectomy and postoperative complications. To
evaluate the long-term results we developed a telephone questionnaire for all the
patients centralized on the grade of satisfaction, the efficiency of the
treatment, the compensatory sweating and the observed changes in life quality.
The medium follow-up time was 26.5 months (rango 6 months to 4 years). RESULTS:
In total 6 patients were reviewed (4 female, 2 male), medium age 12, 8 years
(rango 8 to 18 years). Thoracoscopic sympathectomy was done at the level of T2 or
T3 associating T4 in 1 case. We just observed 1 postoperative complication which
consisted in a disestesia of the upper extremity and which disappeared
spontaneously without sequels. Patients referred total relief of palmar sweating.
Only 1 case reported residual sweating unilaterally in the tenar region, but in
all of them sweating of feet still persisted (3 of low grade and 3 of moderate
grade). In 50% of the cases we observed compensatory sweating localized at the
back of moderate grade in 2 patients and at the upper legs of more severe grade
in 1 of them. Only this last patient reported that the compensatory sweating
affected his everyday life. We also observed that the patients where the
sympathectomy had affected more than 1 ganglia (T2+T3; T3+T4; T2+T3+T4) referred
a higher grade of compensatory sweating. All the cases reported an important
improvement in life quality, in the social as in the formative manner. They were
all very satisfied with the results of the surgery and none of them (neither the
children nor the parents) regretted the intervention. The cosmetic result of the
surgical scars was also satisfactory. CONCLUSIONS: The thoracoscopic
sympathectomy is an efficient procedure for the treatment of palmar
hyperhidrosis. Despite the compensatory sweating patients usually are very
satisfied with the results. Since palmar hyperhidrosis is not a pathology which
improves spontaneously and the surgical treatment has minimal complications we do
not think that the surgery should be postponed in pediatric patients.
PMID- 23155662
TI - [Treatment of chronic ischial ulcer in the pediatric patient refractory to
conventional treatments].
AB - BACKGROUND: Pressure ulcers are an emerging disease, due to survival increase of
pediatric patients at risk (myelomeningocele, infantile cerebral paralysis,
paraplegic, prematures with neurological sequelae, etc.), including as well, long
time staging patients at intensive care units. OBJECTIVES: Provide for long-term
treatment to pressure ulcer refractory to debridement procedures. METHODS: We
used the biceps femoris muscular flap technique associated with fasciocutaneous
flap in two patients, 16 year-olded, with tetraparesis secondary to cerebral
palsy and, another 18 year-olded, with myelomeningocele sequelae. Both had
sciatic ulcers refractory to treatment, 2 and 3 years evolutioned, respectively.
RESULTS: The outcome was excellent in both cases, with definitive healing of the
ulcer and no recurrence during one and two month follow-up. CONCLUSIONS: This
technique, used in adults, can be applied to pediatric patients if no possibility
of wandering. Muscle acts as a cuff between bone and skin and provides coating to
the zone suffering pressure as an hypervascularized and no-functioning for active
movement structure, but feasible in terms of trophism.
PMID- 23155663
TI - [Indication for early excision of the giant congenital nevus].
AB - INTRODUCTION: Most of specialists involved in giant congenital nevi (GCN) care,
agree that the risk of melanoma is probably not significant enough to warrant the
prophylactic removal of all those lesions. However, many patients benefit from
very early surgical procedures. MATERIAL AND METHODS: In the last 15 years 41
children undergwent surgical removal of their large or giant melanocityc lesions
in the first year of life at our institution. Indications for such an early
excision were as follows: painful ulceration or bleeding, alarming dermatoscopic
changes, location in the scalp being removable with primary closure, concomitant
surgical procedures, multiple expected interventions and severe parental
psychosocial distress. RESULTS: All patients had a good cosmetic result. All
nevus in the scalp between 3 and 5 cms were removed with a primary closure in
order to avoid future need of scalp expansion. Familial psychological distress
improved significantly and disturbances related to scholar activities were not
noticed. CONCLUSIONS: Despite the lack of international consensus regarding the
appropriate timing for large or giant congenital nevi excision, a selection of
patients and their families can benefit from early surgical removal.
PMID- 23155664
TI - [Results of the use of laparoscopic anti-reflux procedure for the prevention of
episodes of apnea, bradycardia and desaturation].
AB - In 1986 the National Institutes of Health Consensus Developement Conference on
Infantile Apnea and Home Monitoring defined the Apparent Life Threatening Events
(ALTEs) as those frightening episodes for the observer which are determined by a
combination of apnea (central or obstructive), changes in colour (cianosis,
congestive pallor) and marked changes in muscular tone, asphyxia. Despite the
fact that its cause still remains unknown, many centres relate ALTE with
gastroesophageal reflux disease (GERD) and therefore recommend medical treatment
of GERD to those patients with ALTE. However there are very few articles that
proof the efficacy of surgical treatment in patients with ALTE and GERD. We
carried out a retrospcective review between 2000 and 2008 of those patients with
ALTE who underwent a laparoscopic antirreflux procedure. The study included the
realization of contrast x-ray, pHmetry and laryngeal, digestive and bronchial
endoscopy. During this period antirreflux (with either Nissen or D'Or technique)
procedure was carried out by laparoscopic approach in the patients with ALTE and
GERD. Median of gestational age was 32 week, mean birth weight was 1800 g, mean
age at the time pof surgery was 217 days (range 32-410). All these patients had
previously presented 3 or more events of ALTE and had been treated medically for
GERD. pHmetric studies were no conclusive, In 6 out of 15 patients had different
grades of arithemoid oedema. All the patients presented gastroesophageal reflux
(grades II-III) in the constrast x-ray. Mean follow up was 1258 days. 7 from 8
patients presented clear improvement. Morbimortality derived from surgery was
null.
PMID- 23155665
TI - [The fetal ultrasonography in the second quarter: interest for the pediatric
surgeon].
AB - INTRODUCTION: The paediatric surgeon should know the details of prenatal
ultrasound diagnosis to participate in advising parents about the continuation of
the pregnancy, and to plan the prenatal and postnatal treatment. Our objectives
are: to determine the incidence of congenital anomalies detected with ultrasound
in the 2nd trimester, the number of these diagnoses which is confirmed at birth
and what is the usefulness of this test when advising parents. PATIENTS AND
METHODS: We reviewed the prenatal ultrasound in 2nd trimester reports made from
January 2005 to July 2009. We note the ultrasound findings, the maternal and
gestational age. The evolution of anomalies of the fetuses and the number of
spontaneous and volunteers abortions are noted. Finally, the diagnoses are
checked in the newborns. RESULTS: 10,256 ultrasonographies are made in this
period. 209 stories of pregnant women (2%), which present fetal pathology
amenable to general surgical treatment, are accessible for study. These include:
182 urologic disorders (85.44%), 13 digestive disorders (6.1%), 6 thoracic
disorders (2.8%), 6 multiple malformations (2.8%), 4 maxillofacial disorders
(1.88%) a sacrococcygeal teratoma (0.47%), an umbilical cord cyst (0.47%), 7
pregnancies are spontaneous abortion and 7 are terminated voluntarily. 183
stories of newborns are reviewed, we can confirm 48 uropathies (26.37%), 4
digestive malformations (30.77%), 4 thoracic disorders (66.66%), 2 maxillofacial
disorders (50%) and 1 teratoma. CONCLUSIONS: Ultrasonography in the 2nd trimester
detects almost 2% of specific fetal malformations. False positives are common in
all diagnostic groups. The number of abortions and the terminations of pregnancy
is low, most of them are polymalformated fetuses. We believe that ultrasonography
in the 20th week have low value to counsel the termination of pregnancy, because
only 7 of the 160 terminations indicated in our hospital during the study period,
correspond to fetuses with pathology detected in the 2nd trimester. We recognize
the usefulness of this test but, the false positive and favorable developments in
a high percentage of fetuses, make us to be cautious to advise the continuation
of pregnancy and the indication of treatment.
PMID- 23155666
TI - [Intestinal transplant: in what phase are we?].
AB - OBJECTIVE: To analyze the evolution of Small Bowel Transplantation program since
the beginning of the program. MATERIAL AND METHODS: [corrected] All children who
underwent intestinal transplantation between 1997 and 2009 were retrospectively
reviewed: epidemiological data, status before transplant, surgical technique,
immunosupression, results, survival and long.term quality of life were analysed.
RESULTS: Fifty-two intestinal transplants were performed in 46 children (20
isolated bowel, 20 combined liver and intestine, and 12 multivisceral); median
age was 32m (range 7m-19a); weight 12,3 kg (range 3,9-60); 31 had short gut
syndrome, 8 dismotility, 5 intractable diarrhea, and two were miscellaneous.
Intestinal adaptation was initially attempted in 26 patients, without success, 20
were directly listed for transplant. The modality of transplant was modified in
17 while listed. Baseline immunosupression consisted of tacrolimus and steroids,
although 5 required conversion to Sirolimus later. Six died during the first
month, due to sepsis/multiorganic failure (poor status at transplant); 13 died
during the long-term follow-up. Acute rejection was seen in 20, chronic rejection
in 3, PTLD in 8 (6 died) and GVHD in 5 patients (3 died). Overall survival after
5 years of follow-up is 65,2 % (51,7% for the graft). From 2006 to 2008, overall
patient/graft survival at 6 m, 1 and 3 years after transplant is 88,7/84,1,
81,2/81,2 and 81,2/71,1%, respectively. After a median follw-up of 39 +/- 29
months, 27 patients are alive (59%), off TPN, (70% had their ostomy taken down),
go to school, are scarcely hospitalized and enjoy a good quality of life.
CONCLUSIONS: Intestinal transplantation has consolided itself as a good choice
for irreversible intestinal failure, being feasible to achieve a normal life.
Although overall survival diminishes over time, the center experience has
improved the results. These patients need a very close follow-up, once transplant
is over, in order to get an early diagnose of immunological complications.
PMID- 23155667
TI - [Utility of the ECMO in patients with congenital diaphragmatic hernia].
AB - At the moment the extracorporeal membrane oxygenation (ECMO) constitutes the last
link in the therapeutic one of the handling of the respiratory failure in
patients with Congenital Diaphragmatic Hernia (HDC). We presented our experience.
From January 2001 we arrange the ECMO in neonative UCI. 76 HDC, 13 (3 rights and
10 lefts) they have needed ECMO (one in two occasions; altogether 14 procedures).
Criteria of inclusion: refractory hypoxaemia, oxigenaction index > 40 and weight
> 2 kg. 5 girls and 8 boys with gestacional age between 35 and 41 weeks (average:
38) and weight when being born between 2,300 and 3,500 grams (average 2,817). In
6 cases (5 transferred from other centers) the diagnosis was posnatal. Of the 7
with prenatal diagnosis, in 4 cases fetal therapy by means of traqueal occlusion
had been made. Veno-venous in 8 and veno-arterial procedure in 5. Rank of
duration: 68-606 hours, average of 228.35. The surgery has been made before the
ECMO in 9 cases, 2 during and 1 later. In an occasion there was no surgery. The
complications have been of hemorragico type in one patient and infectious in
three cases with sudden sepsis in one. Precocious mortality has been of 6
patients and delayed the 2 (total 61%). Although this procedure has the high
morbi-mortality, it is necessary to consider that is patients very badly
prognosis without another alternative (with mortality of the 100%). Multicentric
studies are needed to establish indicators prognoses pre and postbirthdays.
PMID- 23155668
TI - [Percutaneous gastrostomy: when should antireflux surgery be associated?].
AB - INTRODUCTION: Percutaneus gastrostomy placement is a procedure widely performed
in children with failure to thrive or intolerance to oral feeding. At the moment
of making the indication, the need of an antir-reflux surgery in the same
procedure comes to question. The aim of this study was to analyse which
preoperative factors are associated with a higher risk of a posterior
fundoplication. MATERIAL AND METHODS: We realized a retrospective review of 67
patients divided in 2 groups (cases and controls) in which a percutaneus
gastrostomy (PEG) had been made by our service in the period of 1997 to 2008. We
compared these two groups: Group A (n=11) - patients with severe gastroesophageal
reflux who required a Nissen procedure afterwards; Group B (n=56) - patients who
kept without reflux after PEG. We analyzed the different preoperative factors
that could have been in association to severe reflux after gastrostomy. RESULTS:
Mean age at the moment of undergoing PEG was 15 months. Mean time of follow up
was 3,5 years. Only neurological impairment and documented reflux pregastrostomy
were associated with the need of an antirreflux surgery after PEG. CONCLUSIONS:
Neurological impairment and documented pregastrosotmy GER could be an indication
of concurrent antirreflux surgery at the time of gastrostomy.
PMID- 23155669
TI - [Scarring after Mustarde otoplasty: importance of cures and post-operative follow
up of the patients].
AB - INTRODUCTION: In the treatment protocol for patients with Mustarde otoplasties we
use tennis head sweatbands for 2 months (to be worn all the time in the first
month and only at night in the second month) to protect the correction obtained
and to avoid traumatisms. MATERIAL AND METHODS: We describe the cases of 3
patients who underwent Mustarde otoplasty and presented sloughs in the anterior
edge of the antehelix that are secondary to the pressure of the compression
bandage. RESULTS: One patient operated for unilateral malformation suffered
bilateral scars (in the operated ear and in the healthy one). This prove that the
scars are secondary to the dressings not to surgery. In two patients the sloughs
evolved into the formation of nodular hypertrophic scars, which were slowly
corrected with silicone dressings and externally applied corticosteroids and
moisturising creams in one patient and had to be resected in the other.
CONCLUSIONS: It is important to give a detailed explanation to the parents about
the mission and characteristics of the sweatbands, and also about the need to
frequently check their correct placing. This is to avoid a complication that,
without spoiling the final result of the otoplasty, reduces patient satisfaction
and extends the recovery period.
PMID- 23155670
TI - A clinican's guide to adult attention-deficit hyperactivity disorder.
AB - While attention-deficit hyperactivity disorder (ADHD) has been traditionally
viewed as a childhood ailment, longitudinal data suggest that it persists into
adulthood for most affected individuals. Adult ADHD is now recognized as a
legitimate diagnosis with clinical and epidemiological implications. It is
estimated that 4% of American adults are afflicted by this disorder. There have
been advances in adultADHD screening tools, diagnostic guidelines, medication
delivery systems and psychosocial treatments. Despite these gains, there is great
variability among clinicians in the diagnosis and treatment of adult ADHD. This
article reviews controversies surrounding the diagnosis and treatment of adult
ADHD and suggests strategies to overcome existing obstacles.
PMID- 23155671
TI - Mental-health conditions, barriers to care, and productivity loss among officers
in an urban police department.
AB - BACKGROUND: Police officers are frequently exposed to situations that can
negatively impact their mental health. METHODS: We conducted this study of an
urban police department to determine 1) the prevalence of post-traumatic stress
disorder (PTSD), depression, and alcohol abuse; 2) patterns of and barriers to
mental-health services utilization; and 3) the impact these conditions have on
productivity loss. RESULTS: Among 150 officers, PTSD (24%), depression (9%), and
alcohol abuse (19%) were common. Only46.7% had ever sought mental-health
services; the most commonly cited barriers to accessing serviceswere concerns
regarding confidentiality and the potential"negative career impact." Officers
with mental-health conditions had higher productivity loss (5.9% vs 3.4%,
P<0.001) at an annual cost of $4,489 per officer. CONCLUSION: Mental-health
conditions among police officers are common, and costly, yet most officers had
never accessed mental-health services; many due to modifiable risk factors.
PMID- 23155673
TI - Distal embolization from Mynx device.
AB - Vascular closure devices are commonly used to obtain arterial access site closure
after cardiovascular procedures. They are popular as they decrease time to
hemostasis and ambulation while improving patient comfort by eliminating need for
compression. However, complications due to vascular closure devices are not
uncommon. We report a case of possible intravascular distal embolization of water
soluble PEG polymer that is deployed extravascular using the Mynx vascular
closure device.
PMID- 23155672
TI - Ocular manifestations of systemic inflammatory diseases.
AB - Inflammation of the eye is often times seen in association with systemic
inflammatory diseases. Understanding the various forms of ocular involvement in
these conditions is important as untreated ophthalmic involvement can lead to
severe vision loss. In addition to providing a basic framework for diagnosis and
treatment, this review will highlight the ocular manifestations of the following
systemic inflammatory conditions: rheumatoid arthritis, systemic lupus
erythematosus, Wegener's granulomatosis, Sjogren's syndrome, polyarteritisnodosa,
primary antiphospholipid syndrome, Behcet's syndrome, Kawasaki disease, Cogan's
syndrome and relapsing polychondritis.
PMID- 23155674
TI - Anaphylactic reactions with intravenous vitamin K: lessons from the bedside.
AB - Vitamin K is used as a correction factor to avert the risk of bleeding due to
warfarin overdose. Among the reported complications of this therapy, the most
serious one is the anaphylactic cardiovascular collapse caused by intravenous
infusion of the drug. We report herein a patient with over-anticoagulation from
warfarin use and a subcapsular renal bleeding who developed a fatal anaphylactic
shock after vitamin K administration via slow intravenous infusion. Vigilance
with the intravenous formulation of this agent should always be sought in order
to prevent fatal outcomes, especially in patients with severe comorbidities.
PMID- 23155675
TI - A 26-year-old lady with unexplained ascites: an intriguing diagnosis.
PMID- 23155676
TI - Typhus syncopalis: an epidemic in Connecticut in 1823.
AB - In 1825 Dr. Thomas Miner wrote about an epidemic that occurred in Middletown,
Connecticut in 1823. He called this disease "Typhus syncopalis," sinking typhus,
or New England spotted fever. Differences in the understanding of disease
processes in the early 19th century preclude a definitive modern equivalent
fortyphus syncopalis. In addition, there are disagreements among Dr. Miners'
contemporaries with regard to fever classification systems. Examination of the
symptoms and physical findings as described by Dr. Miner suggest the presence of
encephalitis or meningitis as well as a syndrome resembling a shock-like state.
Based on symptom comparisons, this paper suggests that typhus syncopalis was
likely meningococcemia caused by Neisseria meningiditis.
PMID- 23155677
TI - The president's page. 1962.
PMID- 23155678
TI - Assisted dying.
PMID- 23155680
TI - Mentors and mentoring.
PMID- 23155679
TI - Living in the future.
PMID- 23155681
TI - Turning words into action.
PMID- 23155682
TI - Obesity, adolescence, and sleep deprivation.
PMID- 23155683
TI - 18F-DOPA positron emission tomography/computed tomography application in
congenital hyperinsulinism.
AB - Congenital hyperinsulinism (CHI) during infancy is characterized by inappropriate
insulin secretion resulting in persistent hypoglycemia. This can lead to
irreversible severe neurological damage in the infant. There are two main
histologic subtypes: diffuse and focal, both of which may require different
surgical strategies. It is very important to differentiate focal leisons from
diffuse leisons. However, the differentiation of diffuse leisons from focal
leisons is challenging. Affected pancreatic areas utilize dihydroxyphenylalanine
(DOPA) at a higher rate than normal pancreatic tissues; thus, labeling of L-DOPA
with fluorine-18 (18F-DOPA) allows functional mapping of hyperinsulinism using
positron emission tomography/computed tomography (PET/CT). In this article, we
reviewed the 18F-DOPA PET/CT application in CHI. The aim of this review is to
enhance the recognition of 18F-DOPA PET/CT application in the diagnosis of CHI.
PMID- 23155684
TI - Pathogenesis of propylthiouracil-related hepatotoxicity in children: present
concepts.
AB - Propylthiouracil (PTU), carbimazole (CMZ) and methimazole (MMI) are the most
common drugs used today in cases of adolescent thyrotoxicosis. Skepticism has
been growing regarding the use of PTU in childhood and its association with
severe liver failure. The aim of this review is to present all the recent data
regarding pathogenesis of PTU hepatotoxicity in children and adolescents.
Specifically, reactive drug metabolites and increased oxidative stress can
directly activate inflammatory and immunological pathways. Drugs are not only
immunogenic because of their chemical reactivity but also because they may bind
through electrostatic forces to available T-cell receptors. Redox modulation is
also a key regulatory strategy in the adaptive immune system. Subtle changes in
the extracellular redox status may cause profound functional changes in redox
sensitive proteins. Genetic factors that affect drug biotransformation could also
be implicated in this mechanistic model of PTU-related hepatotoxicity. Further
studies are needed to fully understand the pathophysiology of PTU-induced liver
damage.
PMID- 23155685
TI - Adhesion of the labia minora in girls: a common disorder that is rarely
considered.
PMID- 23155686
TI - Thyroid nodules in children and adolescents: a single institution's experience.
AB - OBJECTIVE: The aims of this study were to analyze the role of fine-needle
aspiration biopsy (FNAB) in the management of pediatric thyroid nodules and to
analyze the malignancy risk of thyroid nodules by studying the association
between autoimmune thyroiditis and thyroid cancer. METHODS: We conducted a
retrospective study on 111 patients with thyroid nodules diagnosed in childhood
or adolescence. FNAB was performed in 46 participants with thyroid nodules after
ultrasonography (US). Cytology diagnoses were categorized as insufficient,
benign, suspicious, and malignant. Clinical and surgical follow-up data were
obtained from medical records. The clinical correlation and accuracy of FNABs
were evaluated. RESULTS: The family history was positive in four patients. Forty
six patients had positive antithyroid antibodies and an inhomogeneous
hypoechogenic US pattern. One patient had previous neck irradiation history.
Eighty-six patients (%77.5) were euthyroid. All patients underwent US
examination. The FNAB results of the 46 patients were 29 (63%) benign cases, 7
(15%) insufficient, and 10 (22%) suspicious patients. Malignancy was not reported
at all. A repetition of FNAB in two benign cases, which were diagnosed with
papillary carcinoma during followup, reported these cases as suspicious. Ten
patients with suspicious FNAB results underwent surgery because of increases in
the size of the nodules; two patients were diagnosed with papillary carcinoma. In
this study, the prevalence of malignancy was 4.5% in patients with thyroid
nodules. CONCLUSION: In this study, the importance of FNAB in the diagnosis and
follow-up of thyroid nodules in childhood has been observed, and risk factors,
such as history of familial thyroid carcinoma, radiotherapy to the neck at
younger ages, suspicious cytological findings, and increased nodular sizes during
follow-up in cases with Hashimoto thyroiditis have been correlated with increased
thyroid carcinoma malignancy risk.
PMID- 23155687
TI - Effects of selenium supplementation in the early stage of autoimmune thyroiditis
in childhood: an open-label pilot study.
AB - AIM: The aim of the study was to evaluate the role of selenium (Se) in childhood
autoimmune thyroiditis regarding its effect on thyroid-stimulating hormone (TSH),
free thyroxine (fT4), thyroid peroxidase antibodies (TPOAb), thyroglobulin
antibody (TgAb), and thyroid morphology. METHODS: Newly diagnosed 23 euthyroid
children (mean age, 12.3 +/- 2.4 years) with Hashimoto thyroiditis (HT) received
only 50 microg L-selenomethionine per day for 3 months. The baseline basal
urinary iodine level, serum Se, TSH, fT4, TPOAb, and TgAb concentrations, and
thyroid morphology by ultrasound were detected. We reanalyzed the TPOAb and TgAb
changes at the 3rd month and then compared the thyroid morphology with 30 healthy
individuals (mean age, 12.1 +/- 2.1 years) at the 6th month. RESULTS: Serum
TPOAb, TgAb, and thyroid echogenicity were unchanged with Se supplementation. A
prominent decrease in thyroid volume was noteworthy; 35% of patients showed a
thyroid volume regression rate of > or = 30%. CONCLUSION: In terms of TPOAb and
TgAb, Se may not benefit in the euthyroid period of HT, but Se supplementation
seems to lead a favorable response in thyroid volume regression.
PMID- 23155688
TI - Overestimation of final height prediction in patients with classical congenital
adrenal hyperplasia using the Bayley and Pinneau method.
AB - BACKGROUND: A typical growth pattern with decreased pubertal growth spurt has
been identified in patients with classical congenital adrenal hyperplasia (CAH).
OBJECTIVE: To evaluate the accuracy of final height predictions in patients with
CAH using the Bayley and Pinneau (B&P) method. PATIENTS AND METHODS: Using growth
and final height data of 92 patients (57 F/35 M) with CAH due to 21-hydroxylase
deficiency (38 SV/54 SW), final height predictions with the B&P method were
compared to actual final heights. RESULTS: In females, mean final height was
159.9 +/- 5.3 cm (-1.0 +/- 0.7 SDS) compared to predicted mean final height of
167.9 +/- 10.7 cm (+0.5 +/- 1.7 SDS), p < 0.001, overestimation 7.3 +/- 9.5 cm.
In males, mean final height was 170.1 +/- 6 cm (-1.2 +/- 0.8 SDS) compared to
predicted mean final height of 185.6 +/- 13.4 cm (+1.2 +/- 1.9 SDS), p < 0.001,
overestimation 13.9 +/- 10.8 cm. CONCLUSION: In classical CAH, final height
prediction using the B&P method results in significant overestimation of final
height.
PMID- 23155689
TI - Is the growth outcome of children with idiopathic short stature and isolated
growth hormone deficiency following treatment with growth hormone and a
luteinizing hormone-releasing hormone agonist superior to that obtained by GH
alone?
AB - AIM: The aim of this study was to evaluate the effect of combined therapy with
growth hormone (GH) and luteinizing hormone-releasing hormone agonist (LHRHa) on
the near-final height (NFH) of children with idiopathic short stature (ISS) and
growth hormone deficiency (GHD) in early puberty. METHODS: A retrospective
analysis of 20 patients with ISS and 9 patients with GHD treated with combined
therapy was undertaken. Twelve children with ISS and ten with GHD, treated with
GH alone, served as controls. Patients were matched at baseline for chronological
age, bone age, height standard deviation score (SDS), and pubertal development.
RESULTS: Patients with ISS or GHD treated with combined therapy improved both
their predicted adult height (PAH) at 2 years of therapy (ISS, p < 0.001; GHD, p
= 0.03) and their NFH (ISS, p < 0.05; GHD, p = 0.05). Treatment with combined
therapy did not generate additional benefits on the PAH after 2 years of therapy
(ISS children, an increase of 7.9 +/- 4.9 cm with combined therapy vs. 7.3 +/-
6.0 cm with GH; GHD children, an increase of 6.8 +/- 7.8 cm with combined therapy
vs. 5 +/- 5.9 cm with GH). The total height gain SDS was higher in patients
treated with GH alone compared with those with combined therapy, but the
difference was not significant (ISS children, a gain of 2.4 SDS with GH vs. 0.8
SDS with combined therapy; GHD children, a gain of 1.8 SDS with GH vs. 0.6 SDS
with combined therapy). CONCLUSIONS: Although 2 years of combined treatment with
GH and LHRHa improved the PAH and the NFH of ISS and GHD patients in early
puberty, this improvement was not significant compared with that observed in
similar subjects treated with GH alone.
PMID- 23155690
TI - Molecular defects of the GnRH-receptor gene in Chinese patients with idiopathic
hypogonadotropic hypogonadism and the severity of hypogonadism.
AB - BACKGROUND: Human mutations in the gonadotropin-releasing hormone receptor
(GnRHR) gene cause normosmic idiopathic hypogonadotropic hypogonadism (IHH). At
least 19 different mutations have been identified in this G-protein-coupled
receptor, which consist mostly of missense mutations. OBJECTIVES: To identify and
determine the frequency of mutations in the coding region of the gonadotropin
releasing hormone receptor (GnRHR) gene in forty Chinese patients with normosmic
idiopathic hypogonadotropic hypogonadism (IHH) and establish genotype/phenotype
correlations where possible. METHODS: The diagnosis of HH was based on absent or
incomplete sexual development after 17 years of age in girls and 18 years in boys
associated with low or normal levels of LH in both sexes and low levels of
testosterone in males and of estradiol in females. All patients presented with a
normal sense of smell in an olfactory specific test. Forty IHH patients and 40
controls were screened for mutations in the coding sequence of the GnRHR gene.
The coding region of the GnRHR gene was amplified by PCR and directly sequenced.
RESULTS: A missense mutation, serine 168 arginine (S168R), located in the fourth
transmembrane domain of the GnRHR gene, was identified as being in a homozygous
state in one male with complete HH. The S168R mutation has been previously shown
to be a cause in the complete loss of receptor function because hormone binding
to the receptor is completely impaired. In another patient, a compound
heterozygous mutation (Gln106Arg and Arg262Gln) was identified in a male with
partial HH. The Gln106Arg mutation is located in the first extracellular loop of
GnRH-R, this mutation decreases but not does eliminate GnRH binding; while
Arg262Gln mutation is located in the third extracellular loop of GnRH-R and only
decreases signal transduction. A good correlation between genotype and phenotype
was found in our patients. The patient, who was homozygous for the completely
inactivating S168R mutation, had complete HH. In addition, the affected patient
who was compound heterozygous for the Glnl06Arg--Arg262Gln mutations - has
partial HH. CONCLUSIONS: GnRHR mutations can be classified into partial or
complete loss of function mutations. Partially inactivating substitutions of the
GnRHR frequently found in familial hypogonadotrophic hypogonadism are Q106R and
R262Q. Comparison of compound heterozygous with homozygous patients suggests that
their phenotype and the response to GnRH is determined by the GnRHR variant with
the less severe loss of function.
PMID- 23155691
TI - Association of vitamin D receptor gene Cdx2 polymorphism with bone markers in
Turner syndrome patients.
AB - BACKGROUND: Turner syndrome (TS) patients usually have low bone mineral density
(BMD) and increased risk of osteoporotic fractures. We have previously
demonstrated an association of bb (BsmI polymorphic site) and ff (FokI
polymorphic site) vitamin D receptor (VDR) genotypes with reduced BMD in TS
patients. AIM: To analyze the relationship between VDR-Cdx2 polymorphism and BMD
as well as bone metabolic variables in TS patients. METHODS: Fifty-five TS
patients and 59 control women were studied. VDR-Cdx2 genotypes were determined
using TaqMan probes in a real time thermocycler. Lumbar and femoral BMD were
determined by dual-energy X-ray absorptiometry (DEXA) and serum intact
parathyroid hormone, osteocalcin and beta3-CrossLaps were determined by
electrochemiluminescence. RESULTS: Patients with genotype GG had higher levels of
both osteocalcin and beta-CrossLaps as compared to patients with genotype GA (p <
0.01 and p < 0.05, respectively). CONCLUSION: Patients carrying genotype GG have
higher levels of bone formation and resorption markers. This indicates a more
active bone turnover that could impact on their future bone mineral density.
PMID- 23155692
TI - Serum 25-hydroxyvitamin D levels do not correlate with asthma severity in a case
controlled study of children and adolescents.
AB - BACKGROUND: There is no consensus on the association between vitamin D and
asthma. OBJECTIVE: To determine the relationship between 25-hydroxyvitamin D
[25(OH)D] levels and asthma symptom severity in children and adolescents.
METHODS: A retrospective, case-control study of 263 subjects of ages 2-19 years
with asthma who were compared to 284 non-asthmatic controls of similar ages.
Subjects were excluded if they had diseases of calcium or vitamin D metabolism or
were receiving calcium or vitamin D supplementation. Serum 25(OH)D was measured
in all subjects. Asthma symptom severity, usually stratified into 6 steps, was
stratified into five steps [1-5] based on the number and dose of controller
medications used as outlined by the National Heart, Lung, and Blood Institute's
guidelines. Mean 25(OH)D values were compared between the asthmatic patients and
controls, as well as among the five steps of asthma symptom severity. Results
were adjusted for age, sex, BMI, race and severity of asthma symptoms. RESULTS:
There was no difference in 25(OH)D between asthmatic patients and controls (28.64
+/- 10.09 vs. 28.42 +/- 11.47, p = 1.0). However, there was a significant
difference in 25(OH)D between obese and non-obese asthmatic patients (23.33 +/-
7.67 vs. 30.16 +/- 10.20, p < 0.0001), as well as obese and non-obese controls
(24.56 +/- 9.90 vs. 29.50 +/- 11.66, p = 0.003). Mean 25(OH)D levels did not vary
significantly among the five steps of asthma symptom severity. CONCLUSIONS: There
were no differences in mean 25(OH) D levels between asthmatic patients and
controls. Mean 25(OH)D level was significantly lower in both the obese asthmatic
patients and obese controls. Asthma severity had no relationship to mean 25(OH)D
levels.
PMID- 23155693
TI - Assessment of the 21-hydroxylase deficiency and the adrenal functions in young
females with Turner syndrome.
AB - There are few reports of an association between Turner syndrome (TS) and 21
hydroxylase deficiency. However, this association is more frequent in some
populations. The aim of this study was to evaluate the incidence of 21
hydroxylase deficiency in patients with TS in our population. 21-hydroxylase
deficiency was evaluated in 44 TS cases with 45X (n=20) and 24 mosaic cases. A
standard dose adrenocorticotropic (ACTH) stimulation test (Synacthen, Novartis,
Basel, Switzerland) was performed, and 17 hydroxyprogesterone (17OHP),
dehydroepiandrosterone sulfate (DHEAS) and cortisol responses were evaluated.
Patients with increased 17OHP responses in the stimulation test also underwent 21
hydroxylase gene analysis. The mean age was 14.6 +/- 4 (2.6-22.4); 37 patients
were on growth hormone (GH) treatment. Nine patients were at prepubertal stage,
whereas 35 were pubertal (24 on gonadal steroids and 11 spontaneously). Six
patients were obese. Only one of our patients had a level of 7.5 ng/mL of 17OHP,
and there was no mutation found in congenital adrenal hyperplasia (CAH) genetic
analysis. In other cases, peak 17OHP levels were < or = 6 ng/mL. The mean peak
17OHP was 2.62 +/- 1.48 (1.19-7.5) ng/mL, the cortisol level was 37.6 +/- 8.43
(23.9-56.2) microg/dL and the DHEAS was 135.2+/- 87.3 (15-413) microg/dL. The
increased mean basal and peak cortisol levels (20.5 +/- 10.2 and 37.6 +/- 8.4
microg/dL) were remarkable findings. Whereas basal cortisol was above 20
microg/dL in 38.7% of patients, exaggerated results up to 56.2 microg/dL were
obtained in peak cortisol levels. The basal and peak 17OHP cortisol levels were
not correlated with the presence of puberty, chromosome structure, gonadal
steroid use, obesity or growth hormone use. This trial suggested that 21
hydroxylase deficiency was not common among patients with TS in our population.
Adrenal function should be assessed, at least in the presence of clitoral
enlargement in patients with TS, particularly if their karyotype does not contain
a Y chromosome.
PMID- 23155694
TI - The association of FGF23 levels in obese adolescents with insulin sensitivity.
AB - BACKGROUND: The fibroblast growth factor 23 (FGF23) is the most important
hormonal regulator of circulating phosphate levels. Apart from this essential
role, it may also act as a 'hormone-like' factor involved in glucose and lipid
metabolism. It is believed to have a potential role in the development of insulin
resistance. AIM: The aim of the study was to compare FGF23 levels between two
groups of obese adolescents: insulin resistant and non-insulin resistant.
PATIENTS: The study included 36 obese, insulin-resistant adolescents (21 boys and
15 girls) of pubertal age (mean age, 13.95 years; Tanner stage IV or V). The
control group consisted of 21 obese peers with normal HOMA-IR values. METHODS:
FGF23 levels were measured in a fasting blood sample by Human Intact FGF-23 ELISA
Kit (Immunotopics Inc., San Clemente, CA, USA). A standard oral glucose tolerance
test was performed, which assessed fasting and 120 min postload plasma glucose
and serum insulin levels; the insulin resistance index HOMA-IR was calculated.
The definition of insulin resistance was based on a HOMA-IR threshold set for
adolescents (> or = 3.16). RESULTS: There was a significant inverse correlation
between FGF23 levels and HOMA-IR (R = -0.26, p < 0.05) in the study group. FGF23
levels were also significantly lower in the study group (9.8 vs. 11.9 pg/mL, p =
0.026). CONCLUSIONS: In adolescents with simple obesity and insulin resistance,
FGF23 levels are lower compared with obese adolescents with normal HOMA-IR.
PMID- 23155696
TI - Metabolic impact of a ketogenic diet compared to a hypocaloric diet in obese
children and adolescents.
AB - BACKGROUND: The effects of carbohydrate-restricted (ketogenic) diets on metabolic
parameters in children have been incompletely assessed. OBJECTIVE: To compare the
efficacy and metabolic impact of ketogenic and hypocaloric diets in obese
children and adolescents. SUBJECTS: Fifty-eight obese subjects were placed on one
of the two diets for 6 months. METHODS: Anthropometric measurements, body
composition, oral glucose/insulin tolerance test, lipidemic profile, high
molecular weight (HMW) adiponectin, whole-body insulin sensitivity index (WBISI),
and homeostatic model assessment-insulin resistance (HOMA-IR) were determined
before and after each diet. RESULTS: Both groups significantly reduced their
weight, fat mass, waist circumference, fasting insulin, and HOMA-IR (p = 0.009
for ketogenic and p = 0.014 for hypocaloric), but the differences were greater in
the ketogenic group. Both groups increased WBISI significantly, but only the
ketogenic group increased HMW adiponectin significantly (p = 0.025). CONCLUSIONS:
The ketogenic diet revealed more pronounced improvements in weight loss and
metabolic parameters than the hypocaloric diet and may be a feasible and safe
alternative for children's weight loss.
PMID- 23155695
TI - Higher postprandial serum ghrelin among African-American girls before puberty.
AB - OBJECTIVE: Recent reports suggest that ghrelin regulation may differ by ethnicity
and age. This study was designed to examine circulating ghrelin among overweight
female African Americans across different age groups. METHODS: Eleven overweight
peripubertal girls, 17 overweight pubertal girls, and a control group of 18
overweight African-American premenopausal women ingested a standard liquid meal
after an overnight fast. Blood samples were obtained before the meal and for 4 h
postchallenge. Participants rated appetite by a visual analog scale. RESULTS:
Peripubertal girls demonstrated higher postprandial ghrelin and lesser ghrelin
suppression compared with adults (p < 0.05), corresponding with greater desire to
eat across the test period (p = 0.017). Fasting ghrelin tended to be inversely
related to fasting estradiol (r = -0.264, p = 0.076). CONCLUSION: Compared with
overweight African-American women, peripubertal girls had higher ghrelin as well
as greater appetite after a standard meal. These results may suggest a
dysregulation in ghrelin reflective of demands of growth.
PMID- 23155697
TI - The second report from Turkey: waist percentiles for 6-11-year-old children in
Elazig Province, Eastern Anatolia.
AB - OBJECTIVE: To construct waist percentiles for 6-11-year-old Turkish children in
Elazig Province, Eastern Anatolia. METHODS: This cross-sectional study was
performed with 3342 (1708 boys and 1634 girls) children from March to June 2007.
Waist circumferences (WC) were measured between the lowest rib and the superior
iliac crest, and centile curves were constructed with the Lambda-Mu-Sigma (LMS)
method. RESULTS: Towards 6-11 years, WC 50th percentile ranged from 57.54 to
67.04 cm in boys and 55.77 to 64.58 cm in girls. For both genders, WC increased
with age. At each age, boys had higher WC values than girls. For the entire
sample, mean WC was 62.5 +/- 6.8 cm for boys and 59.8 +/- 6.2 cm for girls.
Median WC was 62.0 cm (32.0-90.0) for boys and 59.0 cm (46.0-87.0) for girls.
CONCLUSIONS: The large differences in the values obtained worldwide emphasize the
necessity of providing population-specific WC reference curves from different
populations, which in turn may result in an international reference standard
similar to that provided for body mass index.
PMID- 23155698
TI - Association analysis between endothelial function related factors and coronary
artery stenosis degree in coronary heart disease patients with type 2 diabetes
mellitus.
AB - OBJECTIVE: To investigate the relationship between soluble intercellular adhesion
molecule (sICAM-1), vascular endothelial cell adhesion molecule (VCAM-1),
monocytes chemotactic protein (MCP-1), von Willebrand factor (vWF), and coronary
artery stenoses degree in coronary heart disease (CHD) within type 2 diabetes
mellitus (T2DM) patients. METHODS: A total of 92 subjects were treated with
coronary angiography (CAG), including 62 subjects with CHD. The individuals were
divided into three groups, group A (32 patients with CHD and T2DM), group B (30
patients with CHD but no T2DM) and group C (30 patients with no CHD and T2DM).
All patients were treated with a Gensini coronary angiography check. The
correlations between sICAM-1, VCAM-1, MCP-1 and vWF in peripheral blood and
coronary artery stenosis degree were analyzed. RESULTS: The average score of
coronary artery stenosis degree was 30.75 +/-12.67 in group A, which was
significantly higher than group B (11.20 +/-7.51) and group C (2.40 +/- 1.23) (p
< 0.01). The mean levels of sICAM-1, VCAM-1, MCP-1 and vWF in serum showed that
group A was significantly higher than group B and group C (p < 0.01), and also
that group B was higher than group C. There were significant positive
correlations between the degree of coronary artery stenosis and the mean level of
sICAM-1, VCAM-1, MCP-1, vWF in group A (p < 0.01), but these were not shown in
group B and group C (p > 0.05). CONCLUSIONS: Association analysis shown that the
level of sICAM-1, VCAM-1, MCP-1 and vWF elevated in CHD with T2DM patients.
Vascular endothelial dysfunction could be caused to the coronary artery stenosis
pathophysiological process. Results from this study suggested that sICAM-1, VCAM
1, MCP-1 and vWF may contribute to the occurrence and development of vascular
lesions in T2DM. These endothelial function related factors could be acceptable
as a prediction and testing index of vascular complications in T2DM.
PMID- 23155700
TI - Thyroid autoimmunity in 72 children with type 1 diabetes mellitus: relationship
with pancreatic autoimmunity and child growth.
AB - The aim of this study was to assess the association between pancreatic and
thyroid autoimmunity (TA) and determine impact of thyroid antibodies on statural
growth. Seventy-two children with type 1 diabetes mellitus (TIDM) and no clinical
evidence of thyroid disorders were evaluated: glycated haemoglobin (A1c), thyroid
peroxidase antibodies (TPOAb), glutamic acid decarboxylase antibody (GADA),
tyrosine phosphatase antibodies (IA2A), and thyroid-stimulating hormone (TSH).
The score of standard deviation for height (SDS) was calculated. There were 72
patients, 38 (52.7%) boys and 34 (47.2%) girls, with a mean age of 10.89 +/- 4.26
years and a mean duration of T1DM of 3.41 +/- 2.56 years. TPOAb were present in
23.6% of patients; 12.5% of subjects were positive for GADA and 41.6% for IA2A.
Patients with TA had more prevalent GADA and IA2A (23.5% vs. 9%, p < 0.001, and
58.8% vs. 36.3%, p < 0.001, respectively). A1c was higher in patients with TA
(9.7% +/- 2.05% vs. 8.6% +/- 2.11%, p = 0.05). TA was associated with lower SDS
(0.26 vs. 0.98, p = 0.043). TSH was higher in patients with TA (3.39 vs. 2.15
microU/mL, p < 0.05). Logistic regression analysis revealed that a negative SDS
for height was independently associated with duration of diabetes (p = 0.049) and
TSH (p = 0.027) but not with birth weight, A1c, and TPOAb. In conclusion, TA was
found in 23.6% TIDM children. Patients with TA had significantly higher
prevalence of GADA and IA2A and significantly higher A1c vs. patients without TA.
Our data suggest significant association between TA and height in children with
T1DM. SDS was independently associated with diabetes duration and TSH.
PMID- 23155699
TI - Adiponectin and arterial stiffness in youth with type 1 diabetes: the SEARCH for
diabetes in youth study.
AB - Persons with type 1 diabetes are at increased risk of developing vascular
disease. Adiponectin concentrations may play an intermediate role in this
process. We sought to determine whether adiponectin is correlated with vascular
stiffness in adolescents with type 1 diabetes. Plasma adiponectin, pulse wave
velocity (PWV), augmentation index (AIx-75), and brachial distensibility (BrachD)
were collected in 225 adolescents. Outcomes were evaluated by sex, and regression
models were used to determine whether adiponectin was an independent determinant
of arterial stiffness. Males had lower adiponectin levels and stiffer vessels
(lower BrachD, p < 0.01) than females. Unadjusted correlations revealed that
adiponectin was correlated with BrachD (p < 0.01) but not PWV and AIx-75. After
adjustment, adiponectin was not a significant predictor of BrachD. The most
consistent predictors of increased stiffness were age, male sex, blood pressure,
obesity, and total cholesterol (p < 0.05). Adiponectin's contributions to
arterial stiffness appear to be masked by other cardiovascular risk factors in
persons with type 1 diabetes.
PMID- 23155701
TI - Nesfatin-1 in newborns: relationship with endocrine and metabolic and
anthropometric measures.
AB - OBJECTIVE: To explore the relationship between nesfatin-1 and growth and
development in newborns. METHODS: Blood samples for nesfatin-1, ghrelin,
insulinlike growth factor-1 (IGF-1), insulin and glucose were obtained from
preterm (n = 53) and term infants (n = 60), including appropriate for gestational
age (AGA) (n = 32) and small for gestational age (SGA) infants (n = 28). The
relationship between nesfatin-1 and other metabolic hormones or anthropometric
parameters was evaluated. RESULTS: The concentrations of nesfatin-1, ghrelin and
insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR)
were higher in SGA than AGA infants (p = 0.0358, 0.0163, 0.0001 and 0.0051,
respectively), but IGF-1 levels and homeostasis model assessment-insulin
sensitivity index (HOMA-ISI) were lower (p = 0.033 and 0.0001, respectively).
Nesfatin-1 levels in SGA infants were higher on postnatal day 0 (PNDO) than in
AGA infants (p = 0.0358) and lower on PND7 (p = 0.0002) and PND28 (p = 0.0488). A
negative correlation showed between nesfatin-1 and oral calorie intake (r =
0.446; p = 0.017) and HOMA-ISI (r = -0.398; p = 0.036), and a positive
correlation between nesfatin-1 and HOMA-IR (r = 0.43; p = 0.023) in SGA infants.
CONCLUSION: Nesfatin-1 is involved in the physiological regulation of
intrauterine and postnatal growth and development in SGA infants.
PMID- 23155702
TI - How much is enough? Evaluation of adrenal function in children who undergo growth
hormone stimulation test.
AB - The objective was to determine the probability of receiving steroid treatment
following an insulin tolerance test (ITT) for short-stature evaluation and to
evaluate the utility of a subsequent cortrosyn stimulation test (CST) in
determining adrenal sufficiency. We retrospectively analyzed the hypothalamic
pituitary-adrenal (HPA) axis evaluation in short-stature subjects during the 5
year period from January 2005 to December 2009. The probability of receiving
steroid treatment was < 10% when the maximum cortisol concentration during an ITT
was < 8.4 microg/dL. In the event of a suboptimal cortisol response during an
ITT, only a single 1-microg CST is recommended for assessment of adrenal
function.
PMID- 23155703
TI - A novel mutation in the GCM2 gene causing severe congenital isolated
hypoparathyroidism.
AB - OBJECTIVE: To investigate the GCM2 gene in three siblings with congenital
hypoparathyroidism and perform functional analysis. MATERIALS AND METHODS: We
sequenced the GCM2 gene by PCR and analyzed the functional consequence of the
mutation by transient transfection studies. Haplotype analysis was performed.
RESULTS: We identified a nucleotide change, c.408C>A, in exon 3 that is predicted
to truncate the Gcm2 protein (p.Tyr136Ter). All three affected siblings were
homozygous and both parents were heterozygous for the mutation. Transfection
studies revealed the mutant mRNA but not expression of the Gcm2 protein.
Haplotype analysis revealed that the two mutant GCM2 alleles shared genotypes on
chromosome 6p24.2. CONCLUSIONS: We describe the first GCM2 mutation in exon 3 in
patients with severe congenital hypoparathyroidism. Informative genetic markers
could not exclude identity by descent for the mutant alleles. Gcm2 protein was
not detected after transfection, suggesting that complete lack of Gcm2 action
accounts for severe hypoparathyroidism.
PMID- 23155704
TI - Relation among ghrelin, nutritional status, and immunity in children.
AB - BACKGROUND: Ghrelin is an important mediator of energy balance and metabolism.
The aim of this study was to investigate the relationship among ghrelin
concentration, growth patterns, and immunological parameters in children with an
impairment or inefficiency in functioning of the immune system. METHODS: Twenty
patients with primary immunodeficiency diseases (PIDs), 20 patients with
recurrent respiratory tract infections (RRTIs), and 20 healthy children (control
group) were included. The anthropometric measurements, ghrelin plasma levels, and
selected immunological parameters were measured. RESULTS: Ghrelin levels and
nutritional status parameters (weight, height, and body mass index) values were
negatively correlated only in the control group. Ghrelin negatively correlates
with complement hemolytic activity in the PID group and with IgA serum level in
the RRTI group. CONCLUSION: Our results show evidence that there is a
relationship between ghrelin and nutritional status of healthy children but not
in children with PID or RRTI.
PMID- 23155705
TI - The histopathological effects of tamoxifen in the treatment of pubertal
gynecomastia.
AB - Pubertal gynecomastia is the glandular proliferation of male breast tissue. It is
regarded as a physiological phenomenon, arising due to a presumed transient
imbalance in the ratio of free androgen to free estrogen. Treatment with
tamoxifen, a selective estrogen receptor blocker, has been shown to effectively
reduce the disc size and is generally considered for treatment when the disc
diameter is > 3-4 cm. For severe or persistent cases, surgery is considered the
mainstay of treatment. We present three cases who reported dissatisfaction with
the results of tamoxifen treatment and were therefore submitted to adenectomy by
Webster's technique preceded by liposuction. Pathology results showed adipose
tissue alone, with no evidence of intraductal epithelial proliferation. The
results showing a lack of residual glandular breast tissue after treatment using
tamoxifen proves that it is effective in histopathologically eliminating pubertal
gynecomastia.
PMID- 23155706
TI - Central precocious puberty after interpersonal transfer of testosterone gel: just
a coincidence?
AB - BACKGROUND: Over the last 10 years, several children, fetuses and women have been
reported to be virilized through interpersonal transfer of testosterone (T) gel
used by fathers or partners. Long-term exposure to androgens in children, such as
in poorly controlled congenital adrenal hyperplasia, is known to promote central
precocious puberty. METHODS: Clinical case report. RESULTS: We report on a 5-year
old boy who developed central precocious puberty after long-term (starting
prenatally) exposure to testosterone through interpersonal transfer of T gel used
by his father. We also report on another case illustrating that the recommended
precautions are not sufficient to avoid interpersonal transfer of T gel among
household contacts. Plasma testosterone levels and history-taking revealed the
cause of virilisation and the testosterone contamination source in both cases.
Given the increased testicular volume and persisting testosterone elevation after
cessation of gel use in the first patient, a GnRH test was carried out and
confirmed central precocious puberty. CONCLUSION: This is the first report of a
boy with central precocious puberty occurring after long-term (starting
prenatally) exposure to testosterone through the interpersonal transfer of Tgel.
This report questions whether central precocious puberty constitutes a long-term
side effect of testosterone exposure in childhood through T gel use by a
household contact.
PMID- 23155707
TI - Elevated alpha-fetoprotein levels in Van Wyk-Grumbach syndrome: a case report and
review of literature.
AB - The association between primary hypothyroidism and precocious puberty secondary
to ovarian hyperstimulation has been recognized for over a century. Here, we
report the case of a 9-year-old girl with severe primary hypothyroidism, who
presented with premature menarche, enlarged pituitary gland, enlarged ovaries
with multiple cysts, and elevated prolactin and alpha-feto protein levels.
Pituitary and ovarian radiology findings, and alpha-feto protein levels
normalized a few weeks after hypothyroidism treatment was started. Reviewing the
literature we found several reports of increased levels of tumor markers in girls
with this association. Thyroid function tests should be always part of the
evaluation of patients with precocious puberty especially if the bone age is
delayed. Tumor markers and liver function tests may be abnormal in patients with
severe hypothyroidism and improve soon after thyroid hormone replacement is
started.
PMID- 23155708
TI - Identification of LDLR mutations in two Chinese pedigrees with familial
hypercholesterolemia.
AB - Familial hypercholesterolemia (FH) is an autosomal dominant, inherited disease
(OMIM 143890) characterized by elevated serum cholesterol bound to low-density
lipoprotein (LDL). It is mainly caused by mutations of the low-density
lipoprotein receptor gene (LDLR). In this study, we investigated two Chinese
pedigrees with FH. The probands were a 9-year-old boy and a 1-year-old boy, who
had high LDL-C levels. The proband in family A showed skin xanthoma. We sequenced
the promoter and all exons and exon-intron boundaries of the LDLR gene to detect
potential mutations. Compound heterozygote of c.1747C>T and c.2054C>T was
detected in the proband of family A, and a heterozygous indel mutation c.551_553
delGTAinsTT was discovered in the second family. The c.1747C>T and c.2054C>T
mutations, which have been reported previously, result in His583Tyr and Pro685Leu
substitutions, respectively. The novel c.551_553 delGTAinsTT indel mutation
causes a frameshift, which results in a p.Cys184Phe fs21X mutation in the
corresponding protein.
PMID- 23155709
TI - Foster care and type 1 diabetes in the Bronx: a case series.
AB - OBJECTIVE: The objective of this retrospective study was to describe the health
status of children with type 1 diabetes mellitus (T1DM) in foster care. RESEARCH
DESIGN AND METHODS: A retrospective chart review of children with T1DM in foster
care at the Children's Hospital at Montefiore (CHAM) in Bronx, NY, USA, was
performed. RESULTS: All patients were either African American or Hispanic and
raised by single mothers. The majority of referrals were for medical neglect. The
time spent in foster care ranged from 1 to 7 years, with 1-12 placements. Only
two children were reunified with their biological mothers. Extensive financial
burdens on the health-care system for children with diabetes including prolonged
hospitalizations awaiting placement, frequent hospital admissions, and support
services were noted. CONCLUSIONS: To our knowledge, this is the first report on
children with T1DM in foster care. Poor glycemic control and suboptimal social
outcomes were noted in the children we report in our case series. Programs geared
to improve and reform foster care for children with diabetes are needed.
PMID- 23155710
TI - Primary hyperparathyroidism: fifth parathyroid intrathymic adenoma in a young
patient.
AB - The clinical case described in this paper deals with a young female patient
affected by primary hyperparathyroidism caused by an ectopic parathyroid adenoma
of a supernumerary intrathymic parathyroid. The patient had hypercalcemia, in
association with increased levels of parathormone, but was otherwise
asymptomatic. Genetics tests for mutation of the MEN1, HRPT2, and CaSR genes were
negative. She therefore underwent laboratory and instrumental tests but
localization results in the neck were negative--only an intrathymic nodule was
visualized. The complete surgical ablation of the thymus was conducted, which
highlighted a nodule that, at histological examination, was shown to be an
adenoma of a fifth parathyroid gland. The existence of a fifth, hyperfunctioning,
intrathoracic parathyroid appears to be a rare cause of primary juvenile sporadic
hyperparathyroidism. This peculiar clinical case could be of interest in similar
cases evaluated by other surgeons.
PMID- 23155711
TI - Sturge-Weber syndrome: presentation with partial hypopituitarism.
AB - Sturge-Weber syndrome (SWS) is a rare disorder involving central nervous system
abnormalities. It manifests with a facial port-wine birthmark and a vascular
malformation of the brain. Infants and children present with seizures and stroke
like episodes with focal neurologic deficits. Patients with Sturge-Weber syndrome
carry the additional risk of developing hypothalamic-pituitary dysfunction,
secondary to their central nervous system dysfunction. Although one would suspect
the hypothalamic-pituitary axis would be at risk for impairment given the
abnormalities that often occur in Sturge-Weber syndrome, they are not commonly
recognized by clinicians. Increased awareness of this potential complication in
patients with this rare disease of Sturge-Weber syndrome is needed. We hereby
report a case of SWS with partial hypopituitarism and consider it to be important
that these patients should undergo routine evaluation of pituitary function in
the face of any relevant clinical manifestations.
PMID- 23155712
TI - Self-limiting hematuria following growth hormone provocative testing with
arginine hydrochloride.
AB - Evaluation of growth hormone (GH) deficiency often involves use of agents that
stimulate GH secretion, such as clonidine, glucagon, insulin, levo-dopa or
arginine hydrochloride. We present three pediatric cases of benign, macroscopic
hematuria in children without pre-existing renal disease following GH stimulation
testing with clonidine and arginine hydrochloride. In all cases hematuria
resolved spontaneously within 3-4 days without any intervention. This suggests
that careful observation in such cases is sufficient and additional costly
evaluation may be avoided. Other than six anecdotal cases registered via on-line
adverse event reporting system (AERS), this is the first published report to date
of painless, macroscopic, self-limiting hematuria after arginine hydrochloride
infusion.
PMID- 23155713
TI - First case report of short-chain acyl-CoA dehydrogenase deficiency in China.
AB - Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is a rare autosomal
recessive inborn error of mitochondrial fatty acid oxidation. It is caused by
rare mutations as well as polymorphic susceptibility variants. We describe here
the case of a 1-year-old male patient who had growth and mental retardation,
seizures, and recurring fever since infancy. Urinary gas chromatography/mass
spectrometry (GC/MS) showed elevated levels of ethylmalonic acid. Plasma
acylcarnitines on tandem mass spectrometry (MS/MS) and elevations of C4
cartinitine are consistently present. The two polymorphic susceptibility variants
of the short-chain acyl-CoA dehydrogenase (SCAD) gene, c.625G>A and c.322G>A,
were detected. Because of its highly variable clinical characteristics, there are
no related reports in China. This report broadens the phenotype and genotype of
SCADD in China and underlines the difficulty of diagnosis.
PMID- 23155714
TI - Ganglioneuroblastoma in a young child with Turner syndrome.
AB - X chromosome aneuploidy has been identified as a potential risk factor for the
development of neuroblastic tumors. We report a case of a 4-year-old girl with a
45,X karyotype incidentally discovered to have a large ganglioneuroblastoma on
initial screening ultrasound. The incidence of these tumors in girls with Turner
syndrome as well as their possible relationship to recombinant human growth
hormone treatment is discussed.
PMID- 23155715
TI - MODY2 caused by a novel mutation of GCK gene.
AB - Maturity-onset diabetes of the young type 2 (MODY2) is an autosomal dominant
inherited disease caused by heterozygous inactivating mutations in the
glucokinase (GCK) gene and is characterized by mild noninsulin-dependent fasting
hyperglycemia. It is treated with diet only, and complications are extremely
rare. We present a report of a family with MODY2 caused by a novel
NM_000162.3:c.878T>C mutation in exon 8 of the GCK gene. Testing for MODY2 and
reporting all novel mutations are important to avoid difficulties in the
interpretation of genetic test results and to provide fast and definitive
diagnosis for all patients with this disease.
PMID- 23155716
TI - Variability in the age at diagnosis of diabetes in two unrelated patients with a
homozygous glucokinase gene mutation.
AB - Homozygous mutations in the glucokinase gene (GCK) result in a complete
deficiency of the GCK enzyme, which leads to permanent neonatal diabetes
mellitus. Whilst there has been one report of a patient (with a homozygous
p.T168A) who was diagnosed with diabetes at the age of 2 months, all other cases
were diagnosed with diabetes within the first 2 weeks of life. We now report a
second unrelated patient with the same p.T168A GCK mutation who was diagnosed
with diabetes at the age of 9 months. We conclude that the specific GCK mutation,
as yet unidentified genetic modifiers, and/or environmental factors might have
different effects on pancreatic beta-cell functions, causing variability in the
age at diagnosis of diabetes.
PMID- 23155717
TI - Understanding less than nothing: high-dose vitamin D therapy for treating vitamin
D deficiency.
PMID- 23155718
TI - Risk of violent crime victimization during major daily activities.
AB - Exposure to risk of violent crime is best understood after considering where
people are, what they do, and for how long they do it. This article calculates
Americans' exposure to violent attack per 10 million person-hours spent in
different activities. Numerator data are from the National Crime Victimization
Survey (2003-2008) estimates of violent incidents occurring during nine major
everyday activities. Comparable denominator data are derived from the American
Time Use Survey. The resulting time-based rates give a very different picture of
violent crime victimization risk. Hour-for-hour, the greatest risk occurs during
travel between activities. This general result holds for demographic subgroups
and each type of violent crime victimization.
PMID- 23155719
TI - Social capital, opportunity, and school-based victimization.
AB - This study extends the opportunity theory of victimization to consider the social
capital of adolescents at school. We argue that social capital might act as a
protective factor potentially encompassing both the concepts of guardianship and
target attractiveness. Drawing on a sample of 5395 adolescents interviewed in the
context of the 2007 National Crime Victimization Survey (school crime
supplement), we develop school-specific measures of social capital and
opportunity indicators in predicting violent and theft victimization on school
grounds. The results show that opportunity indicators are strong predictors of
both violent and theft victimization and that social capital is especially
important as a protective factor from violent victimization. More specifically,
the results indicate that students who developed trust relationships with adults
at school benefit from these relationships by avoiding violent encounters with
potential offenders. Implications for opportunity theories of victimization are
discussed.
PMID- 23155720
TI - Recent victimization experiences and continued criminal behaviors: what are the
links for adult drug-involved offenders?
AB - Using data from the multi-site adult drug court evaluation (MADCE), we examined
the relationship between recent victimization experiences and the likelihood of
subsequent criminal behavior among a sample of adult drug-involved offenders. The
MADCE data used in this study involved interviews with 674 men and 284 women at
baseline and then, 18 months later. Multilevel modeling showed that physical
victimizations in the year before baseline, but not sexual victimization
experiences, were associated with self-reported criminal offending behavior 18
months later. All relationships held true despite controlling for respondents'
demographic, criminal history, prior drug-related characteristics, and their
participation in a drug court or comparison site program.
PMID- 23155721
TI - The difficulty in measuring suitable targets when modeling victimization.
AB - Target suitability is a critical theoretical concept for opportunity theory.
Previous research has primarily measured this concept using demographic
characteristics of the study participant, which is problematic. This study
corrects the measurement problem by employing bullying variables as alternative
measures of target suitability because they are arguably better at capturing the
social and psychological vulnerability of the individual that is attracting
motivated offenders. Using three waves (1999, 2001, & 2003) of the National Crime
Victimization Survey (NCVS) School Crime Supplement (SCS), this research explores
the impact of the bullying measures along with demographic characteristics and
lifestyle measures on the likelihood that a student will experience victimization
in school. The findings suggest that the bullying measures are better predictors
of victimization over the demographic characteristics and lifestyle measures for
all three waves. The findings highlight the need for better measures of target
suitability, which capture the social and psychological vulnerability of victims
to explain victimization.
PMID- 23155722
TI - Patterns of victimization between and within peer clusters in a high school
social network.
AB - This study presents a descriptive analysis of patterns of violent victimization
between and within the various cohesive clusters of peers comprising a sample of
more than 500 9th-12th grade students from one high school. Social network
analysis techniques provide a visualization of the overall friendship network
structure and allow for the examination of variation in victimization across the
various peer clusters within the larger network. Social relationships among
clusters with varying levels of victimization are also illustrated so as to
provide a sense of possible spatial clustering or diffusion of victimization
across proximal peer clusters. Additionally, to provide a sense of the sorts of
peer clusters that support (or do not support) victimization, characteristics of
clusters at both the high and low ends of the victimization scale are discussed.
Finally, several of the peer clusters at both the high and low ends of the
victimization continuum are "unpacked", allowing examination of within-network
individual-level differences in victimization for these select clusters.
PMID- 23155723
TI - Does the relationship between depression and intimate partner aggression vary by
gender, victim-perpetrator role, and aggression severity?
AB - Research has shown a consistent link between intimate partner violence (IPV) and
depression, although this association may vary by gender, role in IPV (victim,
perpetrator, or bidirectional), and aggression severity. We evaluated these
factors in a telephone survey of 14,063 Canadians. All three factors were found
to affect the association of depression with IPV. Specifically, depression was
more strongly associated with IPV by a partner (i.e., victimization) for women
but with aggression toward a partner (i.e., perpetration) for men. Severity of
aggression was associated with increased risk of depression for both one-sided
and bidirectional aggression by a partner but more strongly for one-sided
aggression toward a partner. These findings suggest that research, prevention,
and treatment should focus on all roles in IPV, not just male-to-female
aggression.
PMID- 23155724
TI - Multiple victimization experiences, resources, and co-occurring mental health
problems among substance-using adolescents.
AB - This study examined the relationship between multiple types of victimization
experiences, psychological and social resources, and co-occurring mental health
problems among substance-using adolescents. Data for this cross-sectional study
were obtained from a multisite research project in which adolescents ages 11-18
years participated in a comprehensive screening program for substance misuse.
Multiple types of victimization, low self-efficacy beliefs, lack of support for
victimization issues, and available sources of emotional support were positively
related to co-occurring mental health problems. These findings suggest that
treatment planning and interventions may focus on helping adolescents cope
effectively with their victimization experiences and addressing their mental
health needs. Particular emphasis may be placed on enhancing self-efficacy and
social skills so that adolescents may benefit from their available sources of
social support.
PMID- 23155725
TI - A prospective investigation of the relationship between child maltreatment and
indicators of adult psychological well-being.
AB - The study of psychological well-being will advance understanding of child
maltreatment effects and resilience processes. In this study, the mean level of
anger in adulthood was significantly higher for those identified three decades
earlier as having been maltreated. Mean levels of self-esteem, autonomy, purpose
in life, perceived (fewer) constraints, and happiness and satisfaction were lower
for those who were maltreated according to child welfare reports. Officially
recorded child maltreatment was moderately (r < .30) correlated with several
psychological well-being indicators and predictive of adult anger, self-esteem,
autonomy, and happiness/life satisfaction after accounting for childhood
socioeconomic status (SES), gender, and other sources of data on child abuse and
neglect. Parent-reported abusive disciplining also uniquely predicted several
outcomes, as did a measure of observed child neglect to a lesser extent.
PMID- 23155726
TI - An examination of general aggression and intimate partner violence in women with
posttraumatic stress disorder.
AB - Research has documented significant relationships between posttraumatic stress
disorder (PTSD), aggression, and intimate partner violence (IPV). Most of these
studies have focused on men and measured violence by self-report. This study
examined (a) the association between PTSD and general aggression among women, (b)
the association between IPV and PTSD among married and/or cohabitating couples,
and (c) the concordance between self and collateral reports of IPV. One hundred
twenty participants provided information about PTSD symptoms and general
aggression toward others, and 43 married and/or cohabitating couples provided
information about PTSD and IPV. Women with PTSD reported more general aggression,
IPV perpetration, and IPV victimization. Collateral informants of those with and
without PTSD did not differ significantly in their report of IPV. Concordance
between participants and spouses or partners was low to moderate. These results
are discussed within the context of extant IPV literature.
PMID- 23155728
TI - Assessing the relationship between alcohol outlets and domestic violence: routine
activities and the neighborhood environment.
AB - Studies have consistently found a positive relationship between alcohol outlet
density and assault, but only a handful of studies have examined whether outlet
density has an influence on domestic violence. Using a framework based in crime
opportunity theories, this study estimates spatial econometric regression models
to test whether the density of alcohol outlets across neighborhoods is positively
associated with police calls for service for domestic violence. Models also were
developed to test whether the relationships found were consistent across time
periods associated with the use of alcohol outlets (weeknights and weekends). The
findings indicate that off-premise outlets were associated with a significant
increase in domestic violence, but on-premise outlets (specifically restaurants
and nightclubs) were associated with a decrease in domestic violence. The risk
for domestic violence in areas of high densities of off-premise outlets was found
to be high during the weekend but not during the weeknight, suggesting different
routine activities for domestic violence offenders during the week.
PMID- 23155727
TI - Correlates of serious violent crime for recently released parolees with a history
of homelessness.
AB - This study used baseline data on recently released paroled men who are homeless
(N=157), residing in a residential drug treatment program, and enrolled in a
longitudinal study to examine personal, developmental, and social correlates of
parolees who are homeless and who have committed serious violent offenses. Having
experienced childhood sexual abuse, poor parental relationships, and early-onset
incarceration (prior to 21 years of age) were important correlates of serious
violent crimes. These findings highlight the need for interventions that address
offenders' prior adult and childhood victimization and suggest that policies for
reentering violent offenders should encompass an understanding of the broader
family contexts in which these patterns of maltreatment often occur.
PMID- 23155729
TI - Evidence for crossmodal interactions across depth on target localisation
performance in a spatial array.
AB - Auditory stimuli are known to improve visual target recognition and detection
when both are presented in the same spatial location. However, most studies have
focused on crossmodal spatial congruency along the horizontal plane and the
effects of audio-visual spatial congruency in depth (i.e., along the depth axis)
are relatively less well understood. In the following experiments we presented a
visual (face) or auditory (voice) target stimulus in a location on a spatial
array which was either spatially congruent or incongruent in depth (i.e.,
positioned directly in front or behind) with a crossmodal stimulus. The
participant's task was to determine whether a visual (experiments 1 and 3) or
auditory (experiment 2) target was located in the foreground or background of
this array. We found that both visual and auditory targets were less accurately
located when crossmodal stimuli were presented from different, compared to
congruent, locations in depth. Moreover, this effect was particularly found for
visual targets located in the periphery, although spatial incongruency affected
the location of auditory targets across both locations. The relative distance of
the array to the observer did not seem to modulate this congruency effect
(experiment 3). Our results add to the growing evidence for multisensory
influences on search performance and extend these findings to the localisation of
targets in the depth plane.
PMID- 23155730
TI - Height perception influenced by texture gradient.
AB - Three experiments were carried out to examine whether a texture gradient
influences perception of relative object height. Previous research implicated
texture cues in judgments of object width, but similar influences have not been
demonstrated for relative height. In this study, I evaluate a hypothesis that the
projective ratio of the number of texture elements covered by the objects
combined with the ratio of the retinal object heights determines percepts of
relative object height. Density of texture background was varied: four density
conditions ranged from no-texture to very dense texture. In experiments 1 and 2,
participants judged the height of comparison bar compared to the standard bar
positioned on no-texture or textured backgrounds. Results showed relative height
judgments differed with texture manipulations, consistent with predictions from a
hypothesised combination of the number of texture elements with retinal height
(experiment 1), or partially consistent with this hypothesis (experiment 2). In
experiment 2, variations in the position of a comparison object showed that
comparisons located far from the horizon were judged more poorly than in other
positions. In experiment 3 I examined distance perception; relative distance
judgments were found to be also affected by textured backgrounds. Results are
discussed in terms of Gibson's relational theory and distance calibration theory.
PMID- 23155731
TI - Luminance profiles of luminance gradients affect the feeling of dazzling.
AB - The feeling of dazzling that is evoked by luminance gradients was examined. The
stimulus consisted of a disk with uniform luminance surrounded by an annulus
whose luminance was decreased from the inner boundary to the periphery. Three
luminance profiles (linear, logistic, and inverse logistic) of a surrounding
luminance ramp were used. The luminance of the disk and the maximum luminance of
the annulus were also varied. The feeling of dazzling became stronger as the
luminance of the disk and the maximum luminance of the annulus increased. The
effect of the maximum luminance of the annulus was greater for the disk with low
luminance than for that with high luminance. The feeling of dazzling tended to be
greater for the logistic profile than for the other profiles. However, when the
luminance of the disk and that at the inner boundary of the annulus were the
same, the feeling of dazzling for the logistic profile was no stronger than that
for the linear or the inverse-logistic profile. These results suggest that smooth
transition from the disk to the annulus for the logistic profile suppresses the
feeling of dazzling.
PMID- 23155732
TI - Eye and hand movements during reconstruction of spatial memory.
AB - Recent behavioural and biological evidence indicates common mechanisms serving
working memory and attention (e.g., Awh et al, 2006 Neuroscience 139 201-208).
This study explored the role of spatial attention and visual search in an adapted
Corsi spatial memory task. Eye movements and touch responses were recorded from
participants who recalled locations (signalled by colour or shape change) from an
array presented either simultaneously or sequentially. The time delay between
target presentation and recall (0, 5, or 10 s) and the number of locations to be
remembered (2-5) were also manipulated. Analysis of the response phase revealed
subjects were less accurate (touch data) and fixated longer (eye data) when
responding to sequentially presented targets suggesting higher cognitive effort.
Fixation duration on target at recall was also influenced by whether spatial
location was initially signalled by colour or shape change. Finally, we found
that the sequence tasks encouraged longer fixations on the signalled targets than
simultaneous viewing during encoding, but no difference was observed during
recall. We conclude that the attentional manipulations (colour/shape) mainly
affected the eye movement parameters, whereas the memory manipulation (sequential
versus simultaneous, number of items) mainly affected the performance of the hand
during recall, and thus the latter is more important for ascertaining if an item
is remembered or forgotten. In summary, the nature of the stimuli that is used
and how it is presented play key roles in determining subject performance and
behaviour during spatial memory tasks.
PMID- 23155733
TI - The minimal time required to process visual information in visual search tasks
measured by using gaze-contingent visual masking.
AB - To estimate the minimal time required to process visual information (i.e.,
"effective acquisition time") during a visual search task, we used a gaze
contingent visual masking method. In the experiment, an opaque mask that
restricted the central vision was presented at a current gaze position. We
manipulated a temporal delay from a gaze shift to mask movement. Participants
were asked to search for a target letter (T) among distractor letters (L)s as
quickly as possible under various delays. The results showed that the reaction
times and search rate decreased when the delay was increased. When the delay was
longer than 50 ms, the reaction times and search rate reached a plateau. These
results indicate that the effective acquisition time during the visual search
task used in the study is equal to or less than 50 ms. The present study
indicates that the gaze-contingent visual masking method used is useful for
revealing the effective acquisition time.
PMID- 23155734
TI - Subjective contours along truncated letters.
AB - The truncation of upper-case words can result in a subjective contour along the
truncated ends of the letters. We explored this effect in two experiments
designed to tease apart the processes responsible: in particular, the possible
role of letter recognition. Such a role would indicate an unprecedented
involvement of "high-level vision" in the genesis of subjective contours. In
experiment 1, we confirmed the basic effect of word truncation in eliciting a
subjective contour, using only letters where truncation does not eliminate any
critical features. In experiment 2, we showed that the effect is not confined to
words/letters but is equally strong for controlled non-letter stimuli that, like
words, have many forms that have an inflection or an intersection near the
centre. Truncation at one end then introduces proportional imbalance between
upper and lower sections of the figures. We conclude from the two experiments
that part of the effect is due to vertical shortening per se and the rest to the
proportional imbalance introduced by the truncation. The effect of proportional
imbalance, a novel determinant of subjective contours, may result from experience
with letters, although the effect is not "high level" in requiring the
recognition of specific letters.
PMID- 23155735
TI - Evidence for a size underestimation of upright faces.
AB - We quantitatively examined the difference in perceived size between upright and
inverted faces using the method of constant stimuli. The stimuli included eight
face images modified from two cartoon faces produced by Kitaoka (2007,
http://www.psy.ritsumei.ac.jp/-akitaoka/kao-e.html and 2008, Cognitive Psychology
5 177-185) and six photographic faces, including a photographic face used by
Thompson (2010, http://illusionncontest.neuralcorrelate.com/2010/the-fat-face
thin-fft-ilusion/). Experiment 1 showed that an upright face and outline were
perceived to be significantly smaller than an inverted face and outline,
respectively. Moreover, the amount of the size underestimation in the face
stimulus condition was significantly larger than that in the outline stimulus
condition. Experiment 2 showed that an upright face was perceived to be
significantly smaller than 90 degrees and 270 degrees rotated faces, whereas an
inverted face was not perceived to be significantly larger than a 90 degrees or
270 degrees rotated face. Experiment 3 showed that upright faces were perceived
to be significantly smaller than upright and inverted outlines, whereas inverted
faces were not perceived to be significantly larger than upright or inverted
outlines. Experiments 4 and 5 showed that upright photographic faces were also
perceived to be significantly smaller than inverted photographic faces. These
results provide quantitative evidence for a size underestimation of upright
faces.
PMID- 23155736
TI - Associations between auditory pitch and visual elevation do not depend on
language: evidence from a remote population.
AB - Associations between auditory pitch and visual elevation are widespread in many
languages, and behavioral associations have been extensively documented between
height and pitch among speakers of those languages. However, it remains unclear
whether perceptual correspondences between auditory pitch and visual elevation
inform these linguistic associations, or merely reflect them. We probed this
cross-modal mapping in members of a remote Kreung hill tribe in northeastern
Cambodia who do not use spatial language to describe pitch. Participants viewed
shapes rising or falling in space while hearing sounds either rising or falling
in pitch, and reported on the auditory change. Associations between pitch and
vertical position in the Kreung were similar to those demonstrated in populations
where pitch is described in terms of spatial height. These results suggest that
associations between visual elevation and auditory pitch can arise independently
of language. Thus, widespread linguistic associations between pitch and elevation
may reflect universally predisposed perceptual correspondences.
PMID- 23155737
TI - Visual influence on haptic torque perception.
AB - The brain receives input from multiple sensory modalities simultaneously, yet we
experience the outside world as a single integrated percept. This integration
process must overcome instances where perceptual information conflicts across
sensory modalities. Under such conflicts, the relative weighting of information
from each modality typically depends on the given task. For conflicts between
visual and haptic modalities, visual information has been shown to influence
haptic judgments of object identity, spatial features (e.g., location, size),
texture, and heaviness. Here we test a novel instance of haptic-visual conflict
in the perception of torque. We asked participants to hold a left-right
unbalanced object while viewing a potentially left-right mirror-reversed image of
the object. Despite the intuition that the more proximal haptic information
should dominate the perception of torque, we find that visual information exerts
substantial influences on torque perception even when participants know that
visual information is unreliable.
PMID- 23155738
TI - Specular vision-touch synaesthesia: two reference frames.
AB - Two subtypes of vision-touch synaesthesia (VTS) have been identified. For
anatomical VTS, sight of touch on another person elicits synaesthetic tactile
sensation at the same location on the observer's own body (e.g., viewed touch on
the left cheek elicits sensation on the observer's left cheek). For specular VTS,
sight of touch on another person elicits synaesthetic tactile sensation at the
mirror-reflected location (e.g., viewed touch on the left cheek elicits sensation
on the observer's right cheek). Here we report two distinctly different patterns
of sensation within the specular subtype. Both participants experienced
synaesthetic tactile sensation on their right hand when they viewed
unidirectional brushstrokes administered to a prosthetic left hand (positioned
with fingers pointing toward the participant), but the direction of sensation
matched the viewed touch in a hand-centred (spatial) reference frame for RS and
in an external (viewer-centred) reference frame for NC. Competing reference
frames affect how individuals with specular VTS experience synaesthetic tactile
sensation.
PMID- 23155739
TI - Emotional sounds influence vertical vection.
AB - While viewing a large vertically moving sinusoidal luminance grating, the
perception of upward self-motion (vection) was modulated by positive sounds
(e.g., a baby's laughter). This may be because positive emotion and the spatial
metaphor of vertical directions were unified in the mind.
PMID- 23155740
TI - Interpolation of illusory pain in the human somatosensory system.
AB - Three coins are lined up with the middle coin at room temperature and flanking
coins cooled down to 4 degrees C. If digits 2 and 4 are placed on the outer coins
and digit 3 on the middle coin, the latter also feels cold; a striking example of
perceptual filling in of temperature. We show that if digits 2 and 4 are placed
on a thermal grill with alternating hot and cold bars, while digit 3 is placed on
cardboard, the sensation of pain will also spread to the middle finger.
PMID- 23155741
TI - A comparison of the capital structures of nonprofit and proprietary health care
organizations.
AB - The relative amount of debt used by an organization is an important determination
of the organization's likelihood of financial problems and its cost of capital.
This study addresses whether or not there are any differences between proprietary
and nonprofit health care organizations in terms of capital structure.
Controlling for profitability, risk, growth, and size, analysis of covariance is
used to determine whether or not proprietary and nonprofit health care
organizations use the same amount of leverage in their capital structures. The
results indicate that there is no difference in the amount of leverage between
the two institutional types. Although nonprofit and proprietary organizations
have unique financing mechanisms, these differences do not impact the relative
amount of debt and equity in their capital structures.
PMID- 23155742
TI - A comparative analysis of the CVP structure of nonprofit teaching and for-profit
non-teaching hospitals.
AB - Due to the market turbulence facing the hospital industry, the financial
viability of teaching hospitals has been severely threatened. Their missions of
education, research, and patient care even strengthen this crisis. Therefore, the
objective of this study is to conduct a comparative analysis of the cost, volume,
and profit (CVP) structure between large nonprofit urban teaching hospitals and
small for-profit rural/suburban non-teaching hospitals. The following two
hypotheses were developed: (1) large nonprofit urban teaching hospitals tend to
have higher fixed cost, lower variable cost, lower total revenue adjusted by case
mix index (CMI), and lower return on total assets (ROA); and (2) small for-profit
rural/suburban non-teaching hospitals tend to have lower fixed cost, higher
variable cost, higher total revenue adjusted by CMI, and higher ROA. Using 117
teaching hospitals and 102 non-teaching hospitals selected from the Medicare Cost
Report database in 2005, the results from multiple regression indicated that
large nonprofit teaching hospitals located in urban areas are more likely to have
higher fixed cost and lower variable cost. While such cost structure doesn't
necessarily affect their total revenue adjusted by CMI, it does lead to a lower
return on hospitals' total assets. The results support our hypotheses in terms of
fixed cost percentage, variable cost percentage, and ROA, but not total revenue
adjusted by CMI. The results suggest that cost structure is significantly
associated with hospitals' performance. Also, as teaching hospitals' portfolios
of services and programs increase (e.g., provision of uncompensated care to
Medicare and Medicaid patients and doing research), it becomes strategically
necessary and critical to manage the allocation of resources or investments into
the fixed capital that supports the business.
PMID- 23155743
TI - The economics of health care quality and medical errors.
AB - Hospitals have been looking for ways to improve quality and operational
efficiency and cut costs for nearly three decades, using a variety of quality
improvement strategies. However, based on recent reports, approximately 200,000
Americans die from preventable medical errors including facility-acquired
conditions and millions may experience errors. In 2008, medical errors cost the
United States $19.5 billion. About 87 percent or $17 billion were directly
associated with additional medical cost, including: ancillary services,
prescription drug services, and inpatient and outpatient care, according to a
study sponsored by the Society for Actuaries and conducted by Milliman in 2010.
Additional costs of $1.4 billion were attributed to increased mortality rates
with $1.1 billion or 10 million days of lost productivity from missed work based
on short-term disability claims. The authors estimate that the economic impact is
much higher, perhaps nearly $1 trillion annually when quality-adjusted life years
(QALYs) are applied to those that die. Using the Institute of Medicine's (IOM)
estimate of 98,000 deaths due to preventable medical errors annually in its 1998
report, To Err Is Human, and an average of ten lost years of life at $75,000 to
$100,000 per year, there is a loss of $73.5 billion to $98 billion in QALYs for
those deaths--conservatively. These numbers are much greater than those we cite
from studies that explore the direct costs of medical errors. And if the estimate
of a recent Health Affairs article is correct-preventable death being ten times
the IOM estimate-the cost is $735 billion to $980 billion. Quality care is less
expensive care. It is better, more efficient, and by definition, less wasteful.
It is the right care, at the right time, every time. It should mean that far
fewer patients are harmed or injured. Obviously, quality care is not being
delivered consistently throughout U.S. hospitals. Whatever the measure, poor
quality is costing payers and society a great deal. However, health care leaders
and professionals are focusing on quality and patient safety in ways they never
have before because the economics of quality have changed substantially.
PMID- 23155744
TI - Complicated billing requirements challenge physical therapy industry, creating
inefficiencies and confusion.
AB - This article is designed to explain the subtle differences between the
reimbursement requirements for coverage of physical therapy services in physician
based settings under the Medicare benefit policy manual chapter 15--covered
medical and other health services. These billing challenges have a profound
financial impact on the physical therapy industry. This article includes: (1) a
general back ground of the reasons surrounding the increased regulations in the
physical therapy industry; (2) general definitions within the physical therapy
industry; (3) a discussion of the confusing and complicated bill ing requirements
for physical therapy services; (4) a discussion of the "incident to" billing
requirements within the physical therapy billing requirements; (5) an explanation
of differing rules or policies within the physical therapy billing requirements;
and (6) a discussion of why these rules regarding physical therapy billing
requirements are essential to the delivery of quality of care within the physical
therapy industry.
PMID- 23155745
TI - Americans with Disability Act: financial aspects of reasonable accommodations and
undue hardship.
AB - The Americans with Disability Act (ADA) is a significant piece of discrimination
legislation that merits ongoing managerial exploration. This civil rights
legislature indicates that employers are expected to provide reasonable
accommodations to employees with reported disabilities. The statute also
indicates that employers can refuse to offer a reasonable accommodation if doing
so creates an undue hardship on the organization. However, health care managers
should exercise extreme caution when using undue hardship as a defense against
providing reasonable accommodations to employees with disabilities. This point
should be duly noted by health care managers given that studies indicate that
lawsuits alleging disability discrimination are on the rise. This is unfortunate
given the costs of reasonable accommodations are typically miniscule.
PMID- 23155746
TI - A real options approach to clinical faculty salary structure.
AB - One can use the option theory model originally developed to price financial
opportunities in security markets to analyze many other economic arrangements
such as the salary structures of clinical faculty in an academic medical center
practice plan. If one views the underlying asset to be the portion (labeled
"salary") of the economic value of the collections made for the care provided
patients by the physician, then a salary guarantee can be considered a put option
provided the physician, the guarantee having value to the physician only when the
actual salary earned is less than the salary guarantee. Similarly, within an
incentive plan, a salary cap can be thought of as a call option provided to the
practice plan since a salary cap only has value to the practice plan when a
physician's earnings exceed the cap. Further, based on analysis of prior
earnings, the Black-Scholes options pricing model can be used both to price each
option and to determine a financially neutral balance between a salary guarantee
and a salary cap by equating the prices of the implied put and call options. We
suggest that such analysis is superior to empirical methods for setting clinical
faculty salary structure in the academic practice plan setting.
PMID- 23155747
TI - [Botulism].
AB - Botulism is a rare but potentially life-threatening disease caused by Clostridium
botulinum neurotoxin. In Finland only a few cases have been diagnosed during the
past ten years but mild cases may be underdiagnosed. The diagnosis of botulism is
clinical. Patients present with weakness in muscles innervated by the cranial
nerves. In more severe cases the paralysis gradually progresses in a descending
order and may affect respiratory muscles leading to mechanical ventilation.
Routine laboratory tests or radiology are unhelpful in initial diagnostics. A
practicing physician should administrate botulinum antitoxin immediately when
food-borne botulism is suspected since it may be life-saving.
PMID- 23155748
TI - [Liver disease and hemostasis--evaluation of bleeding risk].
AB - In severe liver disease, simultaneous abnormalities in procoagulant and
anticoagulant pathways seem to maintain the hemostatic balance, provided that the
platelet level is sufficient. Common coagulation screening tests such as INR fail
to measure the concomitant anticoagulant deficiencies and fibrinolytic
abnormalities, and do not predict bleeding in patients with compensated liver
disease undergoing invasive procedures. Thus, specific INR cut-off levels and
prophylactic use of fresh-frozen plasma are discouraged. Volume expansion,
hemodynamic disruption, endothelial dysfunction, and infections increase the
bleeding risk. Individualized bleeding risk assessment mandates evaluation of the
patient's clinical condition and a comprehensive assessment of the hemostatic
system.
PMID- 23155749
TI - [Risk of obstetric anal sphincter injury in vaginal births could be reduced].
AB - Obstetric anal sphincter injury (OASIS) is a well-known, serious complication of
vaginal delivery that can have serious implications for women's subsequent
health. The risk factors for OASIS included first vaginal delivery, high
birthweight, prolonged second stage of birth, and operative vaginal deliveries.
Manual perineum protection and use of mediolateral or lateral episiotomy
decreased the risk of OASIS. However, in the order of 99-1000 women must be
exposed to an episiotomy in vaginal deliveries, and 13-67 in operative vaginal
deliveries to prevent a single OASIS. The results indicate the value of selective
use of medio-lateral/lateral episiotomy in spontaneous vaginal iberal use of
deliveries whereas more I it might be advisable in operative vaginal deliveries.
PMID- 23155750
TI - [MODY diabetes--a monogenic developmental and functional disturbance of
pancreatic beta cells].
AB - MODY (Maturity-Onset Diabetes of the Young) is a group of monogenic disorders
characterized by autosomally dominantly inherited diabetes or hyperglycemia
typically detected during adolescence or young adulthood. Usually there is at
least one person in the family having developed the disease at the age of under
25 years, and the patients are diagnosed with insufficient insulin response to
glucose, occasionally also with developmental disturbances of various organs. The
most common form is GCK-MODY caused by glucokinase mutations, primarily
manifested as elevated fasting glucose levels, usually without the risk of
complicating diseases.
PMID- 23155751
TI - [Cystic kidney disease and diabetes--an underdiagnosed monogenic developmental
disorder].
AB - Heterozygous mutations in the TCF2 gene encoding the transcription factor HNF-11
cause a dominantly inherited developmental disorder that may be associated with
various dysplastic and cystic lesions of the kidneys and renal insufficiency,
disorder of pancreatic development and insulin-deficient MODY diabetes, aberrant
hepatic enzyme levels, gout and genital anomalies. Symptoms and findings vary in
their degree of severity. When an isolated abnormality is detected, recognition
of the syndrome is essential in order to diagnose the other organ manifestations.
Since the mid-2000's, 10 to 20 patients have been diagnosed in Finland.
PMID- 23155752
TI - [Reconstructive surgery of leg ulceration].
AB - The great majority of chronic leg ulcers are caused by disturbances of venous and
arterial circulation in the lower extremities. Diagnostics and treatment of
ulcers require multiprofessional collaboration. The cornerstone of the treatment
is conservative treatment intervening in the underlying causes of the ulceration.
If the ulcer is large or recovery does not take place with appropriate
conservative therapy, reconstructive surgery may come into question, i.e.
surgical excision of the ulcer and its covering with a skin graft.
PMID- 23155753
TI - [Outcome of childhood cancer in Tampere, Finland].
AB - BACKGROUND: We investigated the outcome of childhood cancer within the Tampere
University Hospital area, Finland. PATIENTS AND METHODS: We collected the data
from 291 patients, who were 0 to 16 years of age at the time of cancer diagnosis
in 1997 to 2006. The largest diagnosis groups were leukemias, malignant tumors of
the central nervous system, and lymphomas. RESULTS: Altogether 83% of the
patients were alive and at least under long-term remission at the time of the
study. CONCLUSIONS: Outcome of childhood cancer in Tampere University Hospital
area is in line with international results.
PMID- 23155754
TI - [Increased risk of tromboembolic complication in patients with inflammatory bowel
disease].
AB - Tromboembolic complications are 2-4-fold more likely in patients with
inflammatory bowel disease (IBD) than in healthy individuals; active IBD may
increase the relative risk even 15-fold. Deep vein thrombosis and pulmonary
embolism are the most common involvements, but also atypical forms occur. We
describe such uncommon thrombotic manifestations in two IBD patients: one had
mesenterial vein and the other cavernoid sinus thrombosis. The risk of thrombotic
complications should be estimated individually, and prophylactic management with
low molecular weight heparin should be considered in hospitalized IBD patients.
PMID- 23155755
TI - ["With all measures...". Appeal proceedings and political specialty disputes
about orthopedics at the Berlin University and the Charite during the time of the
Kaiser Empire, the Weimar Republic and national socialism].
AB - In 1934 the NSDAP University-Commission forced the president of the German
Society of Surgery and the chairman of the German Orthopaedic Society to sign a
reconciliation agreement. First of all, orthopaedists and surgeons were ordered
to refrain from attacking each other in public. In the future, in the event of
any complaints, they were to address the 'Reichsarztefuhrung' at the Ministry of
the Interior. On the basis of papers and documents from the archives of the
medical faculty, the East German Ministry for State Security and the former
Berlin Document Centre, this article describes the history of the emerging
medical specialty orthopaedics at the University of Berlin and the Charite
hospital. It covers a period from 1890 through 1945 and focuses on the varying
relations between political authorities, medical associations and the faculty.
The main attention is given to ethical and economic disputes and to the way in
which professors for orthopaedics were appointed. The two pioneers of orthopaedic
surgery, Julius Wolff and Albert Hoffa had to overcome less resistance than their
successors Georg Joachimsthal and Hermann Gocht. Gocht's fate changed, when the
NSDAP took Power. As a protege of the regime he represented the medical faculty
during the period of political cleansing. In 1937 the appointment of the
orthopaedist Lothar Kreuz as a full member of the medical faculty was no longer a
university matter anymore. His appointment was negotiated entirely within the
organisations of the NSDAP. Politically approved, Kreuz served as dean of the
medical faculty and later was to be the last rector of the University of Berlin.
For the first time, this article documents the connections between Kreuz, the
paramilitary squadron of the party SS, and key political figures.
PMID- 23155756
TI - [On the astrology and computation in the 12th century: new unpublished
manuscripts ].
AB - This article examines three so far unknown lemmatic commentaries on computus and
on astrolabe topics, which are to be found in MS Stuttgart, Wurttembergische
Landesbibliothek, Cod. math. 4 degrees 33 (second half of the twelfth-century).
The commentaries are on the 'Compotus' by Gerlandus, on the 'De mensura
astrolabii' by Hermann of Reichenau, and on the 'De utilitatibus astrolabii',
which is sometimes attributed to Gerbert of Aurillac. No commentaries on the
respective treatises have previously been identified as such. The commentaries of
the Stuttgart manuscript are of special interest in that they allow us to
understand how a twelfth-century scholar read works on computus and the
astrolabe, namely works that date back to the eleventh century. Their author
remains anonymous, but in all probability he wrote his commentary on the
'Compotus' by Gerlandus either in 1143 or in 1150. An appendix to the article
includes transcriptions of the introductory texts on the computus and on the
astrolabe as well as the beginnings of the commentaries.
PMID- 23155757
TI - [Reference relationships between human and animal in Hildegard von Bingen].
AB - In "De animalibus", the 7th book in the "Liber simplicis medicinae", Hildegard
von Bingen describes the characteristics of four-footed land animals. Some of
these have a special relationship with humans in that they embody moral
qualities. An explanation for this is already given in the preface, which states
that human intelligence recognizes these qualities, declaring that "You are this
or that sort of creature". Since the relationship that animals have with nature
shares a degree of similarity with that of man's, they can be regarded as
symbolic representatives for particular human traits and characteristics. The
article at hand presents Hildegard von Bingen's descriptions of the monkey, the
lion, the bear, the rabbit, the dog, the cat, the wolf, the lynx, and the donkey.
While the monkey just mimics man's behaviour and is imperfect in both settings,
the lion embodies will power. The bear on the other hand stands for unbridled
sexual desire, while in the rabbit the gentleness of a sheep is united with the
bounce of a deer. The lynx is regarded as hedonistic, the donkey as stupid, and
the wolf as surrounded by dangerous sylphs. In Hildegard's depictions, exotic and
native animal species display rather extraordinary behavioural traits, and the
medieval Christian world view of the author conveys unexpected relationships
between humans and animals. In addition to empirical observation and experience,
Hildegard also relies on folkloristic beliefs and magical practices related to
explanatory models of her time. She allows largely unknown sources into her
animal lore but never strays from her ultimate goal of having it serve to
instruct people. In doing so, Hildegard removed herself far from the common
tradition of medieval animal portraits.
PMID- 23155758
TI - K. 263+10934, A tablet with recipes against the abnormal flow of a woman's blood.
PMID- 23155759
TI - ["Could not therefore the earth globe also be a large tourmaline?" A crystal,
Lichtenberg and the polarity discussion before 1800].
AB - This paper focuses on the debate on one particular phenomenon of the research
into electrical charge distribution prior to 1800: the description and
interpretation of polarities observed on the tourmaline. We show that in the
second half of the eighteenth century this crystal became a model to distinguish
and categorize different qualities of charges (electric and magnetic fluids). It
will become clear that the polarity detected on the tourmaline became a key
concept for eighteenth century natural philosophy, which relied on analogizing
operations. We illustrate this concentrating on Lichtenbergs first lecture at the
Gottingen academy of science in 1778. Thus the concept of polarity is already a
central ordering category before the beginnings of the speculative enterprise of
idealistic Naturphilosophy. Consequently, the physicist Johann Wilhelm Ritter,
who can be positioned in that context, consciously adheres to the experimental
research tradition of polarities portrayed in this paper.
PMID- 23155760
TI - A hybrid approach to gene ranking using gene relation networks derived from
literature for the identification of disease gene markers.
AB - For the identification of gene markers involved in diseases, microarray
expression profiles have been widely used to prioritize genes. In this paper, we
propose a novel approach to gene ranking that employs gene relation network
derived from literature along with microarray expression scores to calculate
ranking statistics of individual genes. In particular, the gene relation network
is constructed from literature by applying syntactic analysis and co-occurrence
method in a hybrid manner. For evaluation, the proposed method was tested with
publicly available prostate cancer data. The result shows that our method is
superior to other existing approaches.
PMID- 23155761
TI - Tri-mean-based statistical differential gene expression detection.
AB - Based on the assumption that only a subset of disease group has differential gene
expression, traditional detection of differentially expressed genes is under the
constraint that cancer genes are up- or down-regulated in all disease samples
compared with normal samples. However, in 2005, Tomlins assumed and discussed the
situation that only a subset of disease samples would be activated, which are
often referred to as outliers.
PMID- 23155762
TI - MicroRNAfold: pre-microRNA secondary structure prediction based on modified NCM
model with thermodynamics-based scoring strategy.
AB - An accurate prediction of the pre-microRNA secondary structure is important in
miRNA informatics. Based on a recently proposed model, nucleotide cyclic motifs
(NCM), to predict RNA secondary structure, we propose and implement a Modified
NCM (MNCM) model with a physics-based scoring strategy to tackle the problem of
pre-microRNA folding. Our microRNAfold is implemented using a global optimal
algorithm based on the bottom-up local optimal solutions. Our experimental
results show that microRNAfold outperforms the current leading prediction tools
in terms of True Negative rate, False Negative rate, Specificity, and Matthews
coefficient ratio.
PMID- 23155763
TI - Genome-wide identification and evolutionary analysis of B7-H3.
AB - B7-H3 is an immune co-stimulatory molecule of the B7 family that contains a set
of immunoglobulin-V (IgV) and immunoglobulin-C (IgC) domains. To explore the
evolutionary process of B7-H3 gene, we conducted a genome-wide structure and
phylogenetic analysis of B7-H3 genes in currently sequenced genomes. On the basis
of the available data, 17 mammalian B7-H3 genes were predicted to have tandemly
duplicated 4Ig domains. The analysis of gene structure and phylogenesis reveal
that these 4IgB7-H3 genes resulted from domain duplication. Nevertheless, no
difference in function has been observed between the two isoforms. It is more
likely that domain duplication in 4IgB7-H3 leads to functional redundancy.
PMID- 23155764
TI - A new clustering approach for learning transcriptional modules.
AB - In modern biology, we had an explosion of genomic data from multiple sources,
like measurements of RNA levels, gene sequences, annotations or interaction data.
These heterogeneous data provide important information that should be integrated
through suitable learning methods aimed at elucidating regulatory networks. We
propose an iterative relational clustering procedure for finding modules of co
regulated genes. This approach integrates information concerning known
Transcription Factors (TFs)--gene interactions with gene expression data to find
clusters of genes that share a common regulatory program. The results obtained on
two well-known gene expression data sets from Saccharomyces cerevisiae are shown.
PMID- 23155765
TI - Select your SNPs (SYSNPs): a web tool for automatic and massive selection of
SNPs.
AB - Association studies are the choice approach in the discovery of the genomic basis
of complex traits. To carry out such analysis, researchers frequently need to (1)
select optimally informative sets of Single Nucleotide Polymorphisms (SNPs) in
candidate regions and (2) annotate the results of associations found by means of
genome-wide SNP arrays. These are complex tasks, since many criteria have to be
considered, including the SNPs' functional properties, technological information
and haplotype frequencies in given populations. SYSNPs implements algorithms that
allow for efficient and simultaneous consideration of all the relevant criteria
to obtain sets of SNPs that properly cover arbitrarily large lists of genes or
genomic regions. Complementarily, SYSNPs allows for comprehensive functional
annotation of SNPs linked to any given marker SNP. SYSNPs dramatically reduces
the effort needed for SNP selection from days of searching various databases to a
few minutes using a simple browser.
PMID- 23155766
TI - Hybrid softcomputing model for lesion identification and information combination:
some case studies.
AB - Authors present segmentation and information combination of section of human
brain images. Improved hybrid algorithm is presented for clustering, which
integrates the concept of Rough sets, Fuzzy sets incorporated with probabilistic
as well as possibilistic memberships. The segmented images are fused using
wavelet and curvelet based techniques. Lower and upper approximations of Rough
sets handle uncertainty, vagueness, and incompleteness in class definition. To
accelerate the segmentation process, the RFPCM has been equipped with membership
suppression mechanism, which creates competition among clusters to speed-up the
clustering process using MR T1 and MR T2 images of section of human brain.
PMID- 23155767
TI - Agent-based model of macrophage action on endocrine pancreas.
AB - This paper proposes an agent-based model of the action of macrophages on the beta
cells of the endocrine pancreas. The aim of this model is to simulate the
processes of beta cell proliferation and apoptosis and also the process of
phagocytosis of cell debris by macrophages, all of which are related to the onset
of the autoimmune response in type 1 diabetes. We have used data from the
scientific literature to design the model. The results show that the model
obtains good approximations to real processes and could be used to shed light on
some open questions concerning such processes.
PMID- 23155768
TI - An integrative approach for codon repeats evolutionary analyses.
AB - The relationship between genome characteristics and several human diseases has
been a central research goal in genomics. Many studies have shown that specific
gene patterns, such as amino acid repetitions, are associated with human
diseases. However, several open questions still remain, such as, how these tandem
repeats appeared in the evolutionary path or how they have evolved in orthologous
genes of related organisms. In this paper, we present a computational solution
that facilitates comparative studies of orthologous genes from various organisms.
The application uses various web services to gather gene sequence information,
local algorithms for tandem repeats identification and similarity measures for
gene clustering.
PMID- 23155769
TI - An integrated computational environment for elementary modes analysis of
biochemical networks.
AB - Elementary flux modes (EFMs) have been claimed as one of the most promising
approaches for pathway analysis. These are a set of vectors that emerge from the
stoichiometric matrix of a biochemical network through the use of convex
analysis. The computation of all EFMs of a given network is an NP-hard problem
and existing algorithms do not scale well. Moreover, the analysis of results is
difficult given the thousands or millions of possible modes generated. In this
work, we propose a new plug-in, running on top of the OptFlux Metabolic
Engineering workbench (Rocha et al., 2010), whose aims are to ease the analysis
of these results and explore synergies among EFM analysis, phenotype simulation
and strain optimisation. Two case studies are shown to illustrate the
capabilities of the proposed tool.
PMID- 23155770
TI - A comparative-based phylogenetic study in the evolution of 16S rRNA and rad a
genes in Archaea.
AB - Archaea are ubiquitous in their presence and abundant not only in extreme
environments, but also in soil, oceans and freshwater, where they may fulfil a
key role in the biogeochemical cycles of the earth. The identification of
archaeal genomic signatures elucidates us a measure of distinctiveness of Archaea
as a coherent group, although these signatures can differ according to the degree
of stringency. The 16S rRNA and the Rad A genes are highly conserved in living
organisms and are very useful for the phylogenetic analysis. Phylogenetic trees
are constructed using the molecular evolutionary genetics analysis (MEGA) tool by
neighbour joining (NJ) method and repeated bootstrapping for 5000 times was
performed. The two trees were then compared using the Compare2trees and
statistically analysed using the MEGA tool. The two phylogenetic trees show a
similarity of 54.9%. In both the trees, the taxon Thaumarchaeota shows a high
level of variance. The species Cenarchaeum symbiosum A shows a high level of
similarity with the sequences of higher organisms (Euryarcheota-eukaryota), which
shows that it has branched away to higher organisms from a closely related
Protozoa, Eubacteria ancestor.
PMID- 23155771
TI - Mining poly-regions in DNA.
AB - We study the problem of mining poly-regions in DNA. A poly-region is defined as a
bursty DNA area, i.e., area of elevated frequency of a DNA pattern. We introduce
a general formulation that covers a range of meaningful types of poly-regions and
develop three efficient detection methods. The first applies recursive
segmentation and is entropy-based. The second uses a set of sliding windows that
summarize each sequence segment using several statistics. Finally, the third
employs a technique based on majority vote. The proposed algorithms are tested on
DNA sequences of four different organisms in terms of recall and runtime.
PMID- 23155772
TI - Semi-supervised clustering algorithm for haplotype assembly problem based on MEC
model.
AB - Haplotype assembly is to infer a pair of haplotypes from localized polymorphism
data. In this paper, a semi-supervised clustering algorithm-SSK (semi-supervised
K-means) is proposed for it, which, to our knowledge, is the first semi
supervised clustering method for it. In SSK, some positive information is firstly
extracted. The information is then used to help k-means to cluster all SNP
fragments into two sets from which two haplotypes can be reconstructed. The
performance of SSK is tested on both real data and simulated data. The results
show that it outperforms several state-of-the-art algorithms on minimum error
correction (MEC) model.
PMID- 23155773
TI - Extracting epidemiologic exposure and outcome terms from literature using machine
learning approaches.
AB - Much epidemiologic information resides in literature, which is not in a
computable format. To extract information and build knowledge bases of
epidemiologic studies, we developed a system to extract noun phrases about
epidemiologic exposures and outcomes. The system consists of two components: a
natural language processing (NLP) engine; a machine learning (ML) based
classifier. Four ML algorithms were applied and compared over different feature
sets. To evaluate the performance of the system, we manually constructed an
annotated dataset. The system achieved the highest F-measure of 82.0% for
extracting exposure terms, and 70% for extracting outcome terms.
PMID- 23155774
TI - Data mining for high throughput data from genome-wide association studies.
PMID- 23155775
TI - Support vector machines with L1 penalty for detecting gene-gene interactions.
AB - Interactions among genetic variants are likely to affect risk for human complex
diseases, and their identification should increase the power to detect disease
associated variants and elucidate biological pathways underlying diseases. We
propose a two-stage approach: model selection with support vector machines
identifies the most promising single nucleotide polymorphisms and interactions;
logistic regression ensures a valid type I error by excluding non-significant
candidates after Bonferroni correction. Simulation studies for case-control data
suggest that our method powerfully detects gene-gene interactions. We analyze a
published genome-wide case-control dataset, where our method successfully
identifies an interaction term, which was missed in previous studies.
PMID- 23155776
TI - cuGWAM: Genome-wide association multifactor dimensionality reduction using CUDA
enabled high-performance graphics processing unit.
AB - Multifactor dimensionality reduction (MDR) method has been widely applied to
detect gene-gene interactions that are well recognized as playing an important
role in understanding complex traits. However, because of an exhaustive analysis
of MDR, the current MDR software has some limitations to be extended to the
genome-wide association studies (GWAS) with a large number of genetic markers up
to approximately 1 million. To overcome this computational problem, we developed
CUDA (Compute Unified Device Architecture) based genome-wide association MDR
(cuGWAM) software using efficient hardware accelerators, cuGWAM has better
performance than CPU-based MDR methods and other GPU-based methods.
PMID- 23155777
TI - Multilocus association analysis under polygenic models.
AB - For each variant in a genome-wide association study, the risk allele is the one
with an odds ratio greater than 1. For a given set of variants, the number of
risk alleles in cases minus that in controls is evaluated and a p-value is
obtained for this difference. Successive sums of these differences over the best
2, 3, etc. variants and associated p-values are obtained. The smallest such p
value is our genome-wide test statistic, for which an empirical significance
level is obtained by permutation analysis. Applied to disease datasets, our
approach furnishes significant results even with little single-locus effects.
PMID- 23155778
TI - Unbalanced sample size effect on genome-wide population differentiation studies.
AB - The fixation index (F(ST)) is one of the most widely used measurements of genetic
distance between populations. The data set from the international HapMap project
has been served as a reference data set for population differentiation studies.
F(ST) is commonly used in order to compare the sample data with HapMap data. In
this study, however, we show that the use of F(ST) without consideration of
sample sizes may mislead the result. In particular, we first demonstrate that
F(ST) suffers from imbalance of sample sizes through simulation studies and
through the analysis of a large scale Korean genome-wide association data. Then,
we propose a modified version of F(ST) which is shown to be more robust to
imbalance of sample size. In addition, the chi-square test commonly used for
homogeneity test is shown to perform similarly to the modified version of F(ST).
PMID- 23155779
TI - Pattern discovery of multivariate phenotypes by association rule mining and its
scheme for genome-wide association studies.
AB - Genome-wide association studies (GWAS) have served crucial roles in investigating
disease susceptible loci for single traits. On the other hand, GWAS have been
limited in measuring genetic risk factors for multivariate phenotypes from
pleiotropic genetic effects of genetic loci. This work reports a data mining
approach to discover patterns of multivariate phenotypes expressed as association
rules, and presents an analytical scheme for GWAS of those newly defined
multivariate phenotypes. We identified 13 SNPs for four genes (CSMD1, NFE2L1,
CBX1, and SKAP1) associated with a new multivariate phenotype defined as low
levels of low density lipoprotein cholesterol (LDL-C < or = 100 mg/dl) and high
levels of triglycerides (TG > or = 180 mg/dl). Compared with a traditional
approach to GWAS, the use of discovered multivariate phenotypes can be
advantageous in identifying pleiotropic genetic risk factors, which may have a
common etiological role for the multivariate phenotypes.
PMID- 23155780
TI - Selecting SNPs for pharmacogenomic association study.
AB - SNP genotyping device is an essential tool in the upcoming era ofpersonal genome
and personalised medicine. Human genome has more than 10 million SNPs whereas
conventional SNP genotyping device can only hold 1 million SNPs. Thus,
intelligent SNP contents selection is required to maximise the value of SNP
genotyping device. Here, we developed a new selection algorithm and applied this
method to design genotyping contents for cancerand pharmacogenomic association
study. This approach significantly increased the product value when compared with
contents of competitive SNP genotyping product.
PMID- 23155781
TI - A 2-phased approach for detecting multiple loci associations with traits.
AB - The recent advance in SNP genotyping has made a significant contribution to
reduction of the costs for large-scale genotyping. The development also has
dramatically increased the size of the SNP genotype data. The increase in the
volume of the data, however, has posed a huge obstacle to the conventional
analysis techniques that are typically vulnerable to the high-dimensionality
problem. To address the issue, we propose a method that exploits two well-tested
models: the document-term model and the transaction analysis model. The proposed
method consists of two phases. In the first phase, we reduce the dimensions of
the SNP genotype data by extracting significant SNPs through transformation of
the data in lieu of the document-term model. In the second phase, we discover the
association rules that signify the relations between the SNPs and the traits,
through the application of transactional analysis in the reduced-dimension
genotype data. We validated the discovered rules through literature survey.
Experiments were also carried out using the HGDP panel data provided by the
Foundation Jean Dausset-CEPH, which prove the validity of our new method for
identifying appropriate dimensional reduction and associations of multiple SNPs
and traits. This paper is an extended version of our workshop paper presented in
the 2010 International Workshop on Data Mining for High Throughput Data from
Genome-Wide Association Studies.
PMID- 23155782
TI - Predicting linear B-cell epitopes by using sequence-derived structural and
physicochemical features.
AB - The identification of linear B-cell epitopes is important for developing epitope
based vaccines. Recently, machine learning techniques have been used in the
epitope prediction, but the existing encoding schemes usually neglected valuable
discriminative information. In this paper, we proposed a novel encoding scheme
which combines several groups of sequence-derived structural and physicochemical
features, and support vector machine was used to construct the prediction models.
When applied to the benchmark dataset, our proposed method demonstrated better
results than benchmark methods. Moreover, the study indicated incorporating more
discriminative features may contribute to the higher prediction performance.
PMID- 23155783
TI - [Transgenerational psychotraumatology].
PMID- 23155784
TI - [Intergenerational transmission of trauma--empirical research and family dynamics
approach].
AB - A tendency to pass on traumatic experiences from one generation to the next can
be observed in family systems. This continuity manifests itself very differently,
e. g. in posttraumatic stress disorders, anxiety disorders, mood disorders,
aggressive behavior, social withdrawal or health risk behaviors in the second or
third generation. Besides physiological mechanisms (e. g. levels of cortisol)
psychosocial "mediators" as attachment security, emotional regulation and
availability, parenting style as well as family dynamic processes like family
secrets, communication deviances and resulting disturbances of mentalization,
disturbances of interpersonal boundaries, conflicts of loyalty and delegation are
of relevance. A case example and considerations of resilience processes are given
as well.
PMID- 23155785
TI - [Burden and capability of damaged parents--how refugee children can grow in
exile].
AB - In trauma, dialectical tension arises between the inner perspective of the
traumatized subject and the outside perspective (objective situation), between
environmental stress and the subjective attribution of meaning, as well as
between experience and behaviour. The traumatic process--the subject's endeavour
to comprehend the overwhelming, often inconceivable experience and integrate it
into its concepts of self and world--is understood against the backdrop of these
interacting dimensions. The process phases "emerge from each other, run parallel,
and permeate each other" (Fischer u. Riedesser, 2003). Problems that arise in the
aftermath of trauma are rarely overcome by the victims alone. Attempts to process
and self-heal have a social dimension, and family members are affected by war,
persecution and flight in individual, varying ways. The impacts of violence
experienced by parents from different crisis regions are examined in case studies
with regard to the psychological development of indirectly impacted children
growing up in exile.
PMID- 23155786
TI - [The transgenerational transmission of traumatic experiences of the Second World
War over three generations--a psychoanalytical perspective].
AB - The paper presents some reflections on the transgenerational transmission of
traumatic experiences of war and in particular bombing during Second World War.
These theoretical considerations are based on a case study (family interview)
deriving from the research project "Kriegskindheit im Hamburger Feuersturm"
additionally illustrated and complemented with impressions based on interviews
with three generations in context of the project.
PMID- 23155788
TI - Acute spinal cord injury - the unchanged challenges!
PMID- 23155787
TI - ["Suddenly I was all alone": traumatic experiences of a 12 year old girl during
the "Operation Gomorrha" and its transmission over three generations].
AB - Air strikes on Hamburg in 1943 ("Operation Gomorrha") were a historical turning
point and had a deep impact on both cityscape and history of Hamburg. Little is
known about intraindividual and transgenerational consequences as well as its
interaction with societal and historical processes. Aiming at closing this gap
interviews with witnesses, their children and grandchildren, as well as the whole
family, were conducted in the context of an interdisciplinary research project.
Based on the example of an interview with a at the time of the "Operation
Gomorrha" eleven years old witness, her daughter, and grandson the biographical
localisation of war experiences and transgenerational transmission will be
explained and discussed.
PMID- 23155789
TI - Acute spinal cord injury: managing at the site of impact and addressing reality
gap.
PMID- 23155790
TI - A physicians' approach to a case of acute spinal cord injury.
PMID- 23155791
TI - Pharmacological management of acute spinal cord injury.
PMID- 23155792
TI - Operative management of spinal injuries.
PMID- 23155793
TI - Rehabilitation for spinal cord-injured patients--Looking beyond bladder, bowel
and bed sores.
PMID- 23155794
TI - Stem cell therapy in spinal cord injuries: current concepts.
AB - The list of experimental therapies that have been developed in animal models to
improve functional outcomes after spinal cord injury is extensive. Though
preclinical trials have shown a good potential for cellular therapies in spinal
cord injury, there is no documentary proof as of now that any form of cellular
therapy definitely improves outcome in management of human spinal cord injury.
The adverse effects of many such therapies are well-documented. There is a need
to conduct proper clinical trials. Some early-stage spinal cord injury clinical
trials have recently been done and some have been started. However, some
experimental therapies have been introduced into clinical practice without a
clinical trial being completed. Undue hype by the media and claims by
professionals have a profound psychological effect on the spinal cord injured and
interferes in their rehabilitation. While we know that the future holds a good
promise, this should not prevent patients from aggressively pursuing
rehabilitation since we are not sure when a clinical breakthrough will be
achieved.
PMID- 23155795
TI - Dyspepsia.
PMID- 23155796
TI - Functional dyspepsia: the Indian scenario.
PMID- 23155797
TI - Epidemiology of functional dyspepsia.
AB - Functional dyspepsia (FD) is the most common cause of dyspeptic symptoms. It
refers to a heterogeneous group of symptoms located in the upper abdomen. The
prevalence of dyspepsia is variable in different populations and is related to
the different definitions of dyspepsia as inclusion criterias, variation in
survey population and environmental factors. Epidemiologically some risk factors
have been identified and underlying psychological disturbances have been shown to
be important factors in FD. Age and ethnicity do not appear to be predictive of
dyspepsia. A majority of patients suffering from significant levels of abdominal
pain that interrupt daily activities and treatment remains unsatisfactory in this
chronic condition.
PMID- 23155798
TI - Non-ulcer dyspepsia.
PMID- 23155799
TI - Natural history of functional dyspepsia.
PMID- 23155800
TI - Etiopathogenesis of functional dyspepsia.
PMID- 23155801
TI - Clinical features of functional dyspepsia.
PMID- 23155802
TI - Differential diagnosis in functional dyspepsia.
PMID- 23155803
TI - Management of functional dyspepsia.
PMID- 23155804
TI - Future directions in functional dyspepsia.
PMID- 23155805
TI - India needs a national COPD prevention and control programme.
PMID- 23155806
TI - Newer therapies for chronic obstructive pulmona disease.
PMID- 23155807
TI - COPD: the unrecognized epidemic in India.
PMID- 23155808
TI - Risk factors and pathophysiology of chronic obstructive pulmonary disease (COPD).
PMID- 23155809
TI - Spirometry in chronic obstructive lung disease (COPD).
PMID- 23155810
TI - Management of chronic stable COPD.
PMID- 23155811
TI - Treatment of acute exacerbation of COPD.
PMID- 23155812
TI - Systemic manifestations of COPD.
PMID- 23155813
TI - Pulmonary rehabilitation in COPD.
PMID- 23155814
TI - Smoking cessation programs and other preventive strategies for chronic
obstructive pulmonary disease.
PMID- 23155815
TI - Community acquired pneumonia.
PMID- 23155816
TI - Epidemiology of community acquired pneumonia.
PMID- 23155817
TI - Pathophysiology of community acquired pneumonia.
PMID- 23155818
TI - Community acquired pneumonia: clinical manifestations.
PMID- 23155819
TI - Investigations for pneumonia.
PMID- 23155820
TI - Diagnosis of community acquired pneumonia.
PMID- 23155821
TI - Management of community acquired pneumonia.
PMID- 23155822
TI - Pneumonia: review of guidelines.
PMID- 23155823
TI - Role of vaccines.
PMID- 23155824
TI - Community health nursing.
PMID- 23155825
TI - Preserving health in the Marcellus region.
AB - Community health nurses (CHNs) have an opportunity and responsibility to address
potential environmental health issues related to shale drilling, even in the face
of scientific uncertainty. Potential health impacts to air and water quality
related to shale drilling are addressed within the context of the CHNs role of
educator, case finder, advocate and researcher. Since 2005, an estimated 5,500
unconventional natural gas wells have been drilled in Pennsylvania's Marcellus
Shale (Pennsylvania Department of Environmental Protection [PA DEP], n.d.),
resulting in tremendous controversy throughout the state regarding impacts to
human health and the environment. Although there are numerous anecdotal reports
of illnesses in humans and animals living in drilling areas, there is a notable
lack of peer-reviewed research on the impacts. Research efforts are underway to
study these issues, including a proposed retrospective study of hospital and
clinic data by Geisinger Health System's Weis Center for Research (Begos, 2012).
However, CHNs have the opportunity and the responsibility to help address
potential environmental health issues related to shale drilling, even in the face
of scientific uncertainty. This responsibility is highlighted by the American
Nurses Association's (ANA) (2003, p. 2) adoption of the Precautionary Principle,
which states that "when an activity raises threats of harm to human health or the
environment, precautionary measures should be taken even if some cause and effect
relationships are not fully established scientifically." CHN practice includes
the promotion and preservation of health, and the prevention of disease, as well
as assisting people in their response to illness (Maurer & Smith, 2009). In
Pennsylvania's Marcellus Shale regions, CHNs must assume the critical nursing
roles of educator, case finder, advocate and researcher when addressing the
health needs in shale drilling communities. Unfortunately, CHNs practicing within
these regions may feel unprepared to take on these roles related to
unconventional gas extraction. The following discusses these CHN roles in the
context of environmental health impacts of shale drilling on air and water
quality.
PMID- 23155826
TI - Leading the profession: James Ballinghoff, RN, MSN, MBA, NEA-BC.
PMID- 23155827
TI - Nurse collaboration impacts end of life care.
PMID- 23155828
TI - Nurse-to-Nurse communication in home health.
PMID- 23155829
TI - Changes coming in ANCC advanced practice certification.
PMID- 23155830
TI - Things to know about choosing a nursing school.
PMID- 23155831
TI - Running for elective office: a different form of nursing advocacy.
PMID- 23155832
TI - Are we all under-achievers?
PMID- 23155833
TI - FAQs on continuing education (CE) requirements for registered nurses, licensed
practical nurses, dialysis technicians, community health workers and medication
aides in Ohio.
PMID- 23155834
TI - Novice to expert: clinical ladder programs as a recruitment and retention tool.
PMID- 23155835
TI - If you're not moving, you're standing still.
PMID- 23155836
TI - Addressing the Affordable Care Act.
PMID- 23155837
TI - How old is old?
PMID- 23155838
TI - Health care and behavioral change.
PMID- 23155839
TI - Lost in transition.
PMID- 23155840
TI - Common medical conditions in elderly dental patients. Part one: cardiovascular
implications and management.
PMID- 23155841
TI - Reading...between the lines.
PMID- 23155842
TI - Question: In females being treated with antibiotics, is probiotic use effective
in reducing the incidence of vulvovaginal candidiasis?
PMID- 23155843
TI - Referral pattern for vaginal mesh and graft complications to the University of
Oklahoma Pelvic and Bladder Health Clinic.
AB - OBJECTIVE: To evaluate the referral pattern to a tertiary care center for vaginal
mesh complications following surgeries for pelvic organ support defect. METHODS:
This was a retrospective review of women presenting to our clinic for
complications of vaginal mesh. RESULTS: One hundred thirty three patients were
included in the study. The median age was 58.4 years, median parity was two, and
95.4% were Caucasian. The pattern of referral was as follows: 10% continued care
at the tertiary center where mesh or graft was initially inserted, 18% were
referred by the surgeon who initially implanted the mesh or graft, 71% were
referred from an outside secondary health care provider, and 1% was self
referred. CONCLUSION: The majority of patients presenting to our clinic with mesh
vaginal mesh complications were referred by someone other than the implanting
surgeon.
PMID- 23155844
TI - Interfaces between electronic medical record (EMR/EHR) technology and people in
American medicine: insight, imagination, and relationships in clinical practice.
PMID- 23155845
TI - Looking forward: Where does the emerging field of genomics fit in the health care
delivery system?
PMID- 23155846
TI - Five things physicians and patients should question.
PMID- 23155847
TI - Specialty care.
PMID- 23155848
TI - The Warren Alpert Medical School of Brown University class of 2012.
PMID- 23155849
TI - Warren Alpert Medical School's Doctoring program: a comprehensive, integrated
clinical curriculum.
PMID- 23155850
TI - Curriculum innovation at the Warren Alpert Medical School of Brown University.
PMID- 23155851
TI - Assessing clinical competence of graduating medical students at the Warren Alpert
Medical School of Brown University.
PMID- 23155852
TI - Neighborhood health differentials in Warwick, RI: an analysis of risk factors.
PMID- 23155853
TI - Subungual glomus tumor.
PMID- 23155854
TI - AED's in the dental office.
PMID- 23155855
TI - You have to be the difference.
PMID- 23155856
TI - Health care reform update.
PMID- 23155857
TI - Got yield? 4 asset classes for creating investment income: part 2.
PMID- 23155858
TI - Exposure to airborne ultrafine particles from cooking in Portuguese homes.
AB - Cooking was found to be a main source of submicrometer and ultrafine aerosols
from gas combustion in stoves. Therefore, this study consisted of the
determination of the alveolar deposited surface area due to aerosols resulting
from common domestic cooking activities (boiling fish, vegetables, or pasta, and
frying hamburgers and eggs). The concentration of ultrafine particles during the
cooking events significantly increased from a baseline of 42.7 microm2/cm3
(increased to 72.9 microm2/cm3 due to gas burning) to a maximum of 890.3
microm2/cm3 measured during fish boiling in water and a maximum of 4500
microm2/cm3 during meat frying. This clearly shows that a domestic activity such
as cooking can lead to exposures as high as those of occupational exposure
activities. IMPLICATIONS: The approach of this study considers the determination
of alveolar deposited surface area of aerosols generated from cooking activities,
namely, typical Portuguese dishes. This type of measurement has not been done so
far, in spite of the recognition that cooking activity is a main source of
submicrometer and ultrafine aerosols. The results have shown that the levels of
generated aerosols surpass the outdoor concentrations in a major European town,
which calls for further determinations, contributing to a better assessment of
exposure of individuals to domestic activities such as this one.
PMID- 23155859
TI - Multispecies remote sensing measurements of vehicle emissions on Sherman Way in
Van Nuys, California.
AB - As part of the 2010 Van Nuys tunnel study, researchers from the University of
Denver measured on-road fuel-specific light-duty vehicle emissions from nearly
13,000 vehicles on Sherman Way (0.4 miles west of the tunnel) in Van Nuys,
California, with its multispecies Fuel Efficiency Automobile Test (FEAT) remote
sensor a week ahead of the tunnel measurements. The remote sensing mean gram per
kilogram carbon monoxide (CO), hydrocarbon (HC), and oxide of nitrogen (NO(x))
measurements are 8.9% lower 41% higher, and 24% higher than the tunnel
measurements, respectively. The remote sensing CGO/NO(x) and HC/NO(x) mass ratios
are 28% lower and 20% higher than the comparable tunnel ratios. Comparisons with
the historical tunnel measurements show large reductions in CO, HC, and NO(x)
over the past 23 yr, but little change in the HC/NO(x) mass ratio since 1995. The
fleet CO and HC emissions are increasingly dominated by a few gross emitters,
with more than a third of the total emissions being contributed by less than 1%
of the fleet. An example of this is a 1995 vehicle measured three times with an
average HC emission of 419 g/kg fuel (two-stroke snowmobiles average 475 g/kg
fuel), responsible for 4% of the total HC emissions. The 2008 economic downturn
dramatically reduced the number of new vehicles entering the fleet, leading to an
age increase (> 1 model year) of the Sherman Way fleet that has increased the
fleet's ammonia (NH3) emissions. The mean NH3 levels appear little changed from
previous measurements collected in the Van Nuys tunnel in 1993. Comparisons
between weekday and weekend data show few fleet differences, although the
fraction of light-duty diesel vehicles decreased from the weekday (1.7%) to
Saturday (1.2%) and Sunday (0.6%). IMPLICATIONS: On-road remote sensing emission
measurements of light-duty vehicles on Sherman Way in Van Nuys, California, show
large historical emission reductions for CO and HC emissions despite an older
fleet arising from the 2008 economic downturn. Fleet CO and HC emissions are
increasingly dominated by a few gross emitters, with a single 1995 vehicle
measured being responsible for 4% of the entire fleet's HC emissions. Finding and
repairing and/or scrapping as little as 2% of the fleet would reduce on-road
tailpipe emissions by as much as 50%. Ammonia emissions have locally increased
with the increasing fleet age.
PMID- 23155860
TI - Comparison of the MOVES2010a, MOBILE6.2, and EMFAC2007 mobile source emission
models with on-road traffic tunnel and remote sensing measurements.
AB - The Desert Research Institute conducted an on-road mobile source emission study
at a traffic tunnel in Van Nuys, California, in August 2010 to measure fleet
averaged, fuel-based emission factors. The study also included remote sensing
device (RSD) measurements by the University of Denver of 13,000 vehicles near the
tunnel. The tunnel and RSD fleet-averaged emission factors were compared in blind
fashion with the corresponding modeled factors calculated by ENVIRON
International Corporation using U.S. Environmental Protection Agency's (EPA's)
MOVES2010a (Motor Vehicle Emissions Simulator) and MOBILE6.2 mobile source
emission models, and California Air Resources Board's (CARB's) EMFAC2007
(EMission FACtors) emission model. With some exceptions, the fleet-averaged
tunnel, RSD, and modeled carbon monoxide (CO) and oxide of nitrogen (NO(x))
emission factors were in reasonable agreement (+/- 25%). The nonmethane
hydrocarbon (NMHC) emission factors (specifically the running evaporative
emissions) predicted by MOVES were insensitive to ambient temperature as compared
with the tunnel measurements and the MOBILE- and EMFAC-predicted emission
factors, resulting in underestimation of the measured NMHC/NO(x) ratios at higher
ambient temperatures. Although predicted NMHC/NO(x) ratios are in good agreement
with the measured ratios during cooler sampling periods, the measured NMHC/NO(x)
ratios are 3.1, 1.7, and 1.4 times higher than those predicted by the MOVES,
MOBILE, and EMFAC models, respectively, during high-temperature periods. Although
the MOVES NO(x) emission factors were generally higher than the measured factors,
most differences were not significant considering the variations in the modeled
factors using alternative vehicle operating cycles to represent the driving
conditions in the tunnel. The three models predicted large differences in NO(x)
and particle emissions and in the relative contributions of diesel and gasoline
vehicles to total NO(x) and particulate carbon (TC) emissions in the tunnel.
IMPLICATIONS: Although advances have been made to mobile source emission models
over the past two decades, the evidence that mobile source emissions of carbon
monoxide and hydrocarbons in urban areas were underestimated by as much as a
factor of 2-3 in past inventories underscores the need for on-going verification
of emission inventories. Results suggest that there is an overall increase in
motor vehicle NMHC emissions on hot days that is not fully accounted for by the
emission models. Hot temperatures and concomitant higher ratios of NMHC emissions
relative to NO(x) both contribute to more rapid and efficient formation of ozone.
Also, the ability of EPA's MOVES model to simulate varying vehicle operating
modes places increased importance on the choice of operatingmodes to evaluate
project-level emissions.
PMID- 23155861
TI - Modeling an air pollution episode in northwestern United States: identifying the
effect of nitrogen oxide and volatile organic compound emission changes on air
pollutants formation using direct sensitivity analysis.
AB - Air quality impacts of volatile organic compound (VOC) and nitrogen oxide (NO(x))
emissions from major sources over the northwestern United States are simulated.
The comprehensive nested modeling system comprises three models: Community
Multiscale Air Quality (CMAQ), Weather Research and Forecasting (WRF), and Sparse
Matrix Operator Kernel Emissions (SMOKE). In addition, the decoupled direct
method in three dimensions (DDM-3D) is used to determine the sensitivities of
pollutant concentrations to changes in precursor emissions during a severe smog
episode in July of 2006. The average simulated 8-hr daily maximum O3
concentration is 48.9 ppb, with 1-hr O3 maxima up to 106 ppb (40 km southeast of
Seattle). The average simulated PM2.5 (particulate matter with an aerodynamic
diameter < 2.5 microm) concentration at the measurement sites is 9.06 microg m(
3), which is in good agreement with the observed concentration (8.06 microg m(
3)). In urban areas (i.e., Seattle, Vancouver, etc.), the model predicts that, on
average, a reduction of NO(x) emissions is simulated to lead to an increase in
average 8-hr daily maximum O3 concentrations, and will be most prominent in
Seattle (where the greatest sensitivity is -O.2 ppb per % change of mobile
sources). On the other hand, decreasing NO(x) emissions is simulated to decrease
the 8-hr maximum O3 concentrations in remote and forested areas. Decreased NO(x)
emissions are simulated to slightly increase PM2.5 in major urban areas. In urban
areas, a decrease in VOC emissions will result in a decrease of 8-hr maximum O3
concentrations. The impact of decreased VOC emissions from biogenic, mobile,
nonroad, and area sources on average 8-hr daily maximum O3 concentrations is up
to 0.05 ppb decrease per % of emission change, each. Decreased emissions of VOCs
decrease average PM2.5 concentrations in the entire modeling domain. In major
cities, PM2.5 concentrations are more sensitive to emissions of VOCs from
biogenic sources than other sources of VOCs. These results can be used to
interpret the effectiveness of VOC or NO(x) controls over pollutant
concentrations, especially for localities that may exceed National Ambient Air
Quality Standards (NAAQS). IMPLICATIONS: The effect of NO(x) and VOC controls on
ozone and PM2.5 concentrations in the northwestern United States is examined
using the decoupled direct method in three dimensions (DDM-3D) in a state-of-the
art three-dimensional chemical transport model (CMAQ). NO(x) controls are
predicted to increase PM2.5 and ozone in major urban areas and decrease ozone in
more remote and forested areas. VOC reductions are helpful in reducing ozone and
PM2.5 concentrations in urban areas. Biogenic VOC sources have the largest impact
on O3 and PM2.5 concentrations.
PMID- 23155862
TI - Optimization of a horizontal-flow biofilm reactor for the removal of methane at
low temperatures.
AB - Three pilot-scale, horizontal-flow biofilm reactors (HFBRs 1-3) were used to
treat methane (CH4)-contaminated air to assess the potential of this technology
to manage emissions from agricultural activities, waste and wastewater treatment
facilities, and landfills. The study was conducted over two phases (Phase 1,
lasting 90 days and Phase 2, lasting 45 days). The reactors were operated at 10
degrees C (typical of ambient air and wastewater temperatures in northern
Europe), and were simultaneously dosed with CH4-contaminated air and a synthetic
wastewater (SWW). The influent loading rates to the reactors were 8.6 g CH4/m3/hr
(4.3 g CH4/m2 TPSA/hr; where TPSA is top plan surface area). Despite the low
operating temperatures, an overall average removal of 4.63 g CH4/m3/day was
observed during Phase 2. The maximum removal efficiency (RE) for the trial was
88%. Potential (maximum) rates of methane oxidation were measured and indicated
that biofilm samples taken from various regions in the HFBRs had mostly equal CH4
removal potential. In situ activity rates were dependent on which part of the
reactor samples were obtained. The results indicate the potential of the HFBR, a
simple and robust technology, to biologically treat CH4 emissions. IMPLICATIONS:
The results of this study indicate that the HFBR technology could be effectively
applied to the reduction of greenhouse gas emissions from wastewater treatment
plants and agricultural facilities at lower temperatures common to northern
Europe. This could reduce the carbon footprint of waste treatment and
agricultural livestock facilities. Activity tests indicate that methanotrophic
communities can be supported at these temperatures. Furthermore, these data can
lead to improved reactor design and optimization by allowing conditions to be
engineered to allow for improved removal rates, particularly at lower
temperatures. The technology is simple to construct and operate, and with some
optimization of the liquid phase to improve mass transfer, the HFBR represents a
viable, cost-effective solution for these emissions.
PMID- 23155863
TI - The addition of modified attapulgite reduces the emission of nitrous oxide and
ammonia from aerobically composted chicken manure.
AB - The acceleration of the composting process and the improvement of compost quality
have been explored by evaluating the efficacy of various additives, inoculating
with specific microorganisms and the application of various biosurfactants. The
magnesium-aluminum silicate attapulgite is a low-cost potential composting
additive, but its effects on aerobic composting are unknown. This study
investigated the effects of attapulgite application on compost production and
quality during the aerobic composting of chicken manure. Addition of attapulgite
significantly increased the temperature (p < 0.05) while it reduced compost total
organic carbon (TOC) and seed germination indices (GIs) throughout the process.
Its addition enhanced nitrate concentrations, promoted organic matter
degradation, increased seed germination indices, and accelerated the composting
process. Interestingly, attapulgite addition did not increase the population of
ammonia-oxidizing bacteria. These results suggest that attapulgite is a good
additive for the composting industry. IMPLICATIONS: We investigated the addition
of two forms of attapulgite during aerobic composting of chicken manure to
determine their effects under strict composting environmental parameter control.
Our results provides primary evidence that attapulgite may have potential for
application in the composting industry. All treatments showed no increase within
the first 15 days. However, emissions increased for all treatments within 15-45
days, reaching approximately 6300, 2000, and 4000 mg/m2 from the control,
artifactitious attapulgite, and raw attapulgite treatments, respectively.
PMID- 23155864
TI - Air impacts from three alternatives for producing JP-8 jet fuel.
AB - To increase U.S. petroleum energy independence, the University of Texas at
Arlington (UT Arlington) has developed a direct coal liquefaction process which
uses a hydrogenated solvent and a proprietary catalyst to convert lignite coal to
crude oil. This sweet crude can be refined to form JP-8 military jet fuel, as
well as other end products like gasoline and diesel. This paper presents an
analysis of air pollutants resulting from using UT Arlington's liquefaction
process to produce crude and then JP-8, compared with 2 alternative processes:
conventional crude extraction and refining (CCER), and the Fischer-Tropsch
process. For each of the 3 processes, air pollutant emissions through production
of JP-8 fuel were considered, including emissions from upstream extraction/
production, transportation, and conversion/refining. Air pollutants from the
direct liquefaction process were measured using a LandTEC GEM2000 Plus, Draeger
color detector tubes, OhioLumex RA-915 Light Hg Analyzer, and SRI 8610 gas
chromatograph with thermal conductivity detector. According to the screening
analysis presented here, producing jet fuel from UT Arlington crude results in
lower levels of pollutants compared to international conventional crude
extraction/refining. Compared to US domestic CCER, the UTA process emits lower
levels of CO2-e, NO(x), and Hg, and higher levels of CO and SO2. Emissions from
the UT Arlington process for producing JP-8 are estimated to be lower than for
the Fischer-Tropsch process for all pollutants, with the exception of CO2-e,
which were high for the UT Arlington process due to nitrous oxide emissions from
crude refining. When comparing emissions from conventional lignite combustion to
produce electricity, versus UT Arlington coal liquefaction to make JP-8 and
subsequent JP-8 transport, emissions from the UT Arlington process are estimated
to be lower for all air pollutants, per MJ of power delivered to the end user.
IMPLICATIONS: The United States currently imports two-thirds of its crude oil,
leaving its transportation system especially vulnerable to disruptions in
international crude supplies. At current use rates, U.S. coal reserves (262
billion short tons, including 23 billion short tons lignite) would last 236
years. Accordingly, the University of Texas at Arlington (UT Arlington) has
developed a process that converts lignite to crude oil, at about half the cost of
regular crude. According to the screening analysis presented here, producing jet
fuel from UT Arlington crude generates lower levels of pollutants compared to
international conventional crude extraction/refining (CCER).
PMID- 23155865
TI - Effects of activated carbon surface properties on the adsorption of volatile
organic compounds.
AB - Physical and chemical properties of activated carbon (AC) were analyzed to
investigate the effects of adsorbate properties on AC adsorption performance.
Fixed-bed adsorption experiments were conducted with toluene, acetone, and xylene
as adsorbates. From the results, the adsorption capacities of the three
adsorbates had the following order: xylene > toluene > acetone. The correlation
between experimental data and adsorbate properties was also analyzed. The results
showed that different functional groups corresponding to the properties of
adsorbates influenced the adsorptive properties of AC differently. The adsorption
capacity of AC increased linearly as the molecular weight, dynamic diameter,
boiling point, and density of the adsorbate increased. However, adsorption
capacity decreased as the polarity index and vapor pressure of the adsorbate
increased. For adsorption onto three types of AC, the adsorption energies of the
three adsorbates had the following order: xylene > toluene > acetone.
IMPLICATIONS: This paper focused on the research on adsorption behavior of
activated carbon based on adsorbate properties. Adsorption experiments were
conducted under the same condition while the adsorbates were toluene, acetone,
and xylene, respectively. Correlation analysis between experimental data and
adsorbate properties was conducted. The different groups have different influence
on the adsorptive properties of ACs. The adsorption capacity of activated carbon
increases with the increase of adsorbate molecular weight, dynamic diameter,
boiling point, and density, and that this relationship is linear. The
relationship between adsorption capacity and the polarity index and vapor
pressure of adsorbate shows an opposite trend, and the adsorption capacities and
adsorption energies of three kinds of activated carbon for these three adsorbates
had the following order: xylene > toluene > acetone.
PMID- 23155866
TI - Comparison of the purification performance and microbial community functional
diversity in flow-directional-switching and unidirectional-flow biotrickling
filters.
AB - Because of the characteristics of low operating cost and convenient operation,
the biotrickling filter is extensively researched and used to treat low
concentration waste gas contaminated by volatile organic compounds (VOCs) and
other odors. In this paper, two laboratory-scale biotrickling filters were
constructed and toluene was selected as the sole carbon source, and the effects
of different waste-gas flow configuration patterns on the purification capacity
and the microbial community functional diversity of biotrickling filters were
evaluated. The results indicated that the flow-directional-switching (FDS)
biotrickling filter had better purification performance, and the maximum
elimination capacity reached 480 g x m(-3) x hr(-1), which was 17.1% higher than
conventional unidirectional-flow (UF) biotrickling filter. Comparing the
purification capacities of different sections in two biotrickling filters, the
maximum toluene elimination capacity of section III in FDS system could reach 542
g x m(-3) x hr(-1), which was 2.8 times as great as that in UF system, which
resulted from the difference of elimination capacity in two systems. By analyzing
the metabolic activity of two systems by community-level physiological profiling
(CLPP) with Biolog (Biolog Inc., Hayward, CA) ECO-plate technique, metabolic
activity in three sections of FDS system was higher than that of UF system. The
metabolic activity was the highest in section III of FDS system and 46.8% higher
than that of UF system. Shannon index and McIntosh index of section III in FDS
system were 6.2% and 31.5% higher, respectively, than those of UF system.
IMPLICATIONS: The flow-directional-switching (FDS) biotrickling filter had a
better purification performance than unidirectional-flow (UF) biotrickling filter
at high inlet loadings, because FDS produced a more uniform distribution of
biomass and microbial metabolic capacity along the length of the packed bed
without diminishing activity and removal capacity in the inlet section.
PMID- 23155867
TI - Gas-phase elemental mercury removal in a simulated combustion flue gas using TiO2
with fluorescent light.
AB - A previously proposed technology incorporating TiO2 into common household
fluorescent lighting was further tested for its Hg0 removal capability in a
simulated flue-gas system. The flue gas is simulated by the addition of O2, SO2,
HCl, NO, H2O, and Hg0, which are frequently found in combustion facilities such
as waste incinerators and coal-fired power plants. In the O2 + N2 + Hg0
environment, a Hg0 removal efficiency (etaHg) greater than 95% was achieved.
Despite the tendency for etaHg to decrease with increasing SO2 and HCl, no
significant drop was observed at the tested level (SO2: 5-300 ppm, HCl: 30-120
ppm(v)). In terms of NO and moisture, a significant negative effect on etaHg was
observed for both factors. NO eliminated the OH radical on the TiO2 surface,
whereas water vapor caused either the occupation of active sites available to Hg0
or the reduction of Hg0 by free electron. However, the negative effect of NO was
minimized (etaHg > 90%) by increasing the residence time in the photochemical
reactor. The moisture effect can be avoided by installing a water trap before the
flue gas enters the Hg0 removal system. IMPLICATIONS: This paper reports a novel
technology for a removal of gas-phase elemental mercury (Hg0) from a simulated
flue gas using TiO2-coated glass beads under a low-cost, easily maintainable
household fluorescent light instead of ultraviolet (UV) light. In this study, the
effects of individual chemical species (O2, SO2, HCl, NO, and water vapor) on the
performance of the proposed technology for Hg0 removal are investigated. The
result suggests that the proposed technology can be highly effective, even in
real combustion environments such as waste incinerators and coal-fired power
plants.
PMID- 23155868
TI - Winter and summer PM2.5 chemical compositions in fourteen Chinese cities.
AB - PM2.5 in 14 of China's large cities achieves high concentrations in both winter
and summer with averages > 100 microg m(-3) being common occurrences. A grand
average of 15 microg m(-3) was found for all cities, with a minimum of 27 microg
m(-3) measured at Qingdao during summer and a maximum of 356 microg m(-3) at Xi
'an during winter. Both primary and secondary PM2.5 are important contributors at
all of the cities and during both winter and summer. While ammonium sulfate is a
large contributor during both seasons, ammonium nitrate contributions are much
larger during winter. Lead levels are still high in several cities, reaching an
average of 1.68 microg m(-3) in Xi 'an. High correlations of lead with arsenic
and sulfate concentrations indicate that much of it derives from coal combustion,
rather than leaded fuels, which were phased out by calendar year 2000. Although
limited fugitive dust markers were available, scaling of iron by its ratios in
source profiles shows -20% of PM2.5 deriving from fugitive dust in most of the
cities. Multipollutant control strategies will be needed that address incomplete
combustion of coal and biomass, engine exhaust, and fugitive dust, as well as
sulfur dioxide, oxides of nitrogen, and ammonia gaseous precursors for ammonium
sulfate and ammonium nitrate. IMPLICATIONS: PM2.5 mass and chemical composition
show large contributions from carbon, sulfate, nitrate, ammonium, and fugitive
dust during winter and summer and across fourteen large cities. Multipollutant
control strategies will be needed that address both primary PM2.5 emissions and
gaseous precursors to attain China's recently adopted PM2.5 national air quality
standards.
PMID- 23155870
TI - Regulation. Francis for CQC.
PMID- 23155871
TI - Care Quality Commission. New chief warns cuts threaten quality. Interview by
Sarah Calkin.
PMID- 23155869
TI - Adsorption behavior of toluene on modified 1X molecular sieves.
AB - In this paper, the toluene adsorption/desorption properties of modified 13X
molecular sieves (M-13X) are discussed. M-13X molecular sieves were prepared by
acidic and steam treatments of 13X molecular sieves. The structural parameters of
M-13X were evaluated and compared with those of other molecular sieves (HY, HZSM
5, Cs7NaMOR, and a commercial 13X). The results show that the specific surface
area, average pore diameter and pore volume of M-13X were 414.17 m2/g, 2.98 nm,
and 0.31 mL/g, respectively. The pore size distribution of M-13X was 1.8-3.0 nm.
Because of its larger Si/Al ratio (Si/Al = 6.77), the hydrophobicity of M-13X is
much higher than that of 13X (Si/Al = 1.28), indicating that it is particularly
well suited to toluene control applications. The saturation adsorption capacity
of M-13X was 0.045 g/g for simulated toluene at a temperature of 293 K and a
relative humidity of 50%. The optimal regeneration temperature of M-13X was 473 K
for 120 min with a hot air flow rate of 140 L/min. IMPLICATIONS: The modified 13X
molecular sieves (M-13X) are adsorbents with a high adsorption capacity and great
hydrophobicity, suitable for the treatment of VOCs. The purpose of the present
investigation is to provide a practical guide for their design.
PMID- 23155872
TI - Talking dirty on healthcare waste. Interview by Claire Read.
PMID- 23155873
TI - Justifying health priorities will not be easy.
PMID- 23155874
TI - Doctors' orders.
PMID- 23155875
TI - Performance management. 'Light the fire of enthusiasm'.
PMID- 23155876
TI - Service improvement. Standard bearers.
PMID- 23155877
TI - Foundation trusts. Why governors are the power behind the chairs.
PMID- 23155878
TI - Quality. When patients become leaders.
PMID- 23155879
TI - Survey. Dispensing wisdom.
PMID- 23155880
TI - Legal. What happens after we pull the plug on PCTs?
PMID- 23155881
TI - Public health. Serve up a change that lasts for life.
PMID- 23155882
TI - Health reform: changing the therapeutic order of the nation (one step at a time).
PMID- 23155883
TI - Building on conscious change: AHNA prepares for the role of advocacy.
PMID- 23155884
TI - Holistic nursing and healthcare reform: challenges and opportunities.
PMID- 23155885
TI - Health care reform begins with caring for ourselves.
PMID- 23155886
TI - Patient-Centered Outcomes Research Institute: a response to public outcry for
better use of healthcare dollars.
PMID- 23155887
TI - Art of aromatherapy for end-of-life care.
PMID- 23155888
TI - The happy dental patient.
PMID- 23155890
TI - The human side of dentistry: all in the family.
PMID- 23155889
TI - The battle of the bonds.
PMID- 23155891
TI - Perserverance.
PMID- 23155892
TI - Recruitment and retention of Alaska natives into nursing: elements enabling
educational success.
AB - In response to the underrepresentation of Alaska Native/American Indian nurses,
nursing programs have implemented recruitment and retention efforts to support
undergraduate Alaska Native/American Indian nursing students. The objective of
this project was to provide graduates from the Recruitment and Retention of
Alaska Natives into Nursing (RRANN) program the opportunity to identify program
elements important to achieving academic success, levels of satisfaction, and
make recommendations for future program direction. Findings suggest RRANN
graduates viewed the program as vital to academic success. Recommendations
include utilizing former graduates in recruitment and retention efforts, as
mentors, and extending the program to benefit graduate students.
PMID- 23155893
TI - Improving communication through accent modification: growing the nursing
workforce.
AB - A pilot program was developed to reduce the attrition rate among nursing
students, especially those in ethnic and minority groups. The presence of accents
and dialects among some of these students created communication difficulties
which had the potential to negatively impact both academic success and patient
safety in healthcare settings. Screening processes used to identify students with
reduced speech intelligibility, specific accent modification methods and other
speech improvement lessons implemented to improve overall communication abilities
are described. Clarity of communication improved in all pilot program students.
PMID- 23155894
TI - Faculty and student perceptions of academic incivility in the People's Republic
of China.
AB - This is the second article of a two-part series regarding nursing faculty and
student perceptions of incivility in nursing education in the People's Republic
of China (PRC). Nursing faculty from the United States of America (USA) and the
PRC collaborated to conduct this empirical study. A sample of 382 Chinese nursing
faculty and students responded to 4 open-ended questions on the Incivility in
Nursing Education (INE) Survey. Both groups reported similar perceptions of
uncivil behaviors, contributors to incivility, and ways to address the problem. A
conceptual model for fostering civility in nursing education was adapted to
illustrate the findings.
PMID- 23155895
TI - Bias in the nursing workplace: implications for Latino(a) nurses.
AB - The nursing shortage coupled with health inequities makes it imperative to retain
nurses from diverse backgrounds in the workplace. Since Latinos are the fastest
growing racial/ethnic group in the U.S., the issue is of particular importance.
Thus, the purpose of this study was to measure the prevalence of bias in the
nursing workplace as experienced by Latino(a) nurses. This descriptive study of
Latino(a) nurses measured the prevalence of bias, its relationship to nurse
retention in the nursing workplace, and additional factors in the workplace that
were associated with bias. Results included that Latino(a) nurses both
experienced and witnessed bias on a regular basis, along with negative comments
by peers about their ethnicity. Significant correlations were found between
experiences of bias and the study variables of witnessing bias, perceived levels
of support, and time planning to remain in the workplace. As the nursing shortage
continues and increases in severity, retaining nurses becomes as important as
creating new nurses. Nurse managers, hospital administrators, and nurse educators
must develop strategies to educate staff and promote non-biased interactions
between nurses in the workplace, as well as to support nurses from diverse
backgrounds.
PMID- 23155896
TI - Overview of teaching strategies for cultural competence in nursing students.
AB - Multiple curricular approaches are being used to teach cultural competency to
nursing students in the United States in accordance with accrediting board
standards. As nurse educators are searching for evidence based teaching
practices, this article reviews the most commonly current teaching methods being
used. Although a variety of methods are being implemented, little empirical
evidence exists to suggest any one methodology for teaching cultural competency
for nursing students produces significantly better outcomes. The use of clinical
experiences, standardized patients and immersion experiences have produced the
most favorable results which increase student awareness, knowledge and confidence
in working with ethnically diverse patients.
PMID- 23155897
TI - "Don't allow nursing to surrender its voice".
PMID- 23155898
TI - Trusts hire staff to ensure safety.
PMID- 23155899
TI - "We will be watching the progress on maternity pledges".
PMID- 23155900
TI - "The stage 1 mentor role for new nurses needs questioning".
PMID- 23155901
TI - What are the barriers to good mentoring?
AB - This article reports on a study exploring the barriers to successful mentoring of
pre-registration nursing and midwifery students in practice, and the support
required by mentors. When asked what barriers could affect the quality of
mentoring provided, 70% of the 199 mentors taking part in the study cited lack of
time and 67% cited conflict between the competing demands of being a mentor and
providing patient care. Some 41% of the mentors received very little protected
time from clinical duties to support and assess students. Mentors said they
needed more protected time, help with practice assessment documentation and
regular mentor updates.
PMID- 23155902
TI - Advances in patients' cancer journey.
PMID- 23155903
TI - An inclusive approach to personality disorders.
AB - Personality disorder is one of the most misunderstood of mental health disorders.
Historically, people with this diagnosis have experienced exclusion and rejection
from mainstream mental health services and wider multi-agency services. This
article describes the development of a new strategy to build strong, seamless
links across multi-agency services with the aim of providing timely
interventions, improving patient experience and reducing the likelihood of
transitions to more costly services.
PMID- 23155904
TI - Managing acute painful sickle cell episodes in hospital.
PMID- 23155905
TI - A reappraisal of herbal medicinal products.
AB - Complementary and alternative medicine is increasingly popular, and encompasses a
number of systems and therapies based on diverse theories and practices, such as
homoeopathy, traditional herbalism, reiki, ayurvedic medicine and traditional
Chinese medicine. While many are based on metaphysical concepts for which there
is no sound evidence, for herbal medicines there is a rational, scientific basis
and increasing clinical evidence. This article suggests herbal medicines should
no longer be considered part of CAM, but instead sit alongside conventional
medicines.
PMID- 23155906
TI - Dedicated to nursing.
PMID- 23155907
TI - Driven by seeking out the details.
PMID- 23155908
TI - Pertussis has re-emerged.
PMID- 23155909
TI - Medical humanities--serious academic pursuit or doorway to dilettantism?
PMID- 23155910
TI - Reporting biochemical toxicology to the coroner must be improved.
PMID- 23155911
TI - Concealed pregnancy: prevalence, perinatal measures and socio-demographics.
AB - A target group of women who concealed their pregnancy (n = 43) was compared to an
aged-matched control group (n = 30) that experienced a crisis pregnancy.
Comparisons were also made with a larger dataset (n = 6363) of births in
University Hospital Galway (UHG) (normative group). Data was analysed using the
Chi-square test and the Kolmogorov-Smirnoff two-sample test. The number of women
from the target group that were from a rural background was 28 (65%), compared to
10 (33%) from the control group. The number of women from the target group that
feared a negative parental reaction to the pregnancy was 34 (79%), compared to 12
(40%) from the control group. The birth weight in the target group was 4009 lower
than the normative birth weight. The average age of women who concealed was 8
years lower than the normative age. The prevalence of concealed pregnancy in UHG
was one in every 148 births.
PMID- 23155913
TI - Successful introduction of ring-fenced inpatient surgical beds in a general
hospital setting.
AB - This study aimed to assess the impact of ring-fenced inpatient general surgical
beds on day of surgery (DOS) admission, duration of elective inpatient stay
(DEIS), and cancellation rates over a 6 month period. In June 2010 17 of 60
surgical inpatient beds were decommissioned. The remainder (43) were ring-fenced
for general surgery patients only. Comparative analysis examining admission
rates, cancellation rates, and theatre activity was performed between a reference
period (January-June 2010) and the study period (July-December 2010). Complexity
of all operations was graded according to an index schedule of procedures. There
was no difference between the reference and study periods in volumes of elective
admissions (472 [53.03%] vs. 418 [4797%]) and emergency admissions (928 [50.03%]
vs. 927 [49.97%]). DOS admissions increased 5-fold during the study period (38
[8.1%] vs. 190 [45.5%], P < 0.001). Average duration of elective inpatient stay
reduced from 4.3 days to 3.06 days in the study period (P < 0.001). No difference
was observed in volume of operations performed at all levels of complexity. There
were 78 (58.2%) cancellations during the reference period and 56 (41.8%) during
the study period with patient non-attendance the most common cause for
cancellation in both periods. Ring-fenced surgical beds facilitated higher DOS
admission rates and shorter duration of elective inpatient stay, leading to more
efficient use of hospital resources.
PMID- 23155912
TI - Weaning onto solid foods: some of the challenges.
AB - Weaning--the transition from milk to solid food--influences life-long health.
Dietary challenges during weaning include providing sufficient critical nutrients
such as iron with minimal added sugar and fat and no added salt. This study
assessed the inclusion of iron-containing red meat in infant diets before age one
year, and the Irish commercial baby food environment. Of mothers with an infant
under 30 months of age who were surveyed in shopping centres in Ireland (n195),
82% (n159) reported wanting more weaning information. A quarter (n24) of infants
over age 12 months (n97) received no iron-containing red meat before age one
year. A scan of commercial baby foods in Ireland identified 448 products. While
all complied with baby food legislation, 15% (n69) were intrinsically high in
sugar and fat, or contained added salt. This study indicates the need for
specific guidance on best infant feeding practice in Ireland.
PMID- 23155914
TI - Geriatric medicine in the emergency department.
AB - Studies suggest older adults attending emergency departments(ED) benefit from
specialist geriatric medicine evaluation. Findings from a pilot ED Geriatric
Medicine(GM) liaison service in our 480-bed university hospital are presented.
This is not a randomized controlled trial. Service comprised consultant
geriatrician and senior trainee-led sessions during daytime working hours. Senior
ED personnel selected appropriate patients. GM service also took over ED medical
admissions aged 80, 1 in 9 days from General Internal Medicine(GIM). 49% of 284
patients (83.5 +/- 6.8 years) referred, were discharged from ED with appropriate
follow-up. Inpatient analysis comprised 51% admitted to GIM, GM and specialist
services as per on-call rota and 268 patients taken over from GIM. Patients under
GM had shorter length of stay (p < 0.001). The findings suggest specialty
specific geriatric medicine management of the older adult presenting to ED can
improve service and patient outcomes.
PMID- 23155915
TI - A pain in the neck--medical student attitudes to the Orthopaedic spine.
AB - Considerable deficiencies exist in the teaching of Orthopaedic medicine. This
study aimed (i) to determine if spinal surgery was the Orthopaedic specialty that
students found most difficult, (ii) to appraise attitudes towards teaching of the
spine, and (iii) to suggest ways teaching might be improved. A questionnaire on
Orthopaedic teaching was given to 238 final year medical students in Ireland.
Perceived difficulties with spinal surgery were compared to seven other
Orthopaedic sub-specialties. Suggestions made on how to maximise teaching
potential included 69 (29%) for more tutorials, 43 (18%) for more lectures, 26
(11%) suggested a more structured training programme and 17 (7%) for increased
use of online resources. The spine is one of the least popular Orthopaedic
subspecialties and considerable deficiencies exist in its education.
PMID- 23155916
TI - Pulmonary Mycobacterium szulgai infection.
AB - There has been an increase in the number of pulmonary infections caused by non
tuberculous mycobacteria (NTM) in the non HIV-infected population with a
heightened awareness clinically and in the laboratory of the significance of
these respiratory isolates and newer identification techniques. As far as we are
aware, this is the first case report of pulmonary Mycobacteium szulgai infection
in Ireland.
PMID- 23155917
TI - Laparoscopic Nissen fundoplication post-oesophageal stenting: an unusual case.
AB - Laparoscopic Nissen fundoplication post-oesophageal stenting is uncommon and yet
to be reported. We report the case of a 57-year-old palliative lady who underwent
surgery for symptomatic relief of severe gastrooesophageal reflux post
oesophageal stenting. Surgery was carried out successfully with no complications.
On the evening post-surgery she was able to lie supine for the first time in
months without symptoms of reflux. In conclusion, surgery is still valuable and
may play an important role, even in a palliative setting.
PMID- 23155918
TI - Deep brain stimulation in ireland for Parkinson's disease and essential tremor.
AB - Deep brain stimulation (DBS) is highly effective neurosurgery for idiopathic
Parkinson's disease (IPD), essential tremor (ET) and primary dystonia. DBS
involves stereotactic surgical implantation of a battery-operated stimulator into
deep brain nuclei. Irish patients are referred abroad for DBS and have to travel
repeatedly for pre and post-operative care resulting in stress, anxiety and
hardship. Safe pre and post-operative care of these complex, ageing patients is
compromised by the absence of a DBS service in Ireland. Moreover, both DBS
surgery and the subsequent post-operative care abroad incurs substantial cost to
the state. The Dublin Neurological Institute at the Mater Misericordiae
University Hospital (DNI) is a non-profit institute for the care of patients with
neurological diseases. The DNI developed, in collaboration with the Mater Private
Hospital (MPH) and the Walton Centre, Liverpool, a DBS programme in 2008/2009. We
performed DBS at the Mater Campus on three carefully selected patients from a
cohort of movement disorder patients attending the DNI and continue to provide
pre-operative assessment and post operative care for patients following DBS in
Ireland and abroad.
PMID- 23155919
TI - Improving immunisation uptake across Europe.
PMID- 23155920
TI - Informed consent in refractive eye surgery: learning from patients and the
courts.
AB - Refractive eye laser surgery involves ablation of the cornea using excimer laser
to correct short or long sightedness and thus negate the need for glasses and/or
contact lenses. With the doctrine of informed consent often central to claims of
medical negligence in this area, we examine the attitudes, understanding and
recall of patients to consent for refractive surgery and outline the relevant
law. 102 patients undergoing first time refractive surgery were analysed to
examine their understanding and recall of the consenting process. Only 2 patients
remembered all 5 risks outlined preoperatively, while 11 remembered no risks at
all. 65% of patients consulted the internet to learn more about the operation.
Our study demonstrates that patient understanding and recall remains poor. A
signed consent form is not, of itself a full defence to allegations of uninformed
consent, and the consent process must be comprehensive.
PMID- 23155921
TI - Neonatal meningitis: a diagnostic dilemma.
PMID- 23155922
TI - VACTERL association or VATER syndrome.
PMID- 23155923
TI - Risk of rehospitalisation from an 'off-site' rehabilitation unit for older
adults.
PMID- 23155924
TI - The effect of public deposit of scientific articles on readership.
AB - A longitudinal cohort analysis of 3,499 articles published in 12 physiology
journals reveals a 14% reduction in full text article downloads when they are
made publicly available from the PubMed Central archive. The loss of article
readership from the journal website may weaken the ability of the publisher to
build communities of interest around the research article, impede the
communication of news and events with society members and reduce the perceived
value of the journal to institutional subscribers.
PMID- 23155925
TI - The significance of the Porter Development Fellowship for my career.
PMID- 23155926
TI - The graduate student portfolio: organize and energize your career development.
PMID- 23155927
TI - Common Fund programs: what are they and are you eligible for funding?
PMID- 23155928
TI - Individual account retirement plans: an analysis of the 2010 survey of consumer
finances.
PMID- 23155930
TI - Cardiac surgery inquiry aftermath.
PMID- 23155929
TI - Sources of health insurance and characteristics of the uninsured: analysis of the
March 2012 Current Population Survey.
AB - HEALTH COVERAGE RATE INCREASED, UNINSURED DOWN: The percentage of the nonelderly
population (under age 65) with health insurance coverage increased to 82 percent
in 2011, notable since increases in health insurance coverage have been recorded
in only five years since 1994. EMPLOYMENT-BASED COVERAGE REMAINS DOMINANT SOURCE
OF HEALTH COVERAGE, BUT CONTINUES TO ERODE: Employment-based health benefits
remain the most common form of health coverage in the United States, though it
represents a declining share. In 2011, 58.4 percent of the nonelderly population
had employment-based health benefits, down from the peak of 69.3 percent in 2000,
during the 1994-2011 period. PUBLIC PROGRAM COVERAGE IS EXPANDING: Public program
health coverage expanded as a percentage of the population in 2011, accounting
for 22.5 percent of the nonelderly population. Enrollment in Medicaid and the
State Children's Health Insurance Program (S-CHIP) also increased to a combined
46.9 million in 2011, covering 17.6 percent of the nonelderly population,
significantly above the 10.2 percent level of 1999. INDIVIDUAL COVERAGE STABLE:
The percentage represented by individually purchased health coverage was
unchanged in 2011 and has basically hovered in the 6-7 percent range since 1994.
WHAT TO EXPECT IN 2012: The unemployment rate in 2012 has been about 8 percent
since the beginning of the year, and remains high amidst a still-sluggish
economy. As a result, the nation is likely to see a corresponding erosion of
employment-based health benefits when the data for 2012 are released next year.
Until the economy gains enough strength to have a substantial impact on the labor
market, a rebound in employment-based coverage is unlikely.
PMID- 23155931
TI - Whooping cough case numbers rise across the UK and US.
PMID- 23155932
TI - Annual flu vaccinations for children announced.
PMID- 23155933
TI - Heart surgery reorganise into seven larger centres.
PMID- 23155934
TI - The importance of correctly reading a child's distress.
PMID- 23155935
TI - Value of interaction.
PMID- 23155936
TI - Brain tumours and cancer: insights as a parent and a nurse.
AB - Being told your child has cancer and that her short-term survival is tenuous
probably rates among the most devastating news a parent can ever hear. This
article examines one family's personal journey through the cancer treatment of
their teenage daughter. The author, a registered nurse, also offers insights for
nursing practice about how to deal with patients and their families.
PMID- 23155937
TI - An audit of chemotherapy-induced nausea and vomiting in children.
AB - An audit was conducted of the management of chemotherapy-induced nausea and
vomiting in children and young people in the national Irish paediatric cancer
unit. Over three months, the anti-emetic medication and the incidence of nausea
and vomiting in 50 consecutive patient episodes were recorded among 25 children
receiving chemotherapy for diverse malignancies. Anti-emetic prescription was
found to be unrelated to the emetogenic potential of the chemotherapy received,
so that effectiveness varied. Dexamethasone was used in only one case. Twenty
children did not take any anti-emetics following discharge, although 11
experienced delayed vomiting, evidence-based guidelines were established and now
include anti-emetic prescription that is proportional to the emetogenic potential
of the chemotherapeutic regimen. It is also recommended that staff, patients,
families and carers should receive education about the need for prescription and
use of anti-emetics after discharge.
PMID- 23155938
TI - Early intervention and management of adrenal insufficiency in children.
AB - The endocrine disorder adrenal insufficiency includes inadequate production of
the steroid hormone cortisol. This results in poor physiological responses to
illness, trauma or other stressors and risk of adrenal crisis. Management is
based on administration of hydrocortisone. It is important to avoid under- or
over-treatment and increase the dosage during times of physiological stress. To
reduce morbidity, hospital admissions and mortality, the education and
empowerment of parents and carers, and prompt intervention when necessary are
essential. A steroid therapy card for adrenal insufficiency containing personal
information on a patient's condition was developed for use by families and their
specialist centres.
PMID- 23155939
TI - Training high: a clinical skills initiative for families and staff.
AB - During the past 50 years the care of children and young people who are unwell in
the UK has shifted out of the hospital environment and into the community and has
become more complex, requiring the development among families and care staff of
corresponding clinical skills. The ongoing initiative Training High aims to meet
this need by offering appropriate training programmes to families and
professional carers so they can safely undertake certain procedures. This article
describes the success of one training project in England.
PMID- 23155940
TI - Involving school students in selecting candidates for children's nursing.
AB - This year-long project involved 26 academy school students aged 13-15 years
taking an active role in selecting from candidates for children's nursing places
at the University of the West of England. Meticulous planning, preparation,
debriefing and awareness of safeguarding needs were all needed. Further aspects
relating to increased pressures on academic time, recruitment and preparation of
university student supporters, and project funding, also required attention. Some
candidates reported the inclusion of school students to be challenging; others
found it helpful in clarifying their career aspirations. The project has run for
three years and further evaluations could measure the efficacy of this initiative
to candidate selection. Other institutions may wish to consider adopting this or
a similar approach.
PMID- 23155941
TI - Take the pledge: Online personal health records help RNs, other consumers in
their decision-making.
PMID- 23155943
TI - Reduced Medicare spending could cost more than 750,000 jobs.
PMID- 23155942
TI - Behind the technology: Nurses develop and use e-systems to make patient care,
RNs' working life better.
PMID- 23155944
TI - Health care as a basic human right.
PMID- 23155945
TI - Technology helps to reduce nurses' risk to sharps injuries.
PMID- 23155946
TI - Nurses leading in health care transformation. Interview by Susan Trossman.
PMID- 23155947
TI - APRNs benefit from EHR incentive program.
PMID- 23155948
TI - Cost growth 101 for the physician: what drives the rapidly growing health care
costs?
PMID- 23155949
TI - Women doctors' purses as an unrecognized fomite.
AB - OBJECTIVE: Health care associated infections are serious problems for today's
medical community. It is generally assumed that health care workers come in
contact with pathologic bacteria and unwittingly transfer them to patients either
directly with their hands, or indirectly through some inanimate object. If a
doctor washes his or her hands before seeing a patient and then touches a
colonized object, the benefit of hand washing may have been undone. Previous
studies have identified stethoscopes, neck ties, mobile phones, keyboards, lab
coats, and other commonly worn accessories as potential sources of disease
transmission contributing to health care associated infections. Women doctors'
purses have not previously been studied as a potential source of disease
transmission. This study evaluated whether doctors' purses served as a potential
source of disease transmission. METHODS: We performed a case-control study to
determine if women doctors' purses were colonized more frequently than controls.
Purses were obtained from women doctors who visit a hospital as part of their
clinical responsibilities in the experimental group. Thirteen doctors fit the
criteria of visiting an acute care facility while bringing a purse with them.
Fourteen controls were non-health care women who had not visited a hospital in
the past six months. RESULTS: We observed that nine of 13 doctors' purses were
colonized with bacteria compared with two of 14 controls. CONCLUSIONS: This
statistically significant finding demonstrates that there is a potential for a
doctor's purse to serve as a vector for disease transmission. It is prudent for
women health care workers to be aware that their purses may be a source of
bacterial contamination. We, therefore, recommend that women practitioners use
appropriate infection control measures whenever their purses are in the health
care environment.
PMID- 23155950
TI - How will the delivery of medical care be changing and does the lay public know
enough about it?
PMID- 23155951
TI - Response to Shifting standards of care.
PMID- 23155952
TI - Response to Did I say that? Speech recognition technology.
PMID- 23155953
TI - Psychiatric co-morbidity: revisiting the "mind-body" connection.
PMID- 23155954
TI - Serum lipids, proteins and electrolyte profiles in rats following total body
irradiation.
AB - OBJECTIVE: Serum lipid and electrolyte imbalances are common in critically ill
patients undergoing radiation therapy. Although multiple disease states and
medication may be responsible for the development of these disorders, the aim of
this research is to sequentially document the effect of total body radiation on
body function utilizing the sequential changes in the serum lipids, electrolytes
and protein in rats. METHODS: Serum protein and lipids contents were assessed
using kits while electrolytes were assessed with flame photometry in rats exposed
to total body irradiations of 1.27 Gy/min in cumulative doses to the fourth
irradiation at five-day intervals. RESULTS: Total cholesterol and
triacylglycerols serum levels were significantly reduced by irradiation (p <
0.05). No significant differences between experimental and control groups for HDL
C serum levels were detected. Serum electrolyte concentration remained within the
normal range after each total body irradiation. Sodium, bicarbonate and chloride
were significantly (p < 0.05) higher than control while potassium and creatinine
were significantly reduced after the first irradiation only. Sodium/potassium
ratio was significantly (p < 0.05) elevated. Serum protein was significantly (p <
0.05) elevated with increasing radiation. CONCLUSION: There are subtle but
significant changes in serum lipids, electrolytes and protein after total body
irradiation of normal rats. These variations could be due to non-specific stress
reactions; as such, they are important markers in radiation induced injury
diagnosis.
PMID- 23155955
TI - Elevated ferric, calcium and magnesium ions in the brain induce protein
aggregation in brain mitochondria.
AB - OBJECTIVE: Alzheimer's disease and Parkinson's disease are two of several
neurodegenerative disorders that affect the elderly. Although their aetiology
remains uncertain, studies suggest that elevated aluminium or other metal ions in
the brain directly influence the development of the histological abnormalities
normally associated with these diseases; other investigations suggest that metal
ion-induced-dysfunction of mitochondria might be a critical factor. METHODS: In
this study, the impact of elevated aluminum (Al3+), ferric (Fe3+), calcium (Ca2+)
and magnesium (Mg2+) ions on brain histology and on the protein composition of
brain mitochondria were evaluated. Rabbits were injected intra-cerebrally with
1.4% solutions of either aluminium chloride (AlCl3), ferric chloride (FeCl3),
calcium chloride (CaCl2) or magnesium chloride (MgCl2) and sacrificed 10 days
later RESULTS: Histological analysis revealed that Al3+ but not the other ions
induced neurofibrillary degeneration within the midbrain and medulla.
Alternatively, SDS-PAGE revealed that Fe3+, Ca2+ and Mg2+ but not Al3+ induced
alterations to the distribution of brain mitochondrial proteins. Both Fe3+ and
Ca2+ triggered decreased concentration of three low molecular weight proteins (-7
14 kd) but Ca2+ precipitated their total absence. Both ions led to increased
concentration of a high molecular weight protein (-110 kd). In contrast, Mg2 led
to the total absence of the protein of lowest molecular weight (-7 kd) and
increased concentration of a -36 kd protein. CONCLUSION: These results suggest
that elevation of some metal ions in the brain induces protein aggregation with
the nature of the aggregation being highly ion dependent. The results also point
toward major differences between the histopathological effect of Al3+ and other
ions.
PMID- 23155956
TI - Effect of gabapentin on postoperative pain and operation complications: a
randomized placebo controlled trial.
AB - OBJECTIVE: Prevention and treatment of postoperative pain and operation
complications such as nausea and vomiting are most important concerns in
postoperative care. There are several mechanisms involved in postoperative pain.
Gabapentin is a gamma aminobutyric acid analogue that is known as an
anticonvulsant drug. This drug is tolerated well and has known effects on pain
and anxiety. This study has compared the effect of gabapentin on postoperative
pain, operation complications and haemodynamics. SUBJECTS AND METHODS: This
randomized double blinded placebo controlled clinical trial was conducted on 61
patients divided randomly into two groups (30 as cases and 31 as controls). All
patients had total abdominal hysterectomy. In the first group, the patients got
100 mg gabapentin in the night and 300 mg gabapentin orally (one capsule) two
hours before surgery. The second group got one capsule of multivitamin orally.
Then all patients were subjected to the same anaesthesia protocol and total
abdominal hysterectomy. During the 24 hours after operation, the patients were
assessed according to pain, nausea, vomiting, dizziness, systolic blood pressure
(SBP), diastolic blood pressure (DBP), pulse rate (PR) and morphine use at 1, 6,
12 and 24 hours. RESULTS: Mean age and weight of patients were 45.86 +/- 4.06,
48.16 +/- 4.48, 64.56 +/- 13.29 and 68.8 +/- 12.88 in the study population and
control groups, respectively. Except in the first hour after operation (p =
0.02), there was no significant differences between the two groups in morphine
use. There was no significant correlation between the groups according to
postoperative complications and the haemodynamic parameters (PR, SBP and DBP).
CONCLUSION: Results show that gabapentin can decrease the need for morphine use
in the first hour after operation only and has no significant effect on operation
complications. Thus, we suggest gabapentin for pain management, and not to
decrease opium use.
PMID- 23155957
TI - Adequacy of lymph node harvesting in colorectal cancer management: improving
standards, ensuring quality.
AB - OBJECTIVE: The aim of this study was to determine the adequacy of nodal sampling
in resection specimens for colorectal carcinoma in a Jamaican population.
METHODS: The pathology records of all patients who underwent operation for
colorectal carcinoma at the University Hospital of the West Indies (UHWI) during
the five-year period, 2003-2007, were reviewed. Pertinent clinical and pathologic
data were obtained and analysed. RESULTS: One hundred and ninety-one patients
were identified with M:F ratio of 1.1:1 and a mean age of 66 years. There were
119 (63%) left-sided lesions and 70 (37%) right-sided lesions. Stage T3N0 lesions
were the most common and accounted for 41.1% of cases. The predominant histologic
type was adenocarcinoma (99.5%) with the majority being moderately
differentiated. The mean number of nodes sampled in node-negative cases was 13.8
+/- 9.75 nodes for right-sided lesions and 10.64 +/- 7.25 nodes for left-sided
lesions (p = 0.05, CI 95%). The adequacy of nodal sampling was acceptable in
cases of N0 right-sided carcinomas but was unsatisfactory in cases of N0 left
sided carcinomas. More importantly, however in two cases from the right and 10
cases from the left, two or fewer nodes were harvested. CONCLUSION: This review
suggests the need for re-examination of the adequacy of surgical resection and/or
nodal sampling technique for colorectal cancer resection specimens, given the
importance of nodal status in determining the need for adjuvant therapy. Less
than adequate node sampling should not be accepted by the reporting pathologist
or attending surgeon as this has important prognostic implications.
PMID- 23155958
TI - To study the correlation between carrier status of nasal Staphylococcus aureus in
patients on haemodialysis with hepatitis C, hepatitis B and their
sociodemographic features.
AB - AIM: To study the correlation of nasal Staphylococcus aureus carrier status in
patients on haemodialysis, infected by hepatitis C virus (HCV), hepatitis B virus
(HBV), and their sociodemographic features. SUBJECTS AND METHODS: A survey,
including patients' sociodemographic features, was applied to patients by
physicians in face to face interviews. Medical records regarding their serologic
data were recorded from haemodialysis centres. Nasal swab samples of 2 cm depth
from both nostrils of patients were obtained for nasal culture. Samples were
inoculated in 5% sheep blood agar and incubated in an incubator at a temperature
of 37 degrees C for 24 hours. The results were studied by the same
microbiologist. RESULTS: A total of 185 patients were enrolled in the study.
According to culture results, 14.1% of patients (n = 26) had methicillin
sensitive Staphylococcus aureus (MSSA) and 1.1% (n = 2) had methicillin resistant
Staphylococcus aureus (MRSA). Status of viral hepatitis was 3.8% (n = 8), 10.8%
(n = 20) for HBV and HCV respectively. Forty per cent (n = 8) of patients with
HBV (+) had MSSA carrier status. Statistically significant positive correlation
between MSSA and HCV carrier was detected (r = 0.325, p = 0.001) but not between
HBV carrier and MSSA (p = 0.255). CONCLUSION: In the present study, significant
positivity was detected between MSSA carrier status and HCV in patients on
haemodialysis and who have lived together with < or = 2 family members at home.
Particularly, statistically significant correlation between HCV(+) and MSSA
carrier was observed.
PMID- 23155959
TI - A severe pneumonia due to methicillin resistant staphylococcus aureus clone USA
300: implications of vertical transmission.
AB - Staphylococcus aureus is an important pathogen in both community and healthcare
associated pneumonia. We describe a case of severe pneumonia caused by the
methicillin resistant Staphylococcus aureus (MRSA) clone USA 300 in a 44-year old
post-partum woman and the subsequent vertical transmission of this virulent
organism to her neonate.
PMID- 23155960
TI - Images and diagnoses. Haemorrhage into a pituitary macroadenoma. Hypothalamic
harmatoma.
PMID- 23155961
TI - Psychopathological evaluation of patients requesting cosmetic rhinoplasty: a
review.
AB - OBJECTIVE: The goal of this review is to discuss possible underlying
psychopathological situations in patients requesting surgical cosmetic
rhinoplasty operation and to examine potential problems that might arise.
SUBJECTS AND METHODS: An extensive search was conducted through PubMed, Ambase
and Psychlnfo by using related keywords in English, like "rhinoplasty and
psychiatric comorbidities", "rhinoplasty and psychopathology". RESULTS: Patients
who demand cosmetic rhinoplasty operation appealed to the surgeon since they
wanted to feel better about themselves after the surgery. Indeed, some long-term
studies determined that such a situation can take place at high rates. However,
some studies reported the possibility of serious psychological disorders after
such surgical operations. Studies relating to the analysis of psychopathologic
symptoms are quite limited. Research has shown that psychopathologic evaluation
conducted preoperatively is especially important to identify serious
psychopathologies such as personality disorders and body dysmorphic disorder
(BDD). CONCLUSIONS: Exclusion of patients possessing serious psychopathologies
from operations provides better results in the long term. The lack of sufficient
research in this area necessitates new and comprehensive studies.
PMID- 23155962
TI - Prevalence of toxoplasmosis, cytomegalovirus and rubella IgG antibodies in Hatay
women and children.
AB - OBJECTIVE: Toxoplasmosis, cytomegalovirus and rubella may cause congenital
infections. The aim of this study is to investigate toxoplasmosis,
cytomegalovirus and rubella IgG antibodies in women and children who were
admitted to the Hatay Women and Children Hospital between January 1 and December
31, 2009. METHODS: Levels of IgG antibodies for toxoplasmosis, cytomegalovirus
and rubella established with chemiluminescence immunoassay (Architect i2000,
Abbott, USA) method were evaluated, retrospectively. RESULTS: The results were
obtained from 1103 cases. Seropositivity of IgG antibodies for toxoplasmosis (n =
743), cytomegalovirus (n = 929) and rubella (n = 746) were 59.9%, 98.9% and
93.6%, respectively CONCLUSION: Routine serological screening should be
recommended in women of childbearing age. Seronegative subjects should be
vaccinated for rubella and educated for protection from toxoplasmosis.
PMID- 23155963
TI - Endoscopic carpal tunnel release in Jamaica--seven years experience.
AB - OBJECTIVE: To assess the patient profile and outcome of treatment, by endoscopic
release, of patients with carpal tunnel syndrome. METHODS: A descriptive study
was done using data from two sets of patients who had endoscopic carpal tunnel
release in Jamaica from 2004 to 2006 and 2006 to 2010. The medical records of
patients who had a diagnosis of carpal tunnel syndrome using symptoms, clinical
signs and confirmation by nerve conduction test were reviewed. The data were
analysed using SPSS and Micosoft Excel. RESULTS: A total of 68 patients with 75
cases of carpal tunnel syndrome were done. Fifty-two (76%) of these patients were
females and about 50% were older than 41 years old. There were 61 (90%)
unilateral cases. Of these, the majority of cases affected the right hand. All
patients had improvement in symptoms after one week, required minimal analgesic
use, had good compliance with rehabilitation and returned to work after about two
weeks. There were three cases of pilar tenderness, two cases of transient
paraesthesia in the index finger which resolved after three weeks. There were
three failed cases from the first series which had to be converted to open carpal
tunnel release. The complication rate was 6.7%. No serious complications occurred
in the second series and all were treated successfully without interventional
surgery. The rate of conversion to open release was 4%. CONCLUSION: Carpal tunnel
affects mostly middle aged females and when treatment is done by endoscopic
release, there is a fast resolution of symptoms and early return to work.
PMID- 23155964
TI - Sociodemographic determinants of complicated unsafe abortions in a semi-urban
Nigerian town: a four-year review.
AB - BACKGROUND: Abortions performed by persons lacking the requisite skills or in
environments lacking minimal medical standards or both are considered unsafe. It
is estimated that over 20 million unsafe abortions are performed annually and
about 70 000 women die globally as a result, with the majority occurring in the
developing world. This study aims to determine the sociodemographic factors
involved in complicated unsafe abortions. SUBJECTS AND METHODS: The study is a
four-year retrospective evaluation of all cases of complicated unsafe abortions
managed at the Niger Delta University Teaching Hospital, Okolobiri, Bayelsa
state, Nigeria between January 1, 2007 and December 31, 2010. RESULTS: The
incidence of unsafe complicated abortions over the study period was 4.10% of
total deliveries and contributed 14.0% of gynaecological admissions: 34.92%
occurred in adolescents less than 20 years of age, of which the majority (55.55%)
were secondary school students. There were 55.45% of patients who were
nulliparae, 60.32% were unemployed and 69.80% were unmarried. A total of 87.30%
had never used any form of contraceptive. Abortion mortality rate was 256/100 000
deliveries and the case fatality was 4.76%. It constituted 30.0% of all
gynaecological deaths and 17.64% of maternal deaths during the study period. The
commonest cause of death was septicaemia (66.66%). CONCLUSION: Unfavourable
sociodemographic factors are major determinants of the high incidence of unsafe
abortion in the Niger Delta despite strict abortion laws. Concrete measures must
be put in place to address these, as unsafe abortion and its complications are a
major cause of maternal morbidity and mortality in the environment.
PMID- 23155965
TI - The impact of a no-user-fee policy on the quality of patient care/service
delivery in Jamaica.
AB - This paper is a submission to the Sessional Select Committee on Human Resources
and Social Development by the Medical Association of Jamaica on September 25,
2011, and presented orally by both authors on October 20, 2011. It explores the
impact of the no-user-fee policy on the quality of patient care/service delivery
in Jamaica and makes recommendations for reform.
PMID- 23155966
TI - Prevalence of dentine hypersensitivity among adult patients attending a dental
hospital clinic in Turkey.
AB - OBJECTIVES: The aim of this study is to determine the prevalence of dentine
hypersensitivity (DH) and to examine some associated factors such as the
initiating stimuli among adult patients attending the Restorative Clinic of the
Kirikkale University Dental Faculty, Turkey. METHODS: Questionnaires for 1169
patients, 678 men and 491 women, were completed and necessary clinical
examinations performed during a one-year period and patients who were diagnosed
with DH were questioned further about their occupation and smoking habits.
Patients with at least two different quadrants which had sensitive teeth with
sound exposed cervical dentine on the facial surface, were included in the study.
The amount of cervical lesions, buccal gingival recession and initiating factors
associated with the sensitive teeth were also recorded. RESULTS: Of the 1169
patients examined, 89 were diagnosed as having dentine hypersensitivity, giving a
prevalence of 7.6%. The commonest teeth affected were the upper premolars and the
commonest initiating factor was cold drinks. CONCLUSIONS: The prevalence of
dentine hypersensitivity in a postgraduate clinic in Turkey was 7.6%. The
commonest teeth affected were the upper premolar and the commonest initiating
factor was cold drinks.
PMID- 23155967
TI - Orthodontic treatment need of children in Trinidad and Tobago.
AB - OBJECTIVE: This prospective cross-sectional study was undertaken to determine the
normative and perceived orthodontic treatment needs of children aged 11-12 years
in a Caribbean country, Trinidad and Tobago. METHODS: One author, an experienced
orthodontist, examined 367 children using the Dental Health Component (DHC) of
the Index of Orthodontic Treatment Need (IOTN) to assess the normative need. The
same orthodontist administered the questionnaire to assess the patient's
perceived needs using the Aesthetic Component (AC) of the IOTN and the Oral
Aesthetic Subjective Impact Scale (OASIS). RESULTS: The DHC and the AC of the
IOTN and the OASIS showed respectively that 61.4%, 2.5% and 0.6% of the children
had definite need for orthodontic treatment. The female proportion of the sample
was more than the target population but the perceived need and normative need for
orthodontic treatment did not depend significantly (p < 0.05) on the gender or
ethnicity of the subjects of this study. The perception of need for orthodontic
treatment differed inversely from the normative need and this is seen to be
significant (p < 0.05) when OASIS was used. CONCLUSIONS: Approximately three out
of five children in Trinidad and Tobago have a great (or very great) need for
orthodontic treatment for dental health reasons.
PMID- 23155968
TI - Dental anxiety among patients visiting a dental institute in Faridabad, India.
AB - Despite advances in dentistry, anxiety about dental treatment and the fear of
pain remains widespread among patients and is a significant barrier to dental
treatment. This study would therefore provide information so as to minimize
levels of anxiety and aid in planning stress-free treatment. The cross-sectional
study utilizing a self-reported questionnaire based on Modified Corah's Dental
Anxiety Scale (MDAS) framed in Hindi (local language) was performed on 1032
patients (aged 14-68 years). Around 1004 questionnaires were returned (response
rate--97.3%). Overall, prevalence of dental anxiety was high (50.2%), but severe
anxiety (phobia) was low (4.38%). The prevalence of anxiety was seen mostly in
the 20-30-year age group (37.3%). Anxiety was also seen to be significantly
higher in females (mean - 11.79) than in males [mean - 9.47] (p < 0.0000).
Patients anxious about dental procedures are often more difficult to treat.
Anxious patients should be identified and managed appropriately by
behavioural/pharmacological measures.
PMID- 23155969
TI - Periodontal health knowledge and smoking are associated with periodontal
treatment need according to tooth brushing levels.
AB - OBJECTIVE: The aim of this study is to determine whether periodontal health
knowledge is associated with frequency of tooth brushing and periodontal
treatment need. METHODS: Four hundred and two subjects participated in the study.
Data on sociodemographic variables (age, gender, marital status, income, and
education), general health, smoking behaviour tooth cleaning habits and knowledge
on periodontal health/disease were collected with a questionnaire. Periodontal
treatment need was examined using the Community Periodontal Index of Treatment
Needs (CPITN). According to the CPITN scores, the treatment needs were grouped as
minimum (CPITN = 0), low-level (CPITN = 1-2), or high-level (CPITN = 3-4).
RESULTS: Statistical differences were found between the frequency of tooth
brushing and smoking status, marital status, periodontal health knowledge and
periodontal treatment needs. Gender (females), place of residence (urban areas),
education and periodontal health knowledge had positive relationship with tooth
brushing frequency, while smoking and periodontal treatment need had negative
relationship. When multivariate logistic regression analysis was applied, age,
marriage and poor periodontal knowledge were associated with increased low-level
periodontal treatment needs, and age, marriage and smoking were associated with
increased high-level periodontal treatment need. CONCLUSION: In the limits of
this study, we suggest that gender, smoking habits, marital status, place of
residence, education and periodontal health knowledge are determining factors
related to tooth brushing frequency. Periodontal knowledge and smoking are
associated with periodontal treatment needs.
PMID- 23155970
TI - Calabash pregnancy: a malingering response to infertility complicated by domestic
violence.
AB - This is a case report of a 20-year old para 0+0 who presented with an 11-month
pregnancy. On evaluation, the pregnancy was found to be a fake made-up 'calabash
pregnancy'. There were no pregnancy symptoms and she had just menstruated three
weeks prior to presentation. This was a deliberate event in response to delayed
pregnancy attainment complicated by domestic violence. Domestic violence was in
the form of verbal and physical abuse and later was on a monthly basis
precipitated by onset of her menstrual flow. The patient's age, monogamous union
and the fact that she is an orphan made her vulnerable to domestic violence.
PMID- 23155971
TI - Acute hepatitis C infection with unclear route of transmission.
AB - A 43-year old man acquired acute hepatitis C virus (HCV) infection with unclear
route of transmission. There were no known sexual or other risk factors for HCV
acquisition. Phylogenetic analysis confirmed that the case was infected with
identical genotype 1b strain. After symptomatic treatment for three weeks, the
HCV was spontaneously cleared and liver function recovered.
PMID- 23155972
TI - Simultaneous rupture of bilateral quadriceps tendon and rotator cuff tear: a case
report.
AB - This is a case report of a patient who sustained both a bilateral quadriceps
tendon rupture and a complete rotator cuff tear. Overuse is a known risk factor
for rotator cuff tears, but this case suggests that it can also be a risk factor
for quadriceps tendon rupture.
PMID- 23155973
TI - A report summarizing health problems in everyday life in Tokyo: the importance of
discussion from various perspectives.
PMID- 23155974
TI - Twenty-four hour trauma team at the University Hospital of the West Indies,
Kingston, Jamaica--the time is now.
PMID- 23155975
TI - The effect of serum magnesium levels and serum endothelin-1 levels on bone
mineral density in protein energy malnutrition.
AB - An inadequate and imbalanced intake of protein and energy results in protein
energy malnutrition (PEM). It is known that bone mineral density and serum
magnesium levels are low in malnourished children. However, the roles of serum
magnesium and endothelin-1 (ET-1) levels in the pathophysiology of bone
mineralization are obscure. Thus, the relationships between serum magnesium and
ET-1 levels and the changes in bone mineral density were investigated in this
study. There was a total of 32 subjects, 25 of them had PEM and seven were
controls. While mean serum ET-1 levels of the children with kwashiorkor and
marasmus showed no statistically significant difference, mean serum ET-1 levels
of both groups were significantly higher than that of the control group. Serum
magnesium levels were lower than normal value in 9 (36%) of 25 malnourished
children. Malnourished children included in this study were divided into two
subgroups according to their serum magnesium levels. While mean serum ET-1 levels
in the group with low magnesium levels were significantly higher than that of the
group with normal magnesium levels (p < 0.05), mean bone mineral density and bone
mineral content levels were significantly lower (p < 0.05). In conclusion, many
factors play a role in the pathophysiology of changes in bone mineral density in
malnutrition. Our study suggested that lower magnesium levels and higher ET-1
levels might be important factors in changes of bone mineral density in
malnutrition. We recommend that the malnourished patients, especially with
hypomagnesaemia, should be treated with magnesium early.
PMID- 23155976
TI - Family history of diabetes and parental consanguinity: important risk for
impaired fasting glucose in south east Asians.
AB - OBJECTIVE: Offsprings of type 2 diabetics have increased risk of metabolic
disturbances. The aim of the study is to assess the potential effect of family
history of type 2 diabetes (FHD) and parental consanguinity on fasting plasma
glucose (FPG) levels. SUBJECTS AND METHODS: Non-diabetic offsprings of one or
both parents with type 2 diabetes and healthy controls of comparable age, without
a FHD were the subjects of this study. Family history of type 2 diabetes was
defined by the presence of type 2 diabetes in one or both parents of the subject.
Consanguinity was defined as history of marriage with a first cousin. Fasting
plasma glucose levels were determined in cases and controls. RESULTS:
Impairedfasting glucose (IFG) was identified in 42% of subjects with FHD and in
14% without FHD. We found a strong independent association of FHD with impaired
fasting glucose in both males and females by logistic regression analysis after
adjusting the data for age, gender and body mass index (BMI). Parental
consanguinity modifies the effect of FHD on IFG. CONCLUSION: We concluded that
family history of diabetes and parental history of consanguinity determine the
risk for impaired fasting glucose in this study population.
PMID- 23155977
TI - The role of pre-induction ketamine in the management of postoperative pain in
patients undergoing elective gynaecological surgery at the University Hospital of
the West Indies.
AB - OBJECTIVES: To determine if a single preoperative dose of ketamine hydrochloride
reduces the narcotic analgesic requirements and/or pain scores reported by
patients in the first 24 hours postoperatively. METHODS: A single-centred,
prospective, case-control study was conducted on 84 patients aged 18-65 years,
American Society of Anaesthesiologists (ASA) I and II, undergoing elective
gynaecological procedures at the University Hospital of the West Indies (UHWI).
Patients were randomly assigned to one of two treatment groups: (a) ketamine
group, where patients received intravenous ketamine 0.15 mg/kg pre-induction of
anaesthesia; and (b) placebo group, patients received normal saline. The
anaesthetic technique was standardized. Postoperatively, patients were
interviewed at 15-minute intervals for the first hour then at 2, 4, 6, and 24
hours to determine their pain scores and any side effects. Timing and dose of
opioid analgesics were also recorded. RESULTS: The mean cumulative morphine dose
over the first 24 hours postoperatively was 29.6 +/- 10.8 mg for the ketamine
group and 31.9 +/- 11.2 mg for the placebo group (p = 0.324). There was also no
significant difference in pain intensity measured by the visual analogue scale
(VAS) between the groups. Patient age and the type of surgery performed were not
found to influence pain intensity. The most common adverse effects were nausea
and vomiting (32.5%), dizziness (42.2%), drowsiness and sedation (45.8%) with no
significant difference between groups. Both groups had an average in-hospital
stay of three days postoperatively, however, the patients in the ketamine group
reported higher satisfaction scores than those in the placebo group (p = 0.039).
CONCLUSION: Despite no significant reduction in postoperative narcotic
requirements or pain intensity, more patients who received ketamine reported
higher levels of satisfaction with their pain management.
PMID- 23155978
TI - Correlation of cataract with serum lipids, glucose and antioxidant activities: a
case-control study.
AB - OBJECTIVE: The aim of this study is to evaluate the relationship between cataract
development and serum lipids, glucose as well as antioxidants in a case-control
study. METHODS: Ninety patients with cataract and 90 age- and sex-matched healthy
controls were investigated. Lipid profiles including triglyceride (Tg), total
serum cholesterol (Chol) and cholesterol content in high-density lipoproteins
(HDL chol) and low-density lipoproteins (LDL chol) as well as fasting glucose
(FBS) were measured for all subjects. Plasma oxidative stress as thiobarbituric
acid-reactive substances (TBARS) and the status of antioxidants were studied as
ferric reducing/antioxidant power (FRAP) and thiol substance assay. RESULTS: A
higher prevalence of abnormal FBS (8.9 vs. 1.1%), Tg (26.7 vs. 8.9%) and Chol
(54.4 vs. 30%) was found in cataract patients than the control group (p < 0.05).
Plasma Tg (p = 0.02), Chol (p = 0.001) and LDL chol (p = 0.04) were significantly
higher in the cataract group than in the control group. Likewise TBARS (p = 0.05)
as the level of oxidative stress was significantly higher in the case group, and
FRAP (p = 0.03) and thiol (p = 0.02) assays as the antioxidant activity was
significantly lower among cataract patients. CONCLUSION: This study has shown
that hypercholesterolaemia, hypertriglyceridaemia, high LDL chol and high FBS are
associated with cataract. Also lower plasma antioxidant levels and higher levels
of oxidative stress were seen in cataract patients than healthy controls. These
findings indicate a need for health promotional activities aimed at controlling
these preventable factors among high risk populations.
PMID- 23155979
TI - Expression of low molecular weight proteins in patients with leukaemia.
AB - The current study is conducted to observe the differences in the level of low
molecular weight proteins in the sera of patients with leukaemia in comparison to
healthy subjects (control group). The sera of patients with leukaemia showed 15
peaks in the densitometric curve in comparison to the seven peaks of the
controls. The peaks in the experimental samples that coincide with those in the
control were of 134.14, 113.15, 76.06, 63.25, 48.07, 22.85 and 16.47 kDa
molecular weights, respectively. Most of the new peaks appeared between the
proteins of molecular weight 36-29 kDa in the experimental groups. Mean density
of the 134.14 kDa protein band showed an increase in the protein in experimental
groups I and II only whereas 113.15 and 22.85 kDa protein were increased in all
experimental groups of patients with leukaemia. The expression of 76.06 and 63.25
kDa protein fraction was downregulated in the patients with leukaemia. A decline
in the level of the protein of 48.07 kDa was observed in patients with leukaemia
except in group I. Unlike the other protein fractions, the level of the protein
of 16.47 kDa was significantly (p < 0.05) increased with a maximum density in
group II. Intergroup experimental) comparison revealed an increasing pattern of
95.44 and 89.21 kDa with maximum level in group III sera. However the protein
fractions of 38.07 and 34.94 kDa varied in the serum with maximum density in
Group IV Protein fractions of 32.92 and 31.24 kDa were expressed in all age
groups of patients with leukaemia with a maximum density in group III whereas the
percentage densities of 14.42 and 13.56 kDa protein were quite different. This
preliminary study will provide a basis to study the role of different proteins in
patients with leukaemia.
PMID- 23155980
TI - Comparison of urine analysis using manual and sedimentation methods.
AB - OBJECTIVE: Microscopic examination of urine sediment is an essential part in the
evaluation of renal and urinary tract diseases. Traditionally, urine sediments
are assessed by microscopic examination of centrifuged urine. However the current
method used by the Georgetown Public Hospital Corporation Medical Laboratory
involves uncentrifuged urine. To encourage high level of care, the results
provided to the physician must be accurate and reliable for proper diagnosis. The
aim of this study is to determine whether the centrifuge method is more
clinically significant than the uncentrifuged method. METHODS: In this study, a
comparison between the results obtained from centrifuged and uncentrifuged
methods were performed. A total of 167 urine samples were randomly collected and
analysed during the period April-May 2010 at the Medical Laboratory, Georgetown
Public Hospital Corporation. The urine samples were first analysed
microscopically by the uncentrifuged, and then by the centrifuged method. The
results obtained from both methods were recorded in a log book. These results
were then entered into a database created in Microsoft Excel, and analysed for
differences and similarities using this application. Analysis was further done in
SPSS software to compare the results using Pearson ' correlation. RESULTS: When
compared using Pearson's correlation coefficient analysis, both methods showed a
good correlation between urinary sediments with the exception of white bloods
cells. The centrifuged method had a slightly higher identification rate for all
of the parameters. CONCLUSIONS: There is substantial agreement between the
centrifuged and uncentrifuged methods. However the uncentrifuged method provides
for a rapid turnaround time.
PMID- 23155981
TI - Management of breast abscesses in Jamaican women is there need for a paradigm
shift?
AB - A paradigm shift from operative to non-operative management of breast abscesses
has occurred in surgical centres worldwide. The recent experience in managing
these patients at the University Hospital of the West Indies (UHWI) was examined.
Data were obtained retrospectively from dockets retrieved from the UHWI medical
records department, and were analysed using the SPSS version 11.0 software
package for Windows. Seventy-seven patients with breast abscesses presented
during the 66-month study period, but complete data were unavailable for
seventeen cases. The mean age of the remaining sixty patients was 32 years. There
was one male patient. There were no cases of bilateral disease, and the majority
was right-sided. Mean white blood cell count at presentation was mildly elevated
at 11.9 x 10(9)/L, and had no relationship to method of management or length of
stay. There were two cases treated with aspiration and antibiotics only. All
other cases were treated with incision and drainage. Culture results were
available in forty-four cases, and in 80%, Staphylococcus aureus was identified,
with one case of methicillin resistant Staphylococcus aureus. The mean delay to
the operating theatre was one day after presentation and the mean length of stay
was 4.5 days. Seventeen patients had a 'non-cosmetic' incision. The traditional
management of breast abscess provides challenges in terms of delay to the
operating theatre and prolonged hospital stays. There is increased expense, as
well as loss of productive work hours, associated with this line of treatment.
Non-operative management has not traditionally been undertaken in our
institution, but it is documented elsewhere to be safe, practical, and results in
improved cosmetic outcomes. Prospective protocol-based trials are necessary to
identify the patients most suitable for this line of management in a setting with
limited resources.
PMID- 23155982
TI - Establishing the Jamaica lupus registry: report of patients with systemic lupus
erythematosus attending a major referral hospital in Jamaica.
AB - BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disorder
characterized by multisystem microvascular inflammation with the generation of
autoantibodies. There are reports on demographic data and clinical manifestation
of lupus in the United States of America and some other developed countries.
There is a single study that has reported on the clinical and immunological
features of SLE patients in Jamaica and another that reported that the prevalence
of SLE in Jamaica was 5-17/100,000 in 1979. METHOD: A Jamaican lupus registry was
established in 2008 at the Department of Medicine, The University of the West
Indies. Data were collected using patient records and interview of patients
fulfilling the American College of Rheumatology revised diagnostic criteria for
SLE. Information on demographics, presence of diagnostic criteria for SLE,
presence of complications and other clinical parameters were collected. RESULTS:
There were a total of 107 patients that met the criteria for diagnosis of SLE at
the referral centre, 96.3% of them female. Positive ANA (90.7%), arthritis
(70.0%), malar rash (53.5%) and a positive dsDNA (40.1%) were the more frequent
manifestations and diagnostic indices of the disease. Up to 41.7% of the SLE
population suffered some form of complication. CONCLUSIONS: The initiation of a
lupus registry has allowed for reporting ofpreliminary demographic, clinical and
serological data and identifying of disease burden.
PMID- 23155983
TI - The establishment of an intracranial tumour registry at the University Hospital
of the West Indies.
AB - In March 2010, the first intracranial tumour registry (ITR) in the English
speaking Caribbean was started at the University Hospital of the West Indies
(UHWI). This was deemed necessary as the already established Jamaica Cancer
Registry only reports on malignant brain tumours. The ITR will collect data on
all prospective intracranial tumours, benign and malignant, which are diagnosed
histologically at the UHWI. Retrospective information dating back five years was
also collected. Data collected so far reveal that between the years 2006 to 2010,
a total of 317 cases were entered into the database. Of these, only 45 cases were
considered eligible. The issues surrounding this discrepancy are discussed in
this paper along with the many challenges experienced in the establishment of the
ITR. From these experiences, the authors have also put forward several
recommendations that may be useful to other researchers who wish to implement
similar systems.
PMID- 23155984
TI - The impact of the healthcare system in Barbados (provision of health insurance
and the benefit service scheme) on the use of herbal remedies by Christian
churchgoers.
AB - AIM: To determine the impact of health insurance and the government's Benefit
Service Scheme, a system that provides free drugs to treat mostly chronic
illnesses to persons aged 16 to 65 years, on the use of herbal remedies by
Christian churchgoers in Barbados. METHODS: The eleven parishes of Barbados were
sampled over a six-week period using a survey instrument developed and tested
over a four-week period prior to administration. Persons were asked to
participate and after written informed consent, they were interviewed by the
research team. The data were analysed by the use of IBM SPSS version 19. The data
were all nominal, so descriptive statistics including counts, the frequencies,
odds ratios and percentages were calculated. RESULTS: More than half of the
participants (59.2%) were female, a little less than a third (29.9%) were male,
and one tenth of the participants (10.9%) did not indicate their gender The
majority of the participants were between the ages of 41 and 70 years, with the
age range of 51-60 years comprising 26.1% of the sample interviewed. Almost all
of the participants were born in Barbados (92.5%). Approximately 33% of the
respondents indicated that they used herbal remedies to treat various ailments
including chronic conditions. The odds ratio of persons using herbal remedies and
having health insurance to persons not using herbal remedies and having health
insurance is 1.01 (95% CI 0.621, 1.632). There was an increase in the numbers of
respondents using herbal remedies as age increased. This trend continued until
the age group 71-80 years which showed a reduction in the use of herbal remedies,
32.6% of respondents compared with 38.3% of respondents in the 61-70-year
category. CONCLUSIONS: The data demonstrated that only a third of the study
population is using herbal remedies for ailments. Health insurance was not an
indicator neither did it influence the use of herbal remedies by respondents. The
use of herbal remedies may not be associated with affluence. The reduction in the
use of herbal remedies in the age group 71-80 years could be due to primarily a
lower response rate from this age group, and secondarily due to the Benefit
Service Scheme offering free medication to persons who have passed the age of 65
years.
PMID- 23155985
TI - From cannabis to the endocannabinoid system: refocussing attention on potential
clinical benefits.
AB - Cannabis sativa is one of the oldest herbal remedies known to man. Over the past
four thousand years, it has been used for the treatment of numerous diseases but
due to its psychoactive properties, its current medicinal usage is highly
restricted. In this review, we seek to highlight advances made over the last
forty years in the understanding of the mechanisms responsible for the effects of
cannabis on the human body and how these can potentially be utilized in clinical
practice. During this time, the primary active ingredients in cannabis have been
isolated, specific cannabinoid receptors have been discovered and at least five
endogenous cannabinoid neurotransmitters (endocannabinoids) have been identified.
Together, these form the framework of a complex endocannabinoid signalling system
that has widespread distribution in the body and plays a role in regulating
numerous physiological processes within the body. Cannabinoid ligands are
therefore thought to display considerable therapeutic potential and the drive to
develop compounds that can be targeted to specific neuronal systems at low enough
doses so as to eliminate cognitive side effects remains the 'holy grail' of
endocannabinoid research.
PMID- 23155986
TI - Preference of patient information leaflets over standard drug monographs by
patients prescribed hydrochlorothiazide, nifedipine and enalapril.
AB - Standard drug monographs (SDMs) have been described as deficient in providing
information in a manner simplified enough for patient reading. The aim of this
study was to design patient information leaflets for hydrochlorothiazide,
nifedipine and enalapril with content indicated by patients as relevant and to
evaluate them against the SDM. Patient information leaflet (PIL) for each drug
was designed to contain information on name, use of drug, how it works, how it is
to be taken, common side effects, storage, missed dose action, things to avoid
and when to contact the physician. Appropriateness was assessed by 10 practising
pharmacists. For each drug, 40 patients were recruited, of which 20 were given
SDM and 20 PIL. The knowledge of each participant was examined before and after
exposure to SDM or PIL, as well as opinion on ease of reading and attractiveness
using Pearson s Chi-square analysis. The results showed that both SDM and PIL
improved knowledge of common side effects when compared with responses before
exposure (chi2 = 24.26 for SDM and 27.64 for PIL, p < 0.001) with no difference
between the groups. Respondents receiving PILs were better able to recall "things
to avoid" after exposure to PIL (chi2 =10.85, p < 0.001). After exposure to SDM
or PIL, the respondents who received PIL were more aware of when to contact the
physician, compared to the SDM group (chi2 = 8.41, p < 0.01). When compared with
SDM, respondents receiving PIL were more likely to indicate that PIL was easy to
read (chi2 = 20.00, p < 0.001), attractive (chi2 = 12.45, p < 0.001) and they
were more likely to recommend distribution of their reading material to other
patients (chi2 = 22.11, p < 0.001). We conclude that there is benefit in
designing information leaflets that simplify language and medication information
contained in SDMs, including better understanding of precautions to take while on
medication and when to consult physicians.
PMID- 23155987
TI - The origin and future of offshore medical schools in the Caribbean.
AB - The Flexner Report of 1910 concluded that there were too many medical schools in
the United States of America (U.S.A.). In the wake of this conclusion, Flexner
recommended higher admission and graduation standards for medical schools, the
expected impact being fewer medical schools and graduates. One unintended
consequence of this recommendation was a male-only policy by some universities to
accommodate the smaller numbers of males. There were privately owned medical
schools, unaffiliated to any college or universities which were run primarily for
profit. Degrees were usually obtained after only two years of study and
laboratory and dissection exercises were not part of the training. The adoption
of Flexner's recommendation resulted in medical education becoming more
expensive; it also created opportunities for persons without the financial means
or the matriculation requirements to find alternative training programmes among
those "medical schools" which did not adopt Flexner's recommendations. This paper
traces the further development of these "medical schools" to facilitate the need
for more doctors in the context of global maldistribution of doctors which has
resulted in many medically underserved areas, more so in developing countries
(1).
PMID- 23155988
TI - Nutritional markers in patients undergoing chronic haemodialysis in Jamaica.
AB - OBJECTIVES: The main objective of the study is to assess the nutritional status
in patients on chronic haemodialysis in Jamaica using the Subjective Global
Assessment tool and to correlate this with measured serum nutritional biomarkers,
and also to identify nutritional biomarkers that can be used to assess
nutritional status of patients with end-stage renal disease (ESRD). SUBJECT AND
METHODS: Two hundred and nine consecutive patients on haemodialysis were selected
from dialysis centres in Kingston, the capital of Jamaica, St. Catherine and
Manchester Jamaica. The nutritional status of each participant was assessed using
the Subjective Global Assessment tool in an interview performed by the
researcher. Serum albumin, blood urea nitrogen and creatinine, highly sensitive
complement reactive protein (hsCRP) and total fasting cholesterol were determined
from a single serum sample. Only patients with ESRD were selected. Patients with
acute renal failure or those with ESRD who were admitted in the previous two
weeks were excluded from the study. Informed consent was obtained prior to
interview and obtaining blood samples. RESULTS: Of the total participants, 54.5%
(n=114) were male and 45.5% (n=95) female. The mean age for males was 51.9 years
and females 47.6 years. Diabetes was documented as the most common cause of
chronic renal disease and was found in 29.7%, hypertension in 24.4% and chronic
glomerulonephritis in 22% of the participants. Approximately 80% of the study
population had moderate malnutrition. There was a significant association between
moderate malnutrition and a diagnosis of ESRD secondary to diabetes mellitus, p =
0.03. Being on haemodialysis for < or = six months was significantly associated
with moderate malnutrition p = 0.002. Also associated with moderate malnutrition
were presence of an arteriovenous (AV) fistula (p = 0.01), serum albumin of < 40
g/L (OR 3.68, p = 0.001), pre-dialysis creatinine of <880 micromol/L (p = 0.02)
and cholesterol < 3.9 mmol/L (p = 0.04). Highly sensitive complement reactive
protein levels of >10 mg/L was associated with moderate malnutrition, though
statistical significance was not met (p = 0.39). CONCLUSION: Factors associated
with malnutrition in patients on dialysis were having ESRD secondary to diabetes
mellitus, dialysis duration for < or = six months, low serum albumin, pre
dialysis serum creatinine of 880 micromol/L, low total cholesterol and presence
of AV fistula access.
PMID- 23155989
TI - Living donor kidney transplantation: the donor profile in Trinidad and Tobago.
AB - OBJECTIVE: The National Organ Transplant Unit (NOTU) of Trinidad and Tobago,
first implemented in January 2006, was mandated to facilitate renal and corneal
transplantation. Since then, 60 transplants have been performed utilizing living
kidney donors. The aim of this study is to ascertain the typical donor profile
and to highlight the safety involved with live kidney donation. SUBJECTS AND
METHODS: This descriptive study utilized the medical records of 60 consecutive
live kidney donors between the period January 2006 and May 2010. Donor
information was recorded on Microsoft Excel spreadsheets and analysed using the
Statistical Package for Social Sciences 12.0. RESULTS: Among the 60 donors, males
and females were in equal proportions with a mean age of 35.0 (+/- 10.7) years; a
mean body mass index (BMI) of 25.8 (+/- 4.2) kg/m2 and 48.3% were of East Indian
decent. The majority of donors were related to the recipient (71.7%). At
donation, the mean creatinine was 84.9 (+/- 17.7) micromol/L, average urine
creatinine clearance, 1.83 (+/- 0.53) mL/s and mean 24 hour urine protein, 141.8
(+/- 78.6) mg. There was a significant association between the BMI at donation
and proteinuria one year after donation (p = 0.043). The average hospital stay
was 5.0 (+/- 0.95) days with minimal postoperative complications. CONCLUSION: The
typical live kidney donor in Trinidad and Tobago is a 35-year-old, slightly
overweight male or female who is usually of East Indian decent, donating a kidney
to a relative. Living kidney donation in this transplant unit is safe with
minimal short-term complications.
PMID- 23155990
TI - Report and viewpoint on the Vaccine Safety Conference, Tryall Club, Jamaica,
January 3-7, 2011: cautionary tales and implications for the Caribbean.
AB - This paper represents information obtained from a recent conference on
vaccination safety and policy: Vaccine Safety: Evaluating the Science Conference,
Tryall Club, Jamaica, January 3-7, 2011 and the author's viewpoint on the same.
The first section represents a synopsis of recorded information and the second
the author's view of Caribbean concerns related to the recorded information.
PMID- 23155991
TI - Prosthetic reconstruction after surgical resection of fibrous dysplasia of the
maxillary and palatine bone.
AB - Fibrous dysplasia is a rare disorder of the bone. It is seen in two main forms of
presentation: monostotic and the polyostotic. A case of monostotic fibrous
dysplasia of the maxillary and palatine bones in a 22-year old man who received
prosthetic reconstruction is presented with a review of the literature.
PMID- 23155992
TI - A patient experiencing pseudoseizures: a case report.
AB - Pseudoseizures are a relatively complex problem of unknown aetiology and
prognosis. They can at times resemble genuine seizure attacks but they have no
abnormal electroencephalograpic (EEG) activity. Understanding the patient's
unique psychological background appears to be fundamental in managing seizure
frequency. Pseudoseizures can be disruptive to a person's lifestyle, limiting
their ability to function and progress in society, particularly when it comes to
employment or social interaction. The case discussed involves a 59-year-old man
who presents with what is believed to be seizure-related activity but through the
course of clinical evaluation, this turned out to be pseudoseizures.
PMID- 23155993
TI - Sjogren's syndrome: a case report and review of the literature.
AB - The manifestations and complications of Sjogren's syndrome are important to know,
and dentists can play an important role in the detection of this disease. This
report highlights such a case.
PMID- 23155994
TI - Train your people to take others' perspectives.
PMID- 23155995
TI - The art of developing truly global leaders.
PMID- 23155996
TI - Anniversaries are not to be wasted.
PMID- 23155997
TI - Accelerate!
AB - The old ways of setting and implementing strategy are failing us, writes the
author of Leading Change, in part because we can no longer keep up with the pace
of change. Organizational leaders are torn between trying to stay ahead of
increasingly fierce competition and needing to deliver this year's results.
Although traditional hierarchies and managerial processes--the components of a
company's "operating system"--can meet the daily demands of running an
enterprise, they are rarely equipped to identify important hazards quickly,
formulate creative strategic initiatives nimbly, and implement them speedily. The
solution Kotter offers is a second system--an agile, networklike structure--that
operates in concert with the first to create a dual operating system. In such a
system the hierarchy can hand off the pursuit of big strategic initiatives to the
strategy network, freeing itself to focus on incremental changes to improve
efficiency. The network is populated by employees from all levels of the
organization, giving it organizational knowledge, relationships, credibility, and
influence. It can Liberate information from silos with ease. It has a dynamic
structure free of bureaucratic layers, permitting a level of individualism,
creativity, and innovation beyond the reach of any hierarchy. The network's core
is a guiding coalition that represents each level and department in the
hierarchy, with a broad range of skills. Its drivers are members of a "volunteer
army" who are energized by and committed to the coalition's vividly formulated,
high-stakes vision and strategy. Kotter has helped eight organizations, public
and private, build dual operating systems over the past three years. He predicts
that such systems will lead to long-term success in the 21st century--for
shareholders, customers, employees, and companies themselves.
PMID- 23155998
TI - The management century.
AB - In 1886, addressing the nascent American Society of Mechanical Engineers, Henry
R. Towne proposed that "the management of works" be considered a modern art-
thereby heralding the Management Century, when management as we know it came into
being and shaped the world in which we work. Kiechel, a past editorial director
of Harvard Business Publishing, elucidates the three eras that punctuate this
period: the years leading up to World War II, during which scientific exactitude
gave wings to a new managerial elite; the early postwar decades, managerialism's
apogee of self-confidence and a time when wartime principles of strategy were
adapted, sometimes ruthlessly, to the running of companies; and the 1980s to the
present, years that saw fast-moving changes, disequilibrium, and a servitude to
market forces but also ushered in globalism, unprecedented innovation, and
heightened expectations about how workers are to be treated. Along the way he
examines the contributions of thinkers such as Frederick Taylor, Elton Mayo,
Peter Drucker, and Michael Porter. What lies ahead? Perhaps the biggest challenge
facing the 21st-century company, Kiechel posits, is to truly free the spark of
human imagination from the organization's tidal pull toward the status quo.
There's almost always a better way, he concludes--and management will continue to
seek it.
PMID- 23155999
TI - Does management really work?
AB - HBR's 90th anniversary is a sensible time to revisit a basic question: Are
organizations more likely to succeed if they adopt good management practices? The
answer may seem obvious to most HBR readers, but these three economists cast
their net much wider than that. In a decadelong study of thousands of
organizations in 20 countries, they and their interview teams assessed how well
manufacturers, schools, and hospitals adhere to three management basics: targets,
incentives, and monitoring. They found that huge numbers of companies follow none
of those fundamentals, that adopting the basics yields big improvements in
outcomes such as productivity and longevity, and that good nuts-and-bolts
management at individual firms shapes national performance. At 14 textile
manufacturers in India, for example, an intervention--involving free, high
quality advice from a consultant who was on-site half-time for five months--cut
defects by half, reduced inventory by 20%, and raised output by 10%. A control
group saw no such gains. The authors' global data set suggests that implementing
good management at schools and hospitals yields change more slowly than at
manufacturers--but it does come eventually. And the macroeconomic potential--for
incomes, productivity, and delivery of critically needed services--is huge. A
call for "better management" may sound prosaic, but given the global payoffs,
it's actually quite radical.
PMID- 23156000
TI - Deal making 2.0: a guide to complex negotiations.
AB - Most big deals--megamergers, major sales, infrastructure projects--are built on a
series of smaller ones. Each component deal presents a tactical challenge, but
sequencing the parts in a way that achieves the target outcome is a strategic
challenge that can unfold over months or years. This process, which the authors
call a negotiation campaign, must generally be conducted on several fronts, each
involving multiple parties. A multifront campaign can be much more effective than
direct negotiation. After failed talks between Longshoremen and the Pacific
Maritime Association--a group of shippers and port operators--the PMA's president
turned away from the bargaining table and embarked on a campaign to align member
firms, the business community, the U.S. government, and the public around his
target outcome: the deployment of new information technologies to help unclog
busy ports. The result was an agreement that was ultimately mutually beneficial.
Designing and executing a negotiation campaign involves identifying the relevant
parties, grouping them into fronts according to shared interests, determining
whether to combine fronts (if, for instance, doing so would unite your allies),
and deciding which fronts to approach early on and which to engage only after
you've made progress elsewhere. The deal between the PMA and the Longshoremen
involved high stakes, but many small-scale deals--such as gaining approval for a
new product--also play out on multiple fronts. Going straight to a key decision
maker often makes sense, but in many cases a multifront campaign is the only way.
PMID- 23156001
TI - A campaign strategy for your career.
AB - Organizations are inherently political, and pretending they're not is just plain
impractical. But strategizing like a politician to advance your career doesn't
have to mean compromising your integrity. You can craft a campaign plan that
actually gets results without making you feel soiled. So argues Clark, who has
worked with top-tier politicians and business executives as they strive to
achieve their goals. She recommends that in business, as in politics, aspiring
leaders choose their career milestones from the get-go and plan precisely what
reaching each one will demand. That means taking inventory of the skills you'll
need to acquire and figuring out exactly where and how you'll develop them. The
best career planners work backward on the calendar: They start with the end
points and carefully mark, in reverse, all the steps along the way. Then they set
out on the course, identifying influential people whose favor they need to win
and getting specific about how to garner it. They use power maps to home in on
the most influential individuals and groups, and they aren't shy about courting
votes. "Being political" still sounds negative to many people in business, but
learning how to play the game doesn't have to be a Machiavellian endeavor.
Indeed, harming people in the process won't help you at all, but if you eschew
the political process altogether, you'll only harm yourself.
PMID- 23156002
TI - How hard should you push diversity?
PMID- 23156003
TI - Spanking in the schools. Should teachers be allowed to paddle students?
PMID- 23156004
TI - Don't trash these gene. "Junk" DNA may lead to valuable cures.
PMID- 23156005
TI - This issue has attitude.
PMID- 23156006
TI - A national voice rings loud.
PMID- 23156007
TI - Protein requirements: time to re-evaluate Canadian recommendations.
PMID- 23156008
TI - New flu shot policy raises concerns.
PMID- 23156009
TI - Mental illness in the workplace costs billions.
PMID- 23156010
TI - What's new in patient safety.
PMID- 23156011
TI - Cumulative incidence and incidence rate.
PMID- 23156012
TI - Extra. Extra. Opportunity is knocking. Will you answer?
PMID- 23156013
TI - The care utilizing evidence initiative.
PMID- 23156014
TI - More time for care. An innovative program more time transforms wards by reducing
clutter and cutting time-wasting activities for nurses.
PMID- 23156015
TI - Get on board with the research ethics review process.
PMID- 23156016
TI - Unreported incidents, wellness program strategies.
PMID- 23156017
TI - Fighting the good fight.
PMID- 23156018
TI - Recognizing refugees as human beings.
PMID- 23156019
TI - Anesthesia error results in death: verdict for $20 million cut to $4 million.
Boudreaux v. Pettaway, 1100281 ALSC -- SO.3d -- (9/28/2012)-AL.
PMID- 23156020
TI - Arbitration agreement signed by daughter with POA ruled unenforceable. Case on
point: Ping v. Beverly Enterprises, Inc., 2010 SC 000558 DG--S.W.3d--(8/23/2012)
KY.
PMID- 23156021
TI - FL: Claims for injury released in suit in state 1: defendants-not named in
release-sued in state 2. Berrios v. Orlando Regional Healthcare System, 5D11-3727
FLCA5 (9/21/2012)-FL.
PMID- 23156022
TI - MA: Failure to follow 'care plan': bones broken: appeals court reversed order to
dismiss case. Pitts v. Wingate at Brighton, Inc., 82 Mass. App. Ct. 285,
(7/26/2012)-MA.
PMID- 23156023
TI - Over $2 million dollar award for death from delivery error affirmed. Case on
point: Hatwood v. Hospital of Univ of Penn., 2012 PA Super 217 (10/5/2012)-PA.
PMID- 23156024
TI - [Current state and trends in development of Russian radiologic equipment].
PMID- 23156025
TI - [A modified radiation kilovoltmeter for X-ray diagnostic apparatuses].
PMID- 23156026
TI - [Portable X-ray apparatuses for dentistry and maxillofacial surgery].
PMID- 23156027
TI - [Calibration of thermoluminescent dosimeters used for measuring the effective
dose in computer tomography].
PMID- 23156028
TI - [Estimation of the operating life of an X-ray tube anod].
PMID- 23156030
TI - [Solution of the X-ray topographic problem for a stereo pair of scanned images].
PMID- 23156029
TI - [A matrix gallium-arsenide detector for roentgenoraphy].
PMID- 23156031
TI - [Calculation of the radiation parameters of an X-ray apparatus from its
spectrum].
PMID- 23156032
TI - [Reduction of the radiation load in digital X-ray diagnosis].
PMID- 23156033
TI - [Reduction of the working temperature of X-ray tube bearings].
PMID- 23156034
TI - [Radiation load exerted by PARDUS portable dental X-ray apparatuses].
PMID- 23156035
TI - [New requirements to the radiation protection in X-ray surgery].
PMID- 23156036
TI - [Microfocus roentgenography: an innovative medical diagnostic technology].
PMID- 23156037
TI - [Rapid analysis of suppositories by quantitative 1H NMR spectroscopy].
AB - Rapid analysis of suppositories with ibuprofen and arbidol by quantitative 1H NMR
spectroscopy was performed. Optimal conditions for the analysis were developed.
The results are useful for design of rapid methods for quality control of
suppositories with different components
PMID- 23156038
TI - [Search for new types of raw materials for antibacterial drugs].
AB - Antibacterial properties of the mycelium culture of Fomitopsis officinalis
(Vill.: Fr.) Bondartsev et Singer were investigated. It was shown to be an
additional source for production of antibacterial substances active against
gramnegative bacteria. In the future, the use of Fomitopsis officinalis for
production of antibacterial substances active against the pseudotuberculosis
pathogen or pseudomonads is quite possible.
PMID- 23156039
TI - [Expression of estrogen receptors beta and beta1 in tissue of human non-small
cell lung cancer].
AB - Comparability of the level and intensity of estrogen receptors beta (ERbeta)
expression in non-small cell lung cancer tissue of 32 patients was analyzed by
flow cytometry using various antibodies--to the total fraction of ERbeta (clone
14C8) as well to the full-length ERbeta1 isoform (clone EMRO2). The differences
in the ER expression indexes detected by anti-ERbeta or anti-ERbeta1 antibodies
were revealed in some patients, but it had no influence on average indexes of the
ERbeta expression in the patient groups investigated. It was confirmed by the
findings on more frequent and more intensive expression of ERbeta in the non
small cell lung cancer tissue of female patients vs. the males irrespective of
antibody type - anti-ER/ or anti-ERbeta1. Therefore, in comparative analysis of
ERbeta expression in the groups of the patients with different clinicomorphologic
characteristics of the disease it is possible to use both the antibodies. For
individual disease prognosis in the routine clinical practice it is recommended
to use the antibodies to the total fraction of ERbeta, since there are individual
differences between the ERbeta expression indexes revealing by various types of
antibodies.
PMID- 23156040
TI - [Increase of antibacterial therapy efficacy in chronic sepsis with cycloferon and
reamberin combination].
AB - The use of reamberin and cycloferon combination for increasing the antibacterial
therapy efficacy in patients with chronic sepsis (CS) was studied. It was shown
that the combination provided more rapid elimination of the CS exacerbation
symptoms, normalization of the hematologic indices, bacteriemia eradication and
reduction of the cytokine blood profile--normal serum levels of proinflammatory
(IL-1beta, IL-2, IL-6 and TNF-alpha) and antiinflammatory (IL-4) cytokines. The
findings allowed to considered the use of the reamberin and cycloferon
combination in the treatment of patients with CS pathogenetically reasonable and
clinically perspective for increasing the antibacterial therapy efficacy.
PMID- 23156041
TI - [Impact of hypoxen therapy on postoperative course in gynecologic patients].
AB - The aim of the study was to estimate the use of hypoxen (antihypoxant) during the
early postoperative course in gynecologic patients. The patients were divided
into two groups according to the treatment scheme. 339 patients of the control
group were under the routine therapy after the laparatomic gynecologic
operations. 52 patients were additionally treated with hypoxen (antioxidant) (the
main group). The impact of hypoxen on the antioxidant system and lipid
peroxidation and its preventive effect on prolongation of the postoperative pain
syndrom were estimated. The results of the study showed that hypoxen inhibited
lipid peroxidation and activated the antioxidant system in the postoperative
patients vs. the control group. It was also observed that among the patients
additionally treated with hypoxen the percentage of those with prolonged
postoperative pains was statistically lower (p<0.05, chi2 test). It was concluded
that hypoxen normalized lipid peroxidation and antioxidant system after abdominal
gynecologic operations. The additional use of hypoxen in the routine therapy of
the gynecologic patients prevented prolongation of the postoperative pain
syndrom.
PMID- 23156043
TI - [Hepatotropic therapy in treatment of liver injury].
AB - At present, the conception of the use, efficacy and safety of hepatotropic agents
in treatment of drug-induced liver injury, in particular due to antituberculosis
drugs is not yet final, which is conditioned by extremely rare clinical trials on
the subject adequate to the up-to-date principles of the conclusive medicine. The
review presents data on the hepatotoxic effect of antituberculosis drugs,
analysis and systematization of the data on the use of hepatotropic agents in
liver injury induced by antituberculosis drugs, the principles and
characteristics of their clinical use. The mechanism of action of remaxol, a new
original hepatotropic agent and the indications of its use are discussed. The
experimental findings on the remaxol ability to decrease the antituberculosis
drug-induced liver injury through lowering the carbohydrate, albuminous and fatty
degeneration and activating the organ reduction are presented. The clinical
trials are evident of the most efficient action of remaxol on the signs of
toxemia, as well as cytolysis and cholestasis, which along with its antiasthenic
and antidepressant action allows to use remaxol as an universal hepatotropic
agent in the treatment of diverse drug-induced liver injuries in both the
therapeutic and prophylactic schemes.
PMID- 23156042
TI - [Diagnostic and treatment patterns in management of male patients with
nongonococcal urethritis: results of Russian multicentral cross-sectional study].
AB - The aim of the study was to estimate the diagnostic and treatment patterns in the
management of acute nongonococcal urethritis (NGU) in males in some cities of
Russia. Retrospective cross-sectional study was conducted in 2009 in 5 centers of
4 cities in the Central Part of Russia (Kaluga, Pskov, Smolensk - 2 centres and
Tula). The data on the diagnostic and treatment approaches to the management of
NGU in male subjects >16 years old were collected and analyzed with the use of
specially designed case report forms. 556 cases of acute urethritis were analyzed
during the study. The diagnosis of NGU was confirmed in 401 cases. The average
age of the patients was 29.8 years (16-68 years). The following diagnostic
methods were used in 95% of the cases: urethral smear microscopy (314/82.4%), C.
trachomatis - PCR (113/29.7%), ELISA (155/40.7%); T. vaginalis - PCR (106/27.8%);
U. urealyricum and M. hominis, respectively - bacteriology (140/36.7% and
126/33.1%), PCR (110/28.9% and 108/28.3%); M. genitalium - PCR (110/28.9%). The
treatment patterns included antimicrobials AMs alone in 60.3, and AMs + non-AMs
in 37.8% of the cases. The most frequently prescribed AMs were azithromycin
(27.5%), fluconazole (16.4%), doxycycline (13.6%), metronidazole (11.2%),
ofloxacine (7.3%), ceftriaxone (4.4%), josamycin (4.2). According to the results
use of the standard methods for NGU diagnosis was rather rare. The use of PCR for
atypical pathogens was the following: C. trachomatis 29.7%, U. urealyticum 36.7%,
M. hominis 28.9%, M. genitalium 28.3%. Doubtful culture methods were used for
detection of U. urealyticum and M. hominis (36.7% and 33.1%). The AMs treatment
in some cases was not in compliance with the up-to-date practical guidelines for
STD and NGU.
PMID- 23156045
TI - [Comparative analysis of modern approaches to risk estimation from artificially
created nanoparticles and nanomaterials].
AB - The article represents a review of modern approaches to problem of
nanotechnologies and nanomaterials risk estimation for human health and
environment that were elaborated in EU, USA and some international authorities.
Submitted data suggests that there is a significant coincidence with approaches
being developed and introduced in Russian Federation under the guidance of
Rospotrebnadzor. Particularly criteria being used in Russian Federation and EU
for classification of nanotechnologies and nanoindustry production are mainly
similar. They include a) identification of nanomaterials in production, b)
establishment of production disintegration possibility with concomitant migration
of free nanoparticles, c) possibility of nanoparticles emission/migration both in
normal conditions of utilization and in possible emergency conditions, d) degree
of proximity of particular kind of production to it's consumer that means the
possibility of exposition being from closely to zero (in conditions of
unhabitated exploitation) up to approximately 100% (in case of medicine, food and
cosmetics), e) biological examination of potential danger of nanomaterials
according to current volume of scientific information. As applied to
nanotechnology plants there are such criteria in use as a) nanomaterial
identification, b) personnel exhibiting possibility, c) potential toxicity of
stuff in aerosol nano-form, d) characteristics of biological action. Thus applied
in Russia principles for nanomaterials safety estimation do not contradict to
concepts of foreign authorities that builds up a possibility of said approaches
harmonization to internationally recognized norms.
PMID- 23156044
TI - [The analysis of international legislation in the field of regulation of
functional foods claims].
AB - It is known that manufacturers quite often put into foodstuff marking or
advertisement the information about its beneficial action into the consumers
health, i.e. about its functional qualities. However in Russian Federation the
rules are regulated using of term "functional foods" doesn't established. In the
review of legislation acts which are regulated of using claims in the foodstuff
marking or advertisement in the different countries have been shown that claims
concerning of energy and nutritional values of foods (beneficial nutrition
claims) should be used in compliance with established rules without additional
investigations. Food health claims referring to the reduction of disease risk and
(or) functional foods claims for children must maintain in compliance with
established procedure. Only claims that have scientific evidence about its
beneficial for health could be recommended for approval. Thereupon insistent
necessity in development, discussion and approval regulation in the field of
using Claims concerning the functional qualities of foods (described rules of
using beneficial nutrition claims and claims referring to the reduction of
disease risk and to children's development and growth) in Russian Federation and
United Customs Union (EurAsEU) are obvious.
PMID- 23156046
TI - [Oxidative and hydrolytic deterioration of palm oil and fat products based on it
under various conditions of storage and transportation].
AB - Studies have been conducted on the effect of storage conditions for refined
deodorized palm oil on the quality and safety: in containers made of ferrous
metals (mild steel) at unregulated temperature, in sealed plastic bags at the
temperature -20 degrees C in stainless steel under stratification of nitrogen at
the temperature of 40+/-1 degrees C. The choice of the objects of study
determined by the normative documents of the Russian Federation governing the
transportation and storage of vegetable oils and fat products based on them. All
samples of palm oil with peroxide value of 1,0 to 1,5 meq O2/kg indicated the
presence of a weak foreign taste, is not peculiar impersonalfat, the samples with
peroxide value above 1,5 meq O2/kg were observed pronounced off-flavors and odors
characteristic of stale oil. Rancidity was observed in samples having peroxide
value of 2,0 meq O2/kg or more. Free acid value and anizidin value for the
studied period changed to a lesser extent, from 0,06 to 0,1 mg KOH/g and from 1,2
to 1,4 respectively. It is proved that, transportation/storage of palm oil at the
temperature above 50 degrees C without stratification of nitrogen greatly
accelerates the process of oxidative damage. Based on these data we can recommend
transportation/storage and management process with the least possible time of
contact of melted palm oil with oxygen to produce high-quality final product
(within 2-3 hours from the time of melting).
PMID- 23156047
TI - [The morbidity dynamics of alimentary-associated diseases in children and
adolescents in Northern administrative district of Moscow over a period of 2006
2010].
AB - Through socio-hygienic monitoring of the Northern administrative district of
Moscow in 2006-2010 the study of nutritional status and morbidity rates for
alimentary-associated diseases of the digestive tract, the endocrine system,
cardiovascular diseases and obesity - was conducted in children (5-11 years old),
adolescents (12-16 years old) and adult population. Over the last 5 years
negative dynamics in morbidity rates for the illnesses related to malnutrition
and nutritional status disturbances was shown in children and adolescents. Thus
it was noted a considerable increase of alimentary-associated diseases among
children (2,3 times more) and adolescents (2,1 times more). This applies
especially to gastrointestinal diseases (gastritis, duodenitis, etc.) and obesity
which prevalence increased over the last 5 years among children (under 5 years
old) 2,4 times more; and 2,1 times more among teenagers. In children and
adolescents from the district gastrointestinal diseases amount to 15,6%
ofallnutrition-related diseases. The authors of the article emphasize that
currently hygiene education of the population (including children and
adolescents) must become a key tool in implementing the state policy in the area
of healthy nutrition and in activities of the primary care health service to
prevent nutritional disturbances and decrease the prevalence rate of alimentary
associated diseases with special attention from nutritionists, dietarians, and
hygienists.
PMID- 23156048
TI - [Nutritional status in patients after gastrectomy due to gastric cancer].
AB - Aim of the study was to evaluate nutritional status in patients after gastrectomy
due to gastric cancer. METHODS: In 55 (26 males and 29 females) gastric cancer
patients after gastrectomy body composition (bioimpedansometry method); resting
energy expenditures and home actual nutrition (frequency analysis method) were
evaluated. Blood levels of major nutrients and metabolites were assessed.
RESULTS: Both men and women suffered from weight loss after gastrectomy (mean BMI
was 19,8+/-4,7 kg/m2 in men and 20,5+/-1,9 in women). Higher BMI was positively
correlated with age in women (R=0,45; p<0,03), but not in men, however there was
no difference in mean age and mean time after gastrectomy between men and women.
Mean body fat mass significantly decreased in men (7,4+/-5,0 kg) and in women
(12,0+/-7,1 kg) in compare to normal values (18,2 and 22,5 correspondingly)
(p<0,001). Resting energy expenditure variably decreased (for 13-53%) in half of
the patients, mainly due to decrease in lipid oxidation rate. Mean daily energy
intake was lower than normal in short-term (1359 kcal in period of 12 months) and
long-term (1814 kcal in 1-5 years period) after gastrectomy, due to decrease
consumption of proteins, carbohydrates and fat. Mean blood total protein,
hemoglobin and hematocrit levels were lower than normal values in 40% of
patients. CONCLUSION: In gastric cancer patients low BMI, low fat mass and energy
consumption are observed even long period of time after gastrectomy. Dietary
counseling and support are badly needed in patients short-term as well as long
term period after gastrectomy in men and younger women.
PMID- 23156049
TI - [Effect of diet enriched with selenium on the psycho-emotional and adaptive
capacity of patients with cardiovascular diseases and obesity].
AB - It was studied the effect of diet enriched with selenium on the clinical and
biochemical status, psycho-emotional and adaptive capacity of the organism in
patients with diseases of the cardiovascular system. We examined 59 patients with
cardiovascular disease and obesity, treated for 3 weeks antiatherogenic reduced
calorie diet. Of these 36 patients from the index group took on the back of
ground diet selenium containing diet product (part of alimentotherapy). Patients
underwent clinical examination, biochemical parameters and the availability of
selenium were measured. To assess the adaptive capacity of the organism we used
Program Apparatus Complex. Quality of life of patients, overall health, level of
anxiety and the dynamics of mental processes were assessed using SAS procedures,
Spielberger-Hanin anxiety test, Serdyuk Quality of Life Questionnaire,
Kraepelin's counting test. The results indicate positive changes in clinical and
biochemical status, availability of selenium, adaptive capacity, psycho-emotional
state of patients with cardiovascular disease and obesity because of the diet
enriched with organic form of selenium. We revealed increase in activity,
improvement of overall health and cognitive functions, mood stabilization,
reduction of anxiety and emotional lability. The main differences observed
between the groups identified in the leveling of the anxiety radical in psycho
emotional status of patients.
PMID- 23156050
TI - [Role of alimentary factor in gastroesophageal reflux disease pathogenesis and
treatment].
AB - The aim of the study was to evaluate the impact of meal volume, weight change,
excessive weight, and caloric content of the ration on disease's manifestation
and progression from data presented in the published scientific literature.
Systematic review in PubMed/Medline databased was performed with key words: food,
dietary patterns, nutrients, nutrition, meal volume, calorie in combination with
gastroesophageal reflux and GERD. 113 articles were found and 29 of them were
selected according to the following criteria: the article should contain data of
clinical observations, or to be a result of meta-analysis; study group
characteristic, study design, and results should have been available for the
analysis. The review contains data concerning influence of body mass index, its
change; meal volume and caloric content of the ration on clinical manifestations
of GERD. The dietotherapy recommendations for this illness include exclusion of
overeating, limitation in use of high-caloric foods, increased protein content in
diet, the adherence of 3-4 meals daily, with the last meal at 2-3 hours before
sleep. However, the majority of the recommendations on the use of dietary
nutrition is mainly based on the empiric experience, not on scientific data, and
that doesn't allow to prepare reasonable recommendations for changing the diet of
the patients with GERD. There is a need for prospective studies of influence of
diet correction on course of the disease.
PMID- 23156052
TI - [Digestive enzyme functionality in pathology of the gastrointestinal tract with
intestinal microbiocenosis disorders].
AB - A change pattern in enzyme release function of digestive glands exerts the
organism as a whole. Dysfunctions of hydrolysis and intestinal malabsorption
(secondary malabsorption syndrome) are the first step towards nutrition and
metabolism processes abnormality and that can play a role in genesis of
pathological conditions. Recent researches arouse clinicians interest in
determination of biofluid enzyme activity in different physiological and abnormal
cases. Intestinal infections are followed by dysbacteriosis and obvious
alterations in the hydrolase levels in the blood, urine and motions because of
the changes of functional status of the liver, renal and intestinal barriers in
relation to increted digestive enzymes. This causes an unfavorable course of
recovery with the development of postinfectious digestion disorders as a result
of previous acute diarrhea. Future researches are necessary to elaborate
appropriate remodeling of developed pathosis with the help of enzymotherapy and
probiotic diet.
PMID- 23156051
TI - [Modern concepts of gene polymorphisms, which regulate lipid metabolism].
AB - This review discusses the present view on lipid metabolism regulation with
emphasis on polymorphisms of key genes. Relying on the analysis of the
literature, the blood lipid specter of carriers of the key genes allelic variants
has been described. Therefore, reasonability of a more profound study of the
influence of genetic polymorphisms on lipid metabolism regulation is
substantiated. It is revealed, that the carriers of one of the abnormal alleles
causes a higher risk for obesity and its associated complications. Polymorphic
variants of the genes, that regulated lipid metabolism are widely presented in
human population. It explains the big interest to studying of communication
between dyslipidemia, adiposity and other pathologies with features of a
genotype. However, abnormality of metabolic process and associated diseases in
most cases represent multifactorial diseases. For today, the important problem
for researchers still is a definition of a role of individual genetic features in
development of pathological processes. The special attention in researches of
last years is given to the genes, which products concern to leptin-melanokortin
system of regulation of a energy metabolism; proteins-carriers lipid's blood
fractions and cholesterol; and also the enzymes splitting lipids. Lipid
metabolism is closely connected with an exchange of carbohydrates, especially a
glucose metabolism. That is why genes mediating actions of insulin represent the
greatest interest. Today, more than 400 genes are the potential candidates,
capable to regulate lipid exchange. However, the further careful and extensive
researches in this area are necessary.
PMID- 23156053
TI - [Peculiarities of vitamin status in men and women with cardiovascular disease and
obesity].
AB - We explored the characteristics of the vitamin status in 471 patients with
cardiovascular diseases, according to sex, and BMI values. All patients underwent
examination of the system Nutritest-IP: studying their actual meals at home,
determined anthropometric measurement, body composition, using biochemical
methods evaluated the state of the protein, lipid and carbohydrate metabolism,
the functional state of liver and biliary tract, hemostasis, vitamin provision.
The results suggest a lack of availability of patients with vitamins C and B
group. The number of patients with deficient serum beta-carotene increased
proportional to body mass index. The concentration of beta-carotene decreased and
vitamin E - increased in blood serum proportionally to increase the degree of
obesity. Thus the availability of vitamins in the blood serum depends from sex
and body mass index values of the patients. These data suggest that the rate of
supply of vitamins are reliable markers to assess the adequacy of the diet
consumed by the content of vitamins in people with normal body weight.
Appraisingly the content of beta-carotene and vitamin E in the serum of patients
it should be taken into account that they have overweight or obese, and
abnormality of lipid spectrum of blood serum.
PMID- 23156054
TI - [Vitamins in rat experimental diets].
AB - A comparison of full semisynthetic diets used in different laboratories has shown
that its vitamin content covers physiological requirements of rats in these
micronutrients. The significant fluctuations in group B vitamin concentrations
may take place when one uses brewer's yeast as a source of these vitamins. A
preliminary assessment of vitamin content in brewer's yeasts is required in this
case. An essential contribution of basic components in diet vitamin content must
be taken in consideration when one creates a vitamin-deficient diet. Casein
contains substantial amounts of group B vitamins and vitamin D. Therefore
decontamination of casein from water and / or fat-soluble vitamins or the use of
commercial purified casein is required. Vegetable oils are usually used as a
fatty component of a diet and they simultaneously serve as an additional source
of vitamin E. A choice of naturally containing vitamin E oil as a fat component
of a diet is crucial for the creating an alimentary deficiency of vitamin E. The
content of fat-soluble vitamins in the diet of control group (group of
comparison) and vitamin level in the diet of experimental group of animals must
be equivalent in investigations with modified (quality and quantitative) fat diet
component. Caloric restriction by simple reducing of food without increasing the
amount of vitamins to an adequate level is incorrect. With these considerations
in mind proper attention to the equivalence of vitamin content in the diet of
animals in experimental and control groups should be paid during experiments
scheduling. Otherwise, the studies carried out under deficient or excessive
intake of vitamins can lead to incorrect interpretation of the results and
difficulties in their comparison with the data obtained under different
conditions.
PMID- 23156055
TI - [The mineral composition of the carbohydrate-electrolyte drinks, vitamin-mineral
complexes and dietary supplements for athletes].
AB - In the article analyzes the macro- and trace element composition of sports
drinks, vitamin-mineral complexes and biologically active additives (BAA). The
estimation of the mineral collection of these products compared with the
recommended standards. Established mineral composition many of the carbohydrate
electrolyte solutions, vitamin-mineral complexes and biologically active
additives corresponds the physiology standards. However in some vitamin-mineral
complexes and especially biologically active additives a number of minerals can
be either unreasonably low or unreasonably high. Furthermore during labeling,
mainly in the category D, a number of errors were revealed. Particularly there
were lack of instructions about the number of declared ingredients, inaccuracies
in the calculations of the daily requirement of mineral elements etc. Providing
of an athlete organism with minerals should be carried out not only by
carbohydrate-electrolyte solutions, vitamin-mineral complexes and specialized
BAA, but mainly through basal ration. Utilising of carbohydrate-electrolyte
solutions, vitamin-mineral complexes and biologically active additives can be
justified only by the recommendations of experts. This is true not only in pro
sports, but for the mass sports, as well as for individual physical training, in
order to maintain physically fit.
PMID- 23156056
TI - [To the 90th anniversary of State Sanitary Epidemiologic Service Formation in
Russian Federation].
AB - State Educational Institution of Higher Professional Training of the Ministry of
Health Care and Social Development Foundation of Russian Sanitary Epidemiologic
Service dates back to September, 15, 1922, when a Decree on Sanitary Institutions
of the Republic was signed. Afterwards the institutions of Sanitary Epidemiologic
Service were improved: foundation of State Sanitary Inspectorate (1933-1951),
approval of new concept of the Service and intensification of State Sanitary
Inspectorate (1951-1991), foundation of State Sanitary Epidemiologic Service,
centralization of management and financing of the Service, formation of Sanitary
Epidemiologic Legislation (1991-2004), further restructurization of Sanitary
Epidemiologic Service in accordance with administrative changes in Russia (2004
until now).
PMID- 23156057
TI - [Problems of more healthy work conditions, occupational diseases prevention on
enterprises of major economic branches].
AB - The article deals with evaluation of contemporary work conditions in mining
enterprises, iron industry, aluminium production plants. Work conditions are
classified according to hazard level and jeopardy in various occupations within
the enterprises. Reports presented by Russian Mining Metallurgy Trade-union on
occupational morbidity over 2002-2010 were summarized. Occupational morbidity
parameters were defined, their increase was identified, structure of occupational
pathology was determined. The authors formulated suggestions in improving the
work conditions, in occupational diseases prevention in mining enterprises, iron
industry and aluminium production plants.
PMID- 23156058
TI - [Influence of occupational factors in ore-dressing and processing enterprise on
reproductive health of the female workers].
AB - The authors present data on studies of work conditions of female workers engaged
into ore-dressing and processing enterprise, occurrence of gynecologic diseases,
and results of retrospective analysis of pregnancy and delivery course over 2001
2010. Findings are that work conditions in the industry increase gynecologic
diseases risk and complications rate during pregnancy and delivery.
PMID- 23156059
TI - [Evidence-based medicine in evaluating occupational health risk in workers
engaged into graphite ware production].
AB - The article deals with results of epidemiologic study on evaluating the health
state of workers engaged into graphite ware production, through three various
parameters based on data about chronic non-occupational diseases. The authors
evaluate carcinogenic risk for the population residing on various distances from
the enterprise.
PMID- 23156060
TI - [Immunopathogenetic features of occupational bronchitis].
AB - The article based on research work covers functional, bronchoscopy, microbiologic
and immunologic features of chronic dust bronchitis and chronic bronchitis caused
by toxic chemicals.
PMID- 23156061
TI - [Lipid metabolism in occupational chronic bronchitis associated with diabetes
mellitus].
AB - The study of 311 patients with chronic occupational bronchitis associated with
diabetes mellitus (or diabetes-free) revealed lipid metabolism disorders
presenting with overweight, obesity, dyslipoproteinemia. Diabetes mellitus
addition to chronic bronchitis increased frequency of lipid metabolism disorders
and higher values of lipid state. The revealed lipid metabolism disorders were
more marked in the females.
PMID- 23156062
TI - [Gender differences in death causes and survival rate of silicosis patients].
AB - The authors analyzed structure of mortality and survival rate in 284 silicosis
patients over 14 years. Findings are that the mortality structures among the
females and the males with silicosis are different. In both groups compared, the
first place among death causes was occupied by cardiovascular diseases. The
females with silicosis were more frequent to die with broncho-pulmonary
conditions, vs. the males of the same group. However the survival rate among the
females over the studied period was higher than that among the males.
PMID- 23156063
TI - [Biologic markers for early diagnosis of effects caused by exposure to coal dust
in miners].
AB - The authors studied changes in several laboratory values of coal miners in
Russian Federation, defined information value of these changes and suggested
complex of methods for early preclinical diagnosis of negative effects caused by
coal dust in the miners. Dust-related respiratory diseases were proved to develop
by stages on molecular level.
PMID- 23156064
TI - [Practical experience of applying Order 302n released by Russian Federation
Health and Social Development Ministry on April 12, 2011 "On approving the lists
of hazardous and (or) dangerous occupational factors and works that require
obligatory preliminary and periodic medical examinations (workup) and on regimen
of obligatory preliminary and periodic medical examinations (workup) for workers
exposed to intense labor and to hazardous and (or) dangerous work conditions"].
AB - The analysis covered practical activities of medical department of Open-end Joint
Stock Company, connected with the Order 302n released by Russian Federation
Health and Social Development Ministry on April 12, 2011 "On approving the lists
of hazardous and (or) dangerous occupational factors and works...". Findings are
drawbacks in organization and carrying out the medical examinations mentioned in
the Order. Financial and economic content of the medical examinations is
evaluated. Some social consequences of the document are presented, and measures
to optimize and adjust the Order to its practical application are suggested.
PMID- 23156065
TI - Component-resolved diagnosis-assisted prescription of allergen-specific
immunotherapy: a practical guide.
AB - Allergen specific immunotherapy remains the only means to change the natural
history of allergic disease. Thanks to the recent advances in molecular biology a
large spectrum of purified allergen molecules are presently routinely available
for diagnostic purposes. This review represents a practical guide on how to use
these new diagnostic tools in order to detect precisely the primary sensitizing
allergen sources in subjects showing a multiple sensitization to seasonal and/or
perennial airborne allergens, thus avoiding the diagnostic mistakes that have
been probably associated with the prescription and administration of several
ineffective immunotherapies up to a recent past.
PMID- 23156066
TI - Serum eotaxin levels in patients with chronic spontaneous urticaria.
AB - Eotaxin is a potent agonist for CC chemokine receptor 3 that can attract
eosinophils at sites of inflammation. Given the potential role of eosinophils in
chronic spontaneous urticaria (CU), we measured serum eotaxin levels together
with C-reactive protein in 100 CU patients who were characterized according to
autologous serum skin test (ASST) and disease severity. Serum eotaxin
concentration was significantly higher in CU patients (median 140.1 pg/ml, range
33.7-718.7 pg/ml) than in 45 healthy controls (median 108.9 pg/ml, range 45.5
409.4 pg/ml) (p = 0.032) Serum eotaxin concentration was not significantly
different in ASST-positive and ASST-negative patients as well as in patients with
different urticaria activity scores. However, eotaxin levels tended to be higher
in patients with intense symptoms. In the 7 patients observed during CU
exacerbation and during remission, eotaxin serum levels tended to decrease during
remission, although statistical significance was not reached (median
concentration decreased from 170.0 pg/ml to 123.8 pg/ml). CRP levels were not
significantly different in CU patients and healthy subjects, although there was a
trend towards higher levels in the former population. Furthermore, in the 7
patients observed during CU exacerbation and during remission, CRP levels
decreased significantly during remission (median concentration dropped from 4.1
microg/ml to 0.7 microg/ml, p = 0.015). No significant correlation was found
between eotaxin and CRP serum levels. These findings indicate that serum eotaxin
levels are increased in CU patients, although they do not reflect strictly
disease activity. A role for eotaxin in eosinophil attraction and activation in
CU can be envisaged.
PMID- 23156068
TI - Sensitization to rodents (mouse/rat) in an urban atopic population without
occupational exposure living in Naples, Italy.
AB - BACKGROUND: Until now no data on allergic sensitization to rodents allergens in
Western Europe and Italy are available. The aim of this report was to investigate
clinical significance and characteristics of IgE-mediated sensitization to
mouse/rat (M/Rt) allergens in atopic subjects not occupationally exposed to these
animals and living in urban area of Naples. METHODS: In 1765 consecutive
outpatients, we selected all subjects with an immediate skin reaction to M/WRt
dander clinical history including a carefijul evaluation ofthe modality of
exposure, the results of skin-prick tests (SPTs) and specific IgE antibodies were
recorded. RESULTS: Among 1185 SPT-positive patients, 22 were sensitized to M/Rt
dander (respectively 1.60% and 0.59%). No patient was mono-sensitized Only three
of 22 patients reported indoor conditions suggesting presence of rodents
allergens at home. All patients exhibited low degree of SPT positivity and low
levels of circulating IgE antibodies to M/WRt. Highfrequency of concomitant
allergic sensitization to pet (and other animal) dander has been found.
CONCLUSIONS: Our results suggest that role of allergic sensitization to rodents
is negligible in atopic subjects without occupational exposure living in urban
area of Naples. However, highly atopic individuals especially those already
sensitized to common pet dander should be tested by SPTs/evaluation of serum
specific IgE to rodents in the case they could begin an occupational exposure to
M/Rt or keeping these animals as pets.
PMID- 23156067
TI - Knowledge and health care resource allocation: CME/CPD course guidelines-based
efficacy.
AB - BACKGROUND: Most health care systems consider continuing medical education a
potential tool to improve quality of care and reduce disease management costs.
Its efficacy in general practitioners needs to be further explored. OBJECTIVE:
This study assesses the effectiveness of a one-year continuing medical
education/continuing professional development course for general practitioners,
regarding the improvement in knowledge of ARIA and GINA guidelines and compliance
with them in asthma management. METHODS: Sixty general practitioners, covering
68,146 inhabitants, were randomly allocated to continuing medical
education/continuing professional development (five residential events +four
short distance-learning refresher courses over one year) or no training.
Participants completed a questionnaire after each continuing medical education
event; key questions were repeated at least twice. The Local Health Unit
prescription database was used to verify prescription habits (diagnostic
investigations and pharmacological therapy) and hospitalizations over one year
before and after training. RESULTS: Fourteen general practitioners (46.7%)
reached the cut-off of 50% attendance of the training courses. Knowledge improved
significantly after training (p < 0.001, correct answers to key questions +13%).
Training resulted in pharmaceutical cost containment (trained general
practitioners +0.5% vs. controls +18.8%) and greater attention to diagnosis and
monitoring (increase in spirometry +63.4%, p < 0.01). CONCLUSION: This study
revealed an encouraging impact of educational events on improvement in general
practitioner knowledge of guidelines and daily practice behavioral changes. Long
term studies of large populations are required to assess the effectiveness of
education on the behavior of physicians in asthma management, and to establish
the best format for educational events.
PMID- 23156069
TI - A case of allergy to zucchini.
AB - A case of mono-sensitization to a heat- and pepsin-stable allergen in zucchini is
described.
PMID- 23156070
TI - A case of rice allergy in a patient with baker's asthma.
AB - A case of rice allergy in a patient with bakers asthma is described. On ISAC 112
IgE reactivity to wheat alpha-amylase/trypsin inhibitor (nTri a aA_TI) and lipid
tranfer protein (rTri a 14) was found. We hypothesize that the reaction by oral
ingestion was elicited by homologous molecules in rice seeds.
PMID- 23156071
TI - Biosimilars might not measure up to health plan expectations.
PMID- 23156072
TI - Is bundled payment an idea whose time has come?
PMID- 23156073
TI - Cloud computing puts stakeholders on same page.
PMID- 23156074
TI - What the Medicaid expansion under the ACA means for all MCOs.
PMID- 23156075
TI - Three principles for improving health care delivery.
PMID- 23156076
TI - Health care resource utilization and costs associated with restless legs syndrome
among managed care enrollees treated with dopamine agonists.
AB - PURPOSE: This study assessed the direct economic burden of restless legs syndrome
(RLS) among patients treated with dopamine agonists (DAs) using a large United
States managed care database. DESIGN: Retrospective database analysis.
METHODOLOGY: Patients were required to have > or =1 prescriptions for a DA (i.e.,
pergolide, pramipexole, ropinirole) between 1/1/2005 and 12/31/2007 (date of
first DA, or "index"); continuous enrollment for > or =6 months before and > or
=12 months after index; > or =1 diagnosis of RLS, before and after index; and no
diagnosis of Parkinson's disease. Study measures included annual all-cause and
RLS-related costs by care setting (hospitalizations, emergency room, office,
pharmacy, other, total) and treatment-pattern events (discontinuations, switches,
adjunctive treatments, titrations). PRINCIPAL FINDINGS: A total of 7,796 patients
met the inclusion criteria. About 70% of patients received ropinirole, and 30%
received pramipexole at index. Approximately 91% had >1 RLS-related office
visits, and patients filled an average of 6.5 RLS-related prescriptions (DAs,
gabapentin, carbidopa/levodopa) during the 1-year follow-up period. Mean (SD) all
cause health care costs were $11,485 ($21,362) per patient, mostly due to
multiple medical conditions occurring with RLS. RLS-related costs were 6.7% of
total all-cause costs (mean [SD] $774 [$1,504]), consisting of office visits
(16%), pharmacy (63%), and other costs (20%). Approximately 58% had a treatment
pattern event suggesting a dopamine-related side effect. Opioids were the most
commonly used adjunctive therapy (13% of patients). CONCLUSION: We found
relatively low costs associated with RLS treatment. These findings should
encourage expanding the coverage of treatment to reduce the suffering and costs
associated with RLS.
PMID- 23156077
TI - Clinical bundling pays off in antisepsis campaign.
PMID- 23156078
TI - Shear bond strength comparison of two different adhesive systems.
PMID- 23156079
TI - [Similarity of cycloprolylglycine to piracetam in antihypoxic and neuroprotective
effects].
AB - The antihypoxic activity of the endogenous cyclic dipeptide cycloprolylglycine
(CPG) has been studied on a model of normobaric hypoxia with hypercapnia and its
neuroprotective activity has been studied on a model of human neuroblastoma SH
SY5Y cell damage by 6-hydroxydopamine. It is established that CPG exhibits the
antihypoxic activity at doses of 0.5 and 1.0 mg/kg (i.p.) on outbred and BALB/c
mice, but not on C57B1/6 mice. The neuroprotective activity of CPG was detected
in 10(-5) - 10(-8) M concentration range only when the treatment was carried out
24h before toxin introduction. The obtained data confirm the hypothesis that
piracetam is a mimetic of the endogenous CPG neuropeptide.
PMID- 23156080
TI - [Effect of a new triazinoindole derivative on the functional state of CNS in
animals under normoxia and hypoxia conditions].
AB - The influence of the new triazinoindole derivative encoded VM-606 on the
individual behavior of rats in the open-field and elevated-plus-maze tests has
been studied under normal conditions and after exposure to hypoxia with
hypercapnia. It is established that VM-606 at a dose of 50 mg/kg under normoxia
conditions reduces emotional anxiety, orientation-investigation activity, and
mobility factor, while under hypoxic conditions this drug reduces the severity of
behavioral changes in test animals. The experiments on mice showed that the
compound studied potentiates the hypnotic effect of hexenal. It is suggested that
VM-606 exhibits psychosedative and stress-protector properties, which play a
certain role in its antihypoxic effect.
PMID- 23156081
TI - [Effect of new derivatives of natural nitrogen-containing compounds on the level
and metabolism of biogenic amines in brain structures and the life span of rats].
AB - Effects of the analogs of transmitter amino acids on the level of biogenic amines
and their metabolism in various structures of brain and on the life span of rats
have been studied.
PMID- 23156082
TI - [Neuroprotective effects of a dipeptide mimetic on the GK-2 nerve growth factor
in model of permanent common carotid artery occlusion in rats].
AB - The behavioral and biochemical effects of a new dipeptide mimetic of the GK-2
nerve growth factor (NGF) have been studied on a model of chronic cerebral
ischemia induced by permanent common carotid artery occlusion in rats. It is
established that subchronic intraperitoneal injections of GK-2 (0.5 mg/kg) 4 h
after surgery, followed by seven more injections made every 24 h, fully prevent
the death of operated animals and reduces the development of habitation deficit
(open-field test) and decrease in exploratory activity (novel object examination)
two weeks after surgery, as well as fully restores the viability of cerebral
cortex cells and decreases the hyperexpression of HSP70 in cerebral cortex.
PMID- 23156083
TI - [Effect of losartan on acute renal failure induced by severe ethylene glycol
poisoning in rats].
AB - The effect of an angiotensin receptor II antagonist (losartan) on the model acute
renal failure (ARF) induced by severe ethylene glycol poisoning at 2/3 LD50 has
been studied in rats. It is established that losartan administration (20 mg/kg
for 72 h) produces a significant (4-fold) increase in the animal death rate,
which is associated with ARF transition to a decompensation stage. Pronounced
changes in the qualitative and quantitative composition of diurnal diuresis, more
than 8-fold increase in the creatinine level, and 18-fold increase in the blood
urea have been observed. Thus, the administration of losartan to ethylene glycol
poisoned rats causes more pronounced degeneration of proximal tubule epithelium
and destruction of glomeruli. It is concluded that the use of losartan for the
treatment of ARF is inexpedient.
PMID- 23156085
TI - [Using cytoflavin for prophylaxis and treatment of cognitive amnestic disorders
in patients with heavy toxicohypoxic damage of brain].
AB - Results of the therapy of patients with toxicohypoxic encephalopathy diagnosis
upon heavy poisoning by psychotropic substances are presented. It is established
that administration of the antihypoxant cytoflavin provides for a substantial
decrease in the extent of metabolic disorders related to the development of heavy
hypoxia. The use of cytoflavin significantly decreases the degree of
encephalopathy and favors faster and better recovery of the mnestic and other
cognitive functions in patients upon heavy toxicohypoxic brain damage caused by
acute poisoning.
PMID- 23156084
TI - [An experimental study of the anti-inflammatory action of noopept and its effect
on the level of cytokines].
AB - The anti-inflammatory effects of noopept (dipeptide analog of piracetam) upon a
single intraperitoneal (i.p.) administration at doses of 1, 5, and 10 mg/kg in
comparison to the reference drug diclofenac (10 mg/kg, i.p.) have been studied on
a model of acute exudative inflammation induced by carrageenan in outbred rats
and concanavalin A (Con A) in CBA mice. The level of cytokines was studied on the
lipopolysaccharide (LPS) model (single administration, 100 mg/kg, i.p.) with 5
day administration of noopept at a dose of 5 mg/kg (i.p., before endotoxin
injection) in C57BL/6 mice. The administration of noopept led to a significant
suppression of the inflammatory response to both carrageenan and Con A. The
administration of Con A caused a 16-fold increase in the level of IL-6
interleukin in the blood serum of mice as compared to control. Noopept (5 mg/kg)
reduced the level of IL-6 by a factor of 1.8 in the inflammatory response to Con
A. The administration of LPS led to pronounced increase in the levels ofpro
inflammatory IL-6 and TNF-alpha in the blood serum of test mice as compared to
intact animals. The course administration of noopept (5 mg/kg) significantly
decreased the level of IL-6 and reduced by half the level of TNF-alpha.
PMID- 23156086
TI - [An experimental study of the efficiency of cycloferon in the complex
chemotherapy of generalized drug-resistant tuberculosis].
AB - The results of an experimental study of the efficiency of cycloferon included in
a complex chemotherapy of generalized drug-resistant mycobacterium tuberculosis
(MBT) are presented. It is established that cycloferon (3.6 mg/kg) produces a
significant therapeutic effect, which is manifested by an increase in the lung
clearance from MBT, a decrease in the spread of specific inflammation in the
lungs, and the disappearance of MBT-induced alterations. In addition, activation
of the signs of tension in the local immunity of lung tissues is observed as
manifested by changes in the cellular composition of granulomas and more frequent
detection of large lymphocytic and macrophage infiltration. The administration of
cycloferon significantly increases the absorptive and digestive activity of
phagocytosis by peritoneal macrophages, which has been inhibited during the
development of experimental MBT infection.
PMID- 23156087
TI - [Antihypertensive and neuroprotective activity of quercetin and its derivatives].
AB - Data available in the literature on the pharmacological activity of quercetin and
its derivatives, which possess various biological properties including
antihypertensive and neurotropic activity, are reviewed. The mechanisms of these
effects and results of clinical trials are considered and prospects for the
clinical use of quercetin and its derivatives are discussed.
PMID- 23156088
TI - [Prospects for the use of plant polysaccharides in complex treatment of malignant
tumors].
AB - The pharmacological properties of plant polysaccharides are reviewed and original
experimental data on the properties of water-soluble polysaccharides isolated
from Acorus calamus L. are presented. The possibility of using plant (in
particular, Acorus calamus) polysaccharides to increase the effectiveness of
anticancer treatment of transferred tumors and to reduce the toxic effects of
cytostatic treatment on the normal cells of blood, liver, and epithelium of thin
intestine in experimental animals has been demonstrated.
PMID- 23156089
TI - Nanotechnologies and regenerative medical approaches for space and terrestrial
medicine.
AB - One purpose of the International Space Station (ISS) is to explore powerful new
areas of biomedical science in microgravity. Recent advances in nanotechnology
applied to medicine--what we now refer to as nano-medicine--and regenerative
medicine have enormous untapped potential for future space and terrestrial
medical applications. Novel means for drug delivery and nanoscale screening tools
will one day benefit astronauts venturing to Mars and places beyond, while the
space laboratory will foster advances in nanotechnologies for diagnostic and
therapeutic tools to help our patients here on Earth. Herein we review a series
of nanotechnologies and selected regenerative medical approaches and highlight
key areas of ongoing and future investigation that will benefit both space and
terrestrial medicine. These studies target significant areas of human disease
such as osteoporosis, diabetes, radiation injury, and many others.
PMID- 23156090
TI - Differential response of the gastrocnemius and soleus muscles of rats to chronic
hypobaric hypoxia.
AB - BACKGROUND: The hypothesis of the present study is that the occurrence of
oxidative stress with exposure to chronic hypobaric hypoxia will be different in
the gastrocnemius and soleus muscles as these two muscles differ in their fiber
types. METHODS: Male Sprague-Dawley rats were divided into seven groups (I, II,
III, IV, V, VI, VII). Groups I-V were exposed to an altitude of 25,000 ft (7620
m) for 0, 3, 7, 14, and 21 d, respectively. Group VI and VII were given curcumin
orally and exposed to an altitude of 25,000 ft (7620 m) for 0 and 14 d,
respectively. On completion of exposure, the soleus and gastrocnemius muscle were
removed and used for various estimations. RESULTS: Maximum changes were observed
in 14-d exposed gastrocnemius muscle (GM) as compared to soleus muscle (SM).
Lipid peroxidation (nmol x g(-1) of muscle) was higher in GM than SM in 14-d
exposed rats (43.05 +/- 2.96 vs. 27.4 +/- 2.35, respectively). Similarly
significant increases were observed in free radicals and protein carbonyl on
exposure to hypobaric hypoxia. We also observed depletion of the antioxidant,
reduced glutathione, in the exposed rats as compared to the control group. A
significant reduction of 26% was observed in total protein of the GM as compared
to a reduction of 13% in the SM. Myofibrillar proteins were also significantly
decreased in the exposed groups. DISCUSSION: Hypobaric hypoxia affects different
hind limb muscles differentially and the response of each muscle varies as a
function of time. Gastrocnemius muscle is more vulnerable to hypobaric hypoxia
induced oxidative stress in comparison to soleus muscle.
PMID- 23156091
TI - Changes in central corneal thickness, intraocular pressure, and
oxidation/antioxidation parameters at high altitude.
AB - BACKGROUND: The authors aimed at investigating ophthalmological changes at high
altitude and correlating this with blood oxidation/antioxidation parameters.
METHODS: There were 40 volunteers who participated in the study. Initial
ophthalmological examinations were performed at 3543 ft (1080 m) and repeated on
the following day after the participants climbed to an altitude of 9186 ft (2800
m) on Mt. Erciyes, Turkey. Venous blood samples were taken at both altitudes to
evaluate total oxidative system (TOS) and antioxidative system (TAS) levels.
RESULTS: IOP-right eyes at 3543 ft (1080 m) was 13.23 +/- 0.43 mmHg and
significantly increased to 14.45 +/- 0.56 mmHg at 9186 ft (2800 m). LOP-left eyes
at 3543 ft (1080 m) was 13.50 +/- 0.44 mmHg and increased to 14.13 +/- 0.54 mmHg
at 9186 ft (2800 m) (P = n.s.). Central corneal thickness (CCT) of the right eyes
was 540.98 +/- 4.34 microm at 3543 ft (1080 m) and significantly increased to
549.73 +/- 4.59 microm at 9186 ft (2800 m). CCT of the left eyes was 542.13 +/-
29.01 microm at 3543 ft (1080 m) and significantly increased to 547.23 +/- 4.59
microm at 9186 ft (2800 m). Spherical equivalent refraction of right or left eyes
did not show any significant changes. TOS at 3543 ft (1080 m) was 5.33 +/- 0.76
micromol H2O2 equiv/L and significantly increased to 7.55 +/- 0.82 micromol H2O2
equiv/L at 9186 ft (2800 m). TAS at 3543 ft (1080 m) was 2.45 +/- 0.12 micromol
H2O2 equiv/L and decreased to 2.22 +/- 0.08 micromol H2O2 equiv/L (P = n.s.) at
9186 ft (2800 m). There was a positive correlation between TAS and LOP at 9186 ft
(2800 m). CONCLUSION: Increased CCT can be related to stromal edema caused by
hypoxia's effect on corneal endothelial function. Although TOS increased at high
altitude, TAS did not show any parallel increase. Since this was nonacclimatized
climbing, the antioxidant system could not have reached sufficient levels to
counterbalance the observed oxidant stress.
PMID- 23156092
TI - Ligustrazine and the contractile properties of soleus muscle in hindlimb-unloaded
rats.
AB - BACKGROUND: In this study we investigated the effects of different dosages of
ligustrazine (tetramethylpyrazine, Tmp) on soleus function and
sarco(endo)plasmatic reticulum Ca(2+)-ATPase (SERCA) activity in 14-d hindlimb
unloaded (HU) rats. METHODS: Female Sprague-Dawley rats were randomly divided
into 4 groups (8 rats in each group): synchronous control (CON); HU plus
intragastric water instillation (HU-W); HU plus different dosages of instilled
Tmp (high: 42.53 mg x kg(-1), HU-TmpH; low: 21.15 mg x kg(-1), HU-TmpL). Muscle
contraction force was examined in the soleus muscle. SERCA activity was assayed
according to the released inorganic phosphate content. RESULTS: As expected, in
HU-W, soleus peak twitch tension (Pt), peak tetanic tension (P0), time to 50%
peak tension (TP50), time to peak tension (TPT), time from peak tension to 50%
relaxation (RT50), and SERCA activity decreased, all compared with CON. HU-TmpH
Pt and P0 values were 179% and 90% above HU-W, and 187% and 124% above HU-W in HU
TmpL, respectively. TP50 and TPT values were 148% and 80% slower than HU-W with
HU-TmpH and 95% and 32% in the HU-TmpL group, respectively. RT50 was slower than
HU-W by 21% in HU-TmpH; SERCA activity elevated by 56% with HU-TmpH and by 72%
with HU-TmpL. CONCLUSIONS: Ligustrazine may alleviate the decrease of muscle
contractile force and increase of shortening velocity in atrophied soleus,
possibly by means of elevated sarcoplasmic reticulum Ca(2+)-ATPase activity.
PMID- 23156093
TI - Electrocardiographic abnormalities in medically screened military aircrew.
AB - BACKGROUND: The European Society of Cardiology (ESC) recently published its
updated recommendations for electrocardiogram (ECG) interpretation in athletes.
It distinguishes ECG changes related to physical training (group 1 abnormalities)
from training-unrelated changes (group 2) which may represent underlying
electrical and structural heart disorders implicated in exercise related sudden
cardiac death. This study sought to prospectively apply the ESC screening
criteria to a large cohort of screened military aircrew. METHODS: This was a
prospective observational study. The 12-lead ECGs of 868 consecutively evaluated
healthy aircrew were analyzed for the presence of ESC-defined group 1 and 2
abnormalities. RESULTS: The average age was 39.6 (11.2) yr (95.4% male). Overall,
402 (46.3%) of ECGs could be classified as entirely normal. However, 466 ECGs
(53.7%) were abnormal. Group 1 abnormalities were identified in 400 (46.1%)
persons with 66 (7.6%) persons classified as having group 2 abnormalities. The
most commonly identified group 1 ECG changes were sinus bradycardia (32.5%),
early repolarization (11.8%), and isolated voltage criteria of left ventricular
hypertrophy (10.1%). The most commonly noted group 2 abnormalities were left-axis
deviation/left anterior hemiblock (2.4%), T-wave inversion (1.6%), and ST-segment
depression (1.3%). Prolongation of the QTC > 0.46 s was observed in 0.69% of
ECGs. CONCLUSIONS: The vast majority of ECGs performed in military aircrew could
be classified as representing likely normal physiological changes. Training
unrelated ECG changes, suggestive of possible genuine cardiac pathology, were
observed in only a minority of persons who should be considered for further
investigation.
PMID- 23156094
TI - Risk factors for musculoskeletal injuries for soldiers deployed to Afghanistan.
AB - PURPOSE: This study determined injury incidence and examined the association
between musculoskeletal injuries and potential intrinsic and extrinsic risk
factors. METHODS: This retrospective cohort study involved a survey of 593
volunteers from two battalions of a Stryker Brigade Combat Team upon completion
of a 12-mo deployment to Afghanistan. The survey included questions on physical
characteristics, work duties, equipment worn, fitness training, and injuries
experienced during the deployment. RESULTS: Of the surveyed soldiers, 45%
sustained an injury during the deployment. Total injuries resulted in 5049 d of
limited duty, an average of 8.5 d per injury. The body regions with the largest
numbers of injuries were the low back (17.4%), knee (12.7%), and shoulder
(10.0%). The majority (65%) of injuries occurred while working. The most frequent
activities soldiers reported as the cause of injury were lifting and carrying
(9.8%), dismounted patrolling (9.6%), and physical training (8.0%). Older age,
higher enlisted rank, female sex, months deployed, more time spent standing,
longer strength training sessions, heaviest load worn, and heavier or more
frequent lifting tasks were all associated with injury. DISCUSSION: Tasks
requiring physical energy expenditure such as load carriage, lifting, or standing
resulted in an increased risk of musculoskeletal injury in this study.
Lifting/carrying, dismounted patrols, and physical training were associated with
26% of musculoskeletal injuries. The weight of loads carried and lifting may be
exceeding the work capacity of the soldiers, resulting in injury. These injuries
in turn limit available work days for military units, reducing combat power.
PMID- 23156096
TI - Clothing buoyancy and underwater horizontal swim distance after exiting a
submersed vehicle simulator.
AB - BACKGROUND: Winter road workers, who drive heavy vehicles over ice-covered
waterways, are at risk for ice failure, vehicle submersion, and subsequent
drowning in frigid water. Although some jurisdictions require these workers to
wear flotation clothing, there are concerns that, following an underwater exit in
fast-moving water, increased clothing buoyancy may reduce ability to swim against
the current to safely return to the ice opening. METHODS: Using a simulator in a
swimming pool (3.7 m deep, 28 degrees C), 11 volunteers (5 women) were submersed
8 times each to test the effects from both an Upright and an Inverted position of
a normal nonflotation winter jacket (Control), a flotation Jacket, a flotation
Overall, and a personal inflatable vest which was inflated (Inflated Vest) on
underwater horizontal swim distance. Subjects also rated exit difficulty and
impedance, psychological stress, and thermal comfort. RESULTS: Compared to
Control, Jacket, and Overall, the Inflated Vest generally increased exit
difficulty, escape impedance, and psychological stress, while greatly decreasing
the ability to swim horizontally underwater before reaching the surface (Control,
6.1 m; Jacket, 5.0 m; Overall, 3.4 m; and Inflated Vest only 1.4 m). Swim
distance with the Overall was also significantly shorter than Control, but not
Jacket. DISCUSSION: Flotation clothing (either Jackets or Overalls) is
recommended for vehicle travel on ice because they do not impede underwater exit
from a vehicle and allow significant horizontal underwater swim distance. An
inflatable vest is not recommended because inappropriate premature inflation
could increase exit impedance and decreased underwater swim distance.
PMID- 23156095
TI - Forehead-mounted reflectance oximetry for in-cockpit hypoxia early detection and
warning.
AB - INTRODUCTION: Effective hypoxia-related mishap prevention relies upon aircrew
rapid recognition of hypoxia symptoms. The objectives of this experiment were
twofold: to compare the effectiveness of a forehead-mounted reflectance oximeter
and finger-mounted pulse oximeter for application in a hypoxia early warning
detection system, and to determine whether the forehead-mounted sensor could be
placed within an aviation helmet. METHODS: Subjects donned an aviation flight
mask and were instrumented with a forehead reflectance oximeter, a finger pulse
oximeter, a blood pressure cuff, and a skin temperature sensor. Following
instrumentation, subjects breathed ambient air for 10 min through the Reduced
Oxygen Breathing Device (ROBD) to allow for acclimation. The baseline period was
followed by one of two counterbalanced ascent profiles used to model rapid
exposures to altitude. Data were collected at 1 Hz from both sensors for the
duration of the protocol. RESULTS: Analyses indicated an exceptionally strong
agreement between the forehead and finger sensors at all ranges of desaturation.
The sensitivity data revealed that the forehead sensor was significantly faster
when responding to rapid changes in SpO2 than the finger. The sensor was
successfully integrated inside the helmet; however, once donned by the subject,
there was considerable artifact due to pressure fluctuations. DISCUSSION: While
these data may seem to suggest that the forehead sensor is accurate and sensitive
to altitude induced changes in SpO2, major drawbacks exist for the technology
utilized in the current study. Significant improvements aimed at diminishing
noise, curbing motion artifact, and improving reliability are required to reduce
errant measurements.
PMID- 23156097
TI - Acute neurological symptoms during hypobaric exposure: consider cerebral air
embolism.
AB - Cerebral arterial gas embolism (CAGE) is well known as a complication of invasive
medical procedures and as a risk in diving and submarine escape. In the
underwater environment, CAGE is caused by trapped air, which expands and leads to
lung vessel rupture when ambient pressure decreases during ascent. Pressure
decrease also occurs during hypobaric activities such as flying and, therefore,
CAGE may theoretically be a risk in hypobaric exposure. We reviewed the available
literature on this subject. Identified were 12 cases of CAGE due to hypobaric
exposure. Based on these cases, we discuss pathophysiology, diagnosis, and
treatment of CAGE due to hypobaric exposure. The low and slow pressure decrease
during most hypobaric activities (as opposed to diving) account for the low
incidence of CAGE during these exposures and suggest that severe air trapping
must be present to cause barotrauma. This is also suggested by the large
prevalence of air filled cysts in the case reports reviewed. We recommend
considering CAGE in all patients presenting with acute central neurological
injury during or shortly after pressure decrease such as flying. A CT scan of
head and chest should be performed in these patients. Treatment with hyperbaric
oxygen therapy should be initiated as soon as possible in cases of proven or
probable CAGE.
PMID- 23156098
TI - +Gz-induced spinal symptoms in fighter pilots: operational and individual
associated factors.
AB - INTRODUCTION: Neck pain in fighter pilots has been studied by several air forces
and found to be relatively common. The aim of this project was to study the
incidence, characteristics, possible associated causative factors, and
operational impact of neck pain in Royal Norwegian Air Force (RNoAF) fighter
pilots. METHODS: The study was designed as a retrospective anonymous
questionnaire survey, collecting data on age, aircraft type, flying hours, and
physical activity. Any experience of spinal symptoms related to flying was
included, as well as detailed questions on operational factors. Estimates
regarding how neck symptoms influenced flying performance were established using
visual analogue scales (VAS). Pilots also described their own in-flight
techniques to avoid neck symptoms. RESULTS: Of respondents, 72% had experienced
neck pain in relation to flying, while 35% had experienced back pain. Of these
episodes, 93% were related to neck rotation. Mean G level for acute incidents of
in-flight pain was 6.7 G. Total training time is on average higher in pilots who
have no neck pain compared to those who have had neck pain events in the last 12
mo; the mean training time being 3.9 h in the "no pain-group" vs. 2.7 h in the
"pain group". "Checking six" was the most affected in-flight function.
DISCUSSION: New technologies such as night-vision goggles and helmet-mounted
displays increase helmet weight, thereby adding a higher strain to the neck even
in moderate G environments. More research on specific prevention strategies is
warranted in order to improve the in-flight working environment of fighter
pilots.
PMID- 23156099
TI - Superior vestibular dysfunction in severe decompression sickness suggests an
embolic mechanism.
AB - BACKGROUND: Both nitrogen bubble embolism and the difficulty of inner ear tissues
to wash out nitrogen have been discussed as possible reasons for the selective
vulnerability of the inner ear to decompression illness. This case report
suggests that nitrogen bubble embolism plays a crucial role in the pathogenesis
of inner ear lesions in decompression accidents. CASE REPORT: The current
patient, a 48-yr-old male dive master, suffered a severe decompression illness
with vertigo as the only residual symptom. At the 1-mo follow-up, neuro
otological evaluation revealed a selective lesion of the superior vestibular
division of the left labyrinth with normal functioning inferior vestibular
division. At vestibular testing, there was no caloric response from the affected
left ear, and the head impulse tests for the lateral and anterior semicircular
canal were also impaired. Tests of vestibular evoked myogenic potentials (VEMP)
showed divergent results. Ocular VEMP in response to left ear stimulation were
absent, whereas the cervical VEMP were completely symmetrical and normal. Thus,
the lesion profile implies a partial vestibular loss selectively affecting the
superior vestibular division of the inner ear. DISCUSSION: The most likely
explanation for such a selective injury seems to be bubble microembolism coupled
with both the specific anatomy of this terminally supplied subunit, and with the
slow nitrogen wash-out of the vestibular organ.
PMID- 23156100
TI - Airborne visibility indicator system.
PMID- 23156101
TI - You're the flight surgeon: sudden onset of flying phobia.
PMID- 23156102
TI - You're the flight surgeon: ocular hypertension.
PMID- 23156103
TI - This month in aerospace medicine history.
PMID- 23156104
TI - Meningitis mess. The trouble with custom-made drugs.
PMID- 23156105
TI - [Formation of therapeutic group of casualties in local wars and armed conflicts].
AB - The necessity of improvement of the therapeutic care organization in the RF Armed
Forces is dictated by the existing military threats. Conflicts between states or
within a single country along with inefficiency of diplomatic, social and
political efforts may lead to armed conflicts or local wars. Analysis of medical
support results shows the consistent prevalence of therapeutic group of
casualties in the overall structure of medical losses. 35-50% of all sanitary
losses is accounted for by somatic diseases. Moreover, their structure is similar
to the structure of the army's peacetime morbidity rate. Respiratory diseases
head the list of somatic diseases in military personnel. Next--diseases of the
digestive and circulatory systems. One of the most important tasks for physicians
in wartime is early diagnosis and treatment of visceral pathology in the wounded.
An additional point is that the use of tactical nuclear weapons during the armed
conflict or local war cannot be completely excluded. There is also a real risk of
nuclear and chemical facilities damage, with consequences that are comparable to
the use of nuclear or chemical weapons. Thus, in the course of armed conflict or
local war, military physicians can meet all possible therapeutic spectrum of
pathology: from visceral pathology of peace and wartime to combat related
therapeutic pathology.
PMID- 23156106
TI - [Organizational and methodological approaches to the medical rehabilitation of
the wounded from the consequences of combat trauma in the upper limb in
rehabilitation center].
AB - This article discusses the possibility of optimizing the organizational and
methodological approaches to the medical rehabilitation of the wounded from the
consequences of combat trauma of the upper extremities in rehabilitation center.
Clearly the implementation of organizational measures and technologies optimized
medical rehabilitation, restoration of function provided the injured extremity:
total of 152 (64%) injuries, partial in 26 (11%) injuries, as well as the
stability of long-term results. Optimization using the traditional methods of
treatment (biomehanoterapiya, chiropractic, massage, acupuncture, integrated
technology) has increased the effectiveness of medical rehabilitation at 35%.
PMID- 23156107
TI - [Analysis of the health of citizens of military age in Orenburg region].
AB - Results of medical examination of citizens of military age living in the Orenburg
region for a decade are given. Noted that over the study period in the region
have been positive changes: performance fitness for military service on health
increased from 62.9% in 2000 to 67.7% in 2009 and projected to the positive
dynamics in 2020 also marked improvement in physical fitness and the citizens of
military age, a significant reduction in the number of recruits with poor and low
power.
PMID- 23156108
TI - [Directions of interdepartmental interaction in case of delivery of health care
for injured in emergency situations in stationing sites of navy].
AB - In points basing of navy will remain probability of emergence of emergency
situations which is connected with existence of the enterprises of the industry
and objects of navy. As a result of emergency situations in places of basing of
navy discrepancy of prospective sanitary losses to possibilities of forces and
means of a health service of fleet that demands interaction with health services
of other ministries and departments is probable. Criterion of need of interaction
is the ratio of quantity struck and possibilities of a health service of navy.
Plans of interaction of a health service of fleet with medical institutions of
other departments should provide options of use of available forces and means of
medical institutions in garrisons for joint assistance struck in an emergency
situation. The questions solved during interaction should become: radiation,
chemical, biological survey; allocation of forces and means for rendering of
medical care; use of sanitary transport; organization of sanitary processing,
etc.
PMID- 23156109
TI - [Analysis of frequency and structure of cerebrovascular diseases in servicemen
during the military physician expertise].
AB - Analysis of the results of medical inspection of soldiers under contract taken
place in 2005-2009 is given. In 48.9% of cases was revealed diseases of blood
circulatory system. In patients with cardiovascular events in 42.2% of cases
different forms of cerebrovascular diseases were diagnosed. It shows high level
of these diseases and its early progression among the servicemen. According to
the authors, specific peculiarities of intensive military service provide the
early progression of diseases. In such a case, presence of cerebrovascular
diseases influences on expert decisions about professional suitability of
servicemen for some military specialties including the level of suitability for
military service.
PMID- 23156110
TI - [About the causes of inveterate cystitis in young women].
AB - 16 female patients,aged 28.6 +/- 3.2 years, with recrudescent inveterate cystitis
were examined for the purpose of improvement of treatment of chronic cystitis.
The examined patients noted relapse of disease after sex intercourse. Spectrum of
diagnosed uropathogens in female patients corresponds to the structure of
bacterio from urina taken after prostate milking and prostatic fluid of patients'
intercourse partners. The given uropathogens also corresponds to the structure of
contagium of urinary tract in young men. Connection between urogenital biotope
and biotope of prostate as a vessel of persistence infection is related.
Recrudescent inveterate cystitis in young women may be result from latent
inveterate bacteritic prostatitis in their intercourse partners. Effectiveness of
treatment and prophylaxis of recrudescence of inveterate cystitis in young women
depends on timely diagnostics, treatment, and prophylaxis of inveterate
bacteritic prostatitis in their intercourse partners.
PMID- 23156111
TI - [Diagnostics and treatment of patients with sarcoidosis in multidisciplinary
military hospital].
AB - The authors analyzed the methods of diagnostics, clinical peculiarities of
sarcoidosis in different groups of patients, treated in multidisciplinary
military hospital. The authors also analyzed the possibility of estimation of
optimum diagnostic and medical tactics on the basis of prospective observation
after patients with morphologically confirmed sarcoidosis, treated in pulmonary
department of the Main Military Clinical Hospital n. a. N.N. Burdenko.
PMID- 23156112
TI - [Peculiarities of adaptation of servicemen service].
AB - Review of issues about the adaptation of servicemen in the process of military
service is presented. Characteristics of military service, conditions and levels
of official-military activity, peculiarities of adaptation, factors providing
progression of psychosomatic diseases and dysaptation, concept "occupational
health" are considered.
PMID- 23156113
TI - [Analysis of infringements of exchange processes in combatatnts with
psychosomatic disorders in the period after participation in operations].
AB - Analysis of clinical and biochemistry blood test parameters was conducted. It was
revealed that metabolic disorders with predomination of catabolic reactions are
typical for combatatnts who took part in military actions. So, the blood serum
glucose value in the patients group is higher than in the control group. Military
men with psychosomatic disorders are characterized by the decrease of cholesterol
and triglycerides. The obtained data is supported by the results of model
analysis of posttraumatic stress disorders in animals.
PMID- 23156114
TI - [Visual illusions and moving horizon].
AB - Results of psychological "additional investigation" of the crash of Boeing-737,
"Aeroflot-Nord" on 14.09.2008 near Perm are presented. 37 pilots from the one of
the leading airline companies sensed the attitude and rolling out the aircraft to
the forward flight under the moving horizon with straight display of bank and
tangage (view from the aircraft to the ground) in model conditions. 29 pilots
(78.4%) made a mistake at determining the roll direction and tangage, they made a
mistake at determining the roll direction 61 times (16.4%) and 44 times at
determining the tangage direction, in other words they confused left and right
bank and also nose-up and nose-down. Visual illusions of mobility of space and
handling of ground (instead of aircraft) during the flight were revealed in
pilots. These illusions may be the important cause of the following crashes. The
necessity of "back" faultless display of bank in all aircrafts of civil aviation
and development of computer complex for training of visual spatial orientation is
proved.
PMID- 23156115
TI - [About the fitness to work of sailors during the campaign of surface vessel in
conditions of Polar Region].
AB - The authors analyzed functional condition of organism and peculiarities of
fitness to work of sailors with the help of physical load during the campaign of
surface vessel of special assignment in conditions of Polar region with
complicated complex of unfavourable factors of environment. Index of physical
efficiency and regulation of heart rhythm of the personnel in dynamic of 2-month
campaign are analyzed. Connection between this data and regular sanitary
exercises is explored. Influence of physical load as an independent training and
in special program is estimated. The authors thought that the criterion of
optimality is preservation of initial level of efficiency during the campaign. It
is proved that wrong-running independent training may cause worsening functional
condition of the organism.
PMID- 23156116
TI - [Medical supply of the Russian army during the Patriotic War in 1812].
AB - The article is devoted to the 200th anniversary of the victory of the russian
weapon in the Patriotic War in 1812. Russian military medics lended a weighty
contribution to destruction of the strongest Napoleonic army. Together with
russian soldiers they suffered woes and hardships, accompanied Russian soldiers
not only in moments of victories but also in the most hard moment, saving lives
of wounded and illed, soldiers and civil population. Structure of medical service
of the Russian Army, types of delivery of health care, some epispdes of the work
of military medics are described.
PMID- 23156117
TI - [Act of bravy of Surgeon in ordinary to the King Yustus Loder].
AB - Yustus Christian (in russian transcription Christian Ivanovich) Loder (1753-1832)
studied in Gottingen University, where in 1777 defended degree of Doctor of
Medicine and Surgery. The article is devoted to his activity in organisation of
delivety of the health care to the wounded during the Patriotic War in 1812 year.
From September 1812 to May 1813 30 126 patients were treated in the hospitals
controlled by Loder, 23 413 stepped back into the ranks, in other words almost
77%. 2096 patients died (7%). Loder was against so called early amputation widely
propogated by surgeon-in-chief of French army D.Zh.Larrey as the only life
preserver.
PMID- 23156118
TI - [Hospital schools during the Russian-Turkish War 1735-1739].
AB - In 1733 besides the school before the Moscow hospital also three hospital schools
were open before Saint-Petersburg terrestrial and admiralty hospitals and before
the hospital in Kronshtadt. The process of transfer of students from schools to
army was the most intensive during the military conflicts with that is rich
Russian history in XVIII century. According to documents, presented in the
article, during the Russian-Turkish War in 1735-1739 hospital schools worked
active and discharged a task of recruiting of medical service of the Russian
Army. The most important precondition was basis of military-medical education
grounded by Peter at the beginning of XVIII century.
PMID- 23156119
TI - Effect of wheat flour fortified with sodium iron EDTA on urinary zinc excretion
in school-aged children.
AB - BACKGROUND: Foods fortified with sodium iron ethylenediaminetetraacetate
(NaFeEDTA) have been shown to improve iron status in children, but little is
known about the effect of this salt on urinary zinc excretion, particularly in
children. This is particularly relevant, since zinc deficiency is known to limit
growth and development in young children. OBJECTIVE: To determine the effect of
NaFeEDTA-fortified wheat flour on urinary zinc excretion. METHODS: This study was
a part of a randomized, controlled trial that was carried out among 6- to 13-year
old iron-depleted schoolchildren (n = 179) who had received either a NaFeEDTA
fortified wheat meal (iron group) or an identical control meal without added iron
(control group) for a period of 7 months. Urinary zinc concentration was assessed
at the end of the intervention period by spot urine samples. RESULTS: Iron status
in the iron group was significantly improved according to measurements of
hemoglobin and serum ferritin (p < .001). However, there was no significant
difference in urinary zinc excretion between the iron group (median, 38.4
microg/dL; 25th-75th percentiles, 18.2-67.1 microg/dL) and the control group
(median, 33.1 microg/dL; 25th-75th percentiles, 12.4-54.2 microg/dL).
CONCLUSIONS: Iron fortification of foods with NaFeEDTA does not affect urinary
zinc excretion in children.
PMID- 23156120
TI - Iron-fortified wheat flour and iron deficiency among women.
AB - BACKGROUND: Iron deficiency is estimated to impact more than 1.6 billion
individuals worldwide, affecting child, maternal, and perinatal mortality. Iron
supplementation, fortification, and dietary diversification are strategies to
reduce the prevalence of iron deficiency. However, there are relatively few
studies demonstrating the effectiveness of iron-fortified wheat flour as an
intervention. OBJECTIVE: To assess the relationship between average monthly per
capita household consumption of iron-fortified wheat flour and iron deficiency
among women of childbearing age in Oman. METHODS: Data were obtained from the
National Micronutrient Status and Fortified Food Coverage Survey, 2004. Iron
deficiency status was compared between women living in households with a monthly
per capita consumption of iron-fortified wheat flour of 1 kg or more and women
living in households with a monthly per capita consumption of iron-fortified
wheat flour of less than 1 kg. The analyses excluded women with elevated or
unknown levels of C-reactive protein and controlled for characteristics of the
women and household demographics. RESULTS: Consumption of iron-fortified wheat
flour was associated with a lower prevalence of iron deficiency among women in
our sample (adjusted odds ratio, 0.60), after controlling for age, employment
status, marital status, intake of iron or multivitamin supplements, self-reported
presence of a blood disorder, household income, educational level of head of
household, and family size. CONCLUSIONS: These results suggest that women in our
study living in households with a greater consumption of iron-fortified wheat
flour have a lower prevalence of iron deficiency; however, additional study is
needed.
PMID- 23156121
TI - Vegetable oil of poor quality is limiting the success of fortification with
vitamin A in Egypt.
AB - BACKGROUND: Fortification of vegetable oil with vitamin A is considered a cost
effective and simple to implement strategy, but the stability of vitamin A
remains a limiting factor. To account for losses of vitamin A, oil producers add
an overage. Optimizing the amount of this overage can result in considerable
savings for industry and government while ensuring a supply of adequately
fortified oil to consumers. OBJECTIVES: To estimate vitamin A losses in oil with
different chemical characteristics. METHODS: Samples of fortified oils with
different chemical characteristics were collected from two Egyptian companies
(oil A and B) and stored for 1 month. Vitamin A levels were analyzed periodically
during storage to determine losses over time, and peroxide values were
determined. RESULTS: Fortified oil B, with a high peroxide value (5.8 mEq/kg),
exposed to sunlight had significantly higher losses of vitamin A after 4 weeks
than fortified oil A, with a low peroxide value (0.4 mEq/kg): 31.1% vs. 19.7% (p
< .001), respectively. In semidark conditions, the vitamin A losses after 4 weeks
in fortified oil B and fortified oil A were significantly different: 26.1% and
0.7% (p < .001), respectively. In an accelerated storage test, the vitamin A loss
in 8 days was 48.3% for fortified oil B and 4.2% for fortified oil A (p < .001).
CONCLUSIONS: This study shows a significant effect of peroxide level (one
indicator of the quality of oil) on the stability of vitamin A, regardless of
storage conditions. To optimize and sustain vitamin A levels in fortified oil,
governments and industries should minimize the peroxide level to less than 2
mEq/kg at production.
PMID- 23156122
TI - Effects of third trimester counseling on pregnancy weight gain, birthweight, and
breastfeeding among urban poor women in Bangladesh.
AB - BACKGROUND: Maternal malnutrition and poor gestational weight gain are the most
important causes of low birth weight and high rates of newborn mortality.
OBJECTIVE: To assess the effects of nutrition counseling in the third trimester
of pregnancy on maternal weight gain, birth weight of newborn, and breastfeeding
practices. METHODS: This was a longitudinal experimental study with nutrition
intervention for a period of 3 months. One hundred fifteen women (57 in the
intervention group and 58 in the comparison group) who were visiting the Maternal
and Child Health Training Institute at 6 months of pregnancy were randomly
selected. The intervention group was given nutrition education twice in the first
month and once a month for the next 2 months before delivery; the comparison
group received routine hospital advice on food intake, immunization, personal
hygiene, and breastfeeding. The women were weighed monthly up to delivery, the
newborn infants' birth weights were measured within 24 hours after delivery, and
breastfeeding practices were observed 1 month after delivery. RESULTS: Women in
the intervention group gained 1.73 kg more weight during the third trimester than
women in the comparison group (5.61 vs. 3.88 kg, p < 0.001). The mean birthweight
of babies of women in the intervention group was 0.44 kg greater than that of
babies of women in the comparison group (2.86 vs. 2.42 kg, p < 0.001). In the
intervention group, 10.5% of babies were born with low birthweight, compared with
48.3% of the babies of women in the comparison group (p < 0.001). In the
intervention group, 75.4% of mothers initiated breastfeeding within 1 hour after
birth, compared with 34.5% of mothers in the comparison group (p < 0.001).
CONCLUSIONS: Nutrition education only during the third trimester improved weight
gain during pregnancy, reduced 78% of low birth weight, and improved
breastfeeding practices.
PMID- 23156123
TI - Performance of iron spot test with Arabic bread made from fortified white wheat
flour.
AB - BACKGROUND: The iron spot test (IST) is a simple qualitative technique for
determining the presence of added iron in fortified flour. IST performance in
bread has never been investigated. If found to perform well, the IST has the
potential to provide a field-friendly method for testing bread and thus support
the monitoring and evaluation of flour fortification programs. OBJECTIVE: To
assess the performance of the IST in Arabic bread made from white wheat flour.
METHODS: Bread samples were collected from 1,737 households during a national
micronutrient survey in Jordan. A subsample of Arabic bread (n = 44) was
systematically selected for testing by both the IST and spectrophotometry
(criterion reference). Performance measures (sensitivity, specificity, and
positive and negative predictive values) were calculated using five cutoffs to
define the presence of added iron, including > or = 15.0 ppm (approximate level
of natural iron in Arabic bread) and four additional cutoffs based on test
performance. RESULTS: The iron contents of samples testing negative by IST ranged
from 10.4 to 18.4 ppm, with one outlier at 41.0 ppm, which was excluded from
subsequent analyses. The iron contents of samples testing positive by IST ranged
from 16.1 to 38.4 ppm. With the exception of negative predictive values for the
two lowest cutoffs (> or = 15.0 and > or = 16.1 ppm), all performance measures
exceeded 83.3%. CONCLUSIONS: These results show promise for the IST as an
inexpensive, field-friendly method for testing bread that could have a useful
role in the monitoring and evaluation process for flour fortification programs.
PMID- 23156124
TI - Cost analysis of community-based daily and weekly programs for treatment of
moderate and mild wasting among children on Nias Island, Indonesia.
AB - BACKGROUND: Ready-to-use food in the form of biscuits (RUF-Nias biscuit) was
locally produced for rehabilitation of moderately and mildly wasted (weight-for
height z-score > or = -3 to < -1.5 SD) children on Nias Island, Indonesia. Daily
programs were performed in semiurban settings, and weekly programs took place in
rural areas. OBJECTIVE: To analyze the cost of daily and weekly distribution and
supervision of RUF-Nias biscuit programs. METHODS: The costs of the daily and
weekly programs were derived from the financial report and interviews with
program implementers and participating households. Costs were calculated on the
basis of total rehabilitation costs per child per day required to achieve a
target weight-for-height z-score > or = -1.5 SD in daily and weekly programs.
RESULTS: Institutional costs to the implementing organization were similar for
both programs (approximately US $4 per child per day). The daily programs
resulted in a significantly higher proportion of recovered children (78.6% vs.
65.4%) and higher weight gain (3.7 vs. 2.2 g/kg/day) than the weekly programs.
About 6% to 7% of the total cost of the programs was accounted for by locally
produced RUF-Nias biscuits. The social cost borne by the community for the weekly
programs was about half that for the daily programs. CONCLUSIONS: The daily
programs achieved better results for the implementing organization than the
weekly programs; however, the weekly programs were preferred by the community
because of the lower time constraints and the lower opportunity cost of time. The
willingness of community and household members to invest their time in more
intensive activities in the daily programs led to better program outcomes.
PMID- 23156125
TI - Evaluation of iodine content in table salt consumed in Democratic Republic of
Congo.
AB - BACKGROUND: DR Congo has adopted universal salt iodization to reduce disorders
due to iodine deficiency. Since 1994, only iodized salt can be imported, but
there is currently no routine monitoring of the iodine content of distributed
salt. It is therefore unclear if iodine deficiency remains a health problem,
particularly in pregnant women. OBJECTIVE: To evaluate the iodine content of salt
in households of pregnant women in Lubumbashi. METHODS: We conducted a survey of
the iodine content of salt consumed by 375 women presenting at prenatal
consultations in three socially different areas of Lubumbashi: urban, semiurban,
and rural. The women were questioned about where they purchased salt, how it was
packaged, and how they stored the salt, and each woman provided a sample of salt
for determination of its iodine content by the iodometric method. RESULTS: Most
women (84.3%) bought salt in the public markets, mainly in bulk (93.6%); 80.0%
stored salt in plastic boxes. The median iodine content was 27.5 ppm (IQR, 16.0
38.1) in urban areas, 19.0 ppm (IQR, 7.4-31.7) in semiurban areas, and 20.1 ppm
(IQR, 5.3-31.7) in rural areas. The iodine content was less than 15 ppm (minimum
threshold) in 36.3% of samples, including 13.9% without any detectable iodine.
The iodine content was above 40 ppm (maximum limit) in 18.9% of samples. Only
44.8% of salt samples had adequate iodine content. CONCLUSIONS: The population of
Lubumbashi remain at risk for hypothyroidism and hyperthyroidism. A effective and
regular system for the control of iodin content in distributed salt is needed in
DR Congo.
PMID- 23156126
TI - Stay ahead of the pack.
PMID- 23156127
TI - Practice assessment: what's in it for me?
PMID- 23156128
TI - Cloned notes: the time is ripe to review your practices. Office of the inspector
general initiates E&M services review.
PMID- 23156129
TI - Tackling population health management: it boils down to HIT. MGMA-ACMPE members
get exclusive look at industry research.
PMID- 23156130
TI - What drives physician salaries?
PMID- 23156131
TI - Who's in the driver's seat? Physician compacts help you steer your practice.
PMID- 23156132
TI - Seen the new hybrids. A blend of concierge and traditional practice models
emerges.
PMID- 23156133
TI - Schedule tests in advance for higher efficiency and happier patients.
PMID- 23156134
TI - Social media: real life online.
PMID- 23156135
TI - Fair-market value testing.
PMID- 23156136
TI - Working together: keys for successful partnerships with specialists.
PMID- 23156137
TI - Don't let your PDA go MIA.
PMID- 23156138
TI - So many patients, one little form. Association member streamlines patient
scheduling process.
PMID- 23156139
TI - Reach for the stars: learning to see beyond the workday. Lawrence schindler, MHA,
MGMA-aCMPE member, consultant, Apache Junction, Ariz.
PMID- 23156140
TI - Mathematical modeling, spatial complexity, and critical decisions in tsetse
control.
AB - The tsetse fly complex (Glossina spp.) is widely recognized as a key contributor
to the African continent's continuing struggle to emerge from deep economic,
social, and political problems. Vector control, the backbone of intensive efforts
to remove the human and livestock trypanosomosis problem, has been typified by
spectacular successes and failures. There is widespread agreement that integrated
vector control, combined with direct disease treatment and prevention, has to
play a major role in alleviating the tsetse burden in Africa. Mathematical and
computer-based simulation models have been extensively used to try to understand
how best to manage these control efforts. Such models in ecology have been
helpful in giving broad generalizations about population dynamics and control.
Unfortunately, in many ways they have inadequately addressed key aspects of the
fly's biology and ecology, particularly the spatio-temporal variability of its
habitats. These too must factor in any control efforts. Mathematical models have
inherent limitations that must be considered in their use for control programs.
In this review, we consider some of the controversies being debated within the
field of ecology and evolution about the use of mathematical models and
critically review several models that have been influential in structuring tsetse
control efforts. We also make recommendations on the appropriate role that
mathematical and simulation models should play when used for these purposes.
Management programs are often vulnerable to naively using these models
inappropriately. The questions raised in this review will apply broadly to many
conservation and area-wide pest control programs with an ecological component
relying on mathematical and computer simulation models to inform their decisions.
PMID- 23156141
TI - A new low-cost procedure for detecting nucleic acids in low-incidence samples: a
case study of detecting spores of Paenibacillus larvae from bee debris.
AB - American foulbrood, because of its virulence and worldwide spread, is currently
one of the most dangerous diseases of honey bees. Quick diagnosis of this disease
is therefore vitally important. For its successful eradication, however, all the
hives in the region must be tested. This is time consuming and costly. Therefore,
a fast and sensitive method of detecting American foulbrood is needed. Here we
present a method that significantly reduces the number of tests needed by
combining batches of samples from different hives. The results of this method
were verified by testing each sample. A simulation study was used to compare the
efficiency of the new method with testing all the samples and to develop a
decision tool for determining when best to use the new method. The method is
suitable for testing large numbers of samples (over 100) when the incidence of
the disease is low (10% or less).
PMID- 23156142
TI - Effects of soil-applied imidacloprid on Asian citrus psyllid (Hemiptera:
Psyllidae) feeding behavior.
AB - The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Psyllidae), is
one of the most important pests of citrus (Citrus spp.) because of its status as
a vector of Candidatus Liberibacter asiaticus (Las), the bacterium associated
with citrus greening disease. The use of insecticides for vector control is the
primary method of managing the spread of this pathogen. Imidacloprid is an
insecticide commonly applied to the root zone of young citrus trees to provide
systemic protection from pests. The effects of imidacloprid on feeding behavior
of D. citri have not been studied in much detail. The purpose of this study was
to examine the effects of imidacloprid application on feeding behavior of D.
citri and to determine whether use of this systemic insecticide could have any
effect on pathogen transmission by D. citri. A direct current electrical
penetration graph monitor was used to record D. citri feeding behaviors for 12-h
periods on mature and young leaves of imidacloprid-treated and -untreated citrus
seedlings. Overall, compared with untreated plants, the feeding behavior of D.
citri was disrupted on imidacloprid-treated plants via reduction in the number of
probes, as well as durations of average probes, initial stylet contact with
phloem, phloem salivation, and phloem ingestion. The results of this study
demonstrate that soil applications of imidacloprid can reduce the probability of
citrus plants becoming inoculated with Las through a reduction in the number and
duration of phloem salivation events by D. citri. Furthermore, Las acquisition
from infected citrus is greatly reduced as a result of decreased phloem ingestion
by D. citri on imidacloprid-treated plants.
PMID- 23156143
TI - Interspecific interaction between Spodoptera exigua multiple nucleopolyhedrovirus
and Microplitis bicoloratus (Hymenoptera: Braconidae: Microgastrina) in
Spodoptera exigua (Lepidoptera: Noctuidae) larvae.
AB - Baculoviruses and parasitoids are important biological control factors of insects
in integrated pest management. Microplitis bicoloratus Chen (Hymenoptera:
Braconidae: Microgastrina) is a solitary endoparasitoid of beet armyworm,
Spodoptera exigua (Hubner) (Lepidoptera: Noctuidae) larvae. M. bicoloratus
parasitized first to third instars of S. exigua and most effectively parasitized
second instars. The survival rate of parasitoids emerging from S. exigua multiple
nucleopolyhedrovirus (SeMNPV)-infected hosts decreased with increasing SeMNPV
doses at second to fourth instars. In addition, the mortality rate of the host
was > 80% when coinfected with SeMNPV and M. bicoloratus, regardless of virus
doses or the timing of virus treatment. Occlusion body production was
significantly reduced in parasitized hosts. A comparison of host weights showed
that hosts coinfected with SeMNPV and M bicoloratus were significantly lighter
than those infected with SeMNPV alone, suggesting that the decrease in virus
yield resulted from a reduction in larval growth. The viral genome copy number in
parasitized host was significantly lower than that in nonparasitized host at 48
and 72 h postinfection. These results suggest that SeMNPV and M. bicoloratus are
compatible as S. exigua control agents.
PMID- 23156144
TI - Identification and impact of natural enemies of Bactericera cockerelli
(Hemiptera: Triozidae) in Southern California.
AB - Bactericera cockerelli (Sulc) (Hemiptera: Triozidae) is a major pest of potato,
(Solanum tuberosum L.), tomato (Solanum lycopersicum L.), and peppers (Capsicum
spp.). The purpose of our research was to identify and determine the impact of
natural enemies on B. cockerelli population dynamics. Through 2 yr of field
studies (2009-2010) at four different sites and laboratory feeding tests, we
identified minute pirate bug, Orius tristicolor (White) (Hemiptera:
Anthocoridae); western bigeyed bug, Geocoris pallens Stal (Hemiptera:Geocoridae),
and convergent lady beetle, Hippodamia convergens Guerin-Meneville (Coleoptera:
Coccinellidae) as key natural enemies of B. cockerelli in southern California
potatoes, tomatoes, and bell peppers. In natural enemy exclusion cage experiments
in the potato crop and in American nightshade, Solanum americanum Miller, the
number of B. cockerelli surviving was significantly greater in the closed cage
treatments, thus confirming the affect natural enemies can have on B. cockerelli.
We discuss how this information can be used in an integrated pest management
program for B. cockerelli.
PMID- 23156145
TI - Identification of Orius (Heteroptera: Anthocoridae) females based on egg
operculum structure.
AB - Naturally occurring predators of the genus Orius (Heteroptera: Anthocoridae)
often suppress agricultural pests in insecticide-free environments. Knowledge of
Orius species composition in the field is important because species vary in their
biology, prey preference, and ability to suppress pest populations. However,
field-collected Orius bugs are often female biased and the identification of
Orius females may be unreliable and time consuming. Identification of Orius
species based on egg structure may allow easy and nondestructive identification
of females, by inspecting the eggs they deposit, and identification of species
that reproduce in the field. The aim of the current study was to illustrate how
several Mediterranean Orius species could be identified using egg opercula. For
this purpose, the structure of the operculum was described for eggs deposited by
field-collected females, based on scanning electron microscope images. Then,
adult males that developed from these eggs were identified to species by
genitalia examination. A detailed description of diagnostic features of the
operculum is given for each of four Orius species: O. albidipennis (Reuter), O.
niger Wolff, O. laevigatus (Fieber), and O. horvathi (Reuter). Characterizing the
structure of egg opercula of additional Orius species would facilitate ecological
and biological control research in other parts of the world.
PMID- 23156146
TI - Interactive influence of temperature and relative humidity on egg parasitoids of
Riptortus pedestris (Hemiptera: Alydidae).
AB - Previous studies reported that of the two egg parasitoids of Riptortus pedestris
(F.) (Hemiptera: Alydidae) found in Korea, Gryon japonicum (Ashmead)
(Hymenoptera: Scelionidae) appears in soybean fields much earlier than Ooencyrtus
nezarae Ishii (Hymenoptera: Encyrtidae). To explain this phenomenon, we evaluated
the interactive influence of temperature and relative humidity (RH) on the
biological attributes of these parasitoids, including adult parasitoid longevity
and survival. Temperature had significant effects on all the biological
attributes examined for both parasitoids, while RH only affected rates of
parasitism and adult emergence. Interaction between temperature and species, but
not RH and species was found to affect significantly on parasitism. G. japonicum
showed higher relative increment in parasitism than O. nezarae at temperatures
higher than 25 degrees C. No significant differences in progeny sex ratio were
detected for either species at any temperature x humidity combination. RH had no
effect on the developmental time of O. nezarae but on the developmental time of
G. japonicum, which was longer at low RH. Although the biological attributes of
adult parasitoids of both species showed a wide range of adaptability, but it did
not explain the patterns of occurrence of these species in the field. However, G.
japonicum showed greater longevity than O. nezarae at all combinations of
temperature and RH and this may partially explain the seasonal pattern of
occurrence of adult parasitoids in the field previously observed.
PMID- 23156147
TI - Biology of Pseudoligosita plebeia (Hymenoptera: Trichogrammatidae), an egg
parasitoid of Homalodisca spp. (Hemiptera: Cicadellidae) collected from
northwestern Mexico as a potential biocontrol agent of H. Vitripennis in
California.
AB - Pseudoligosita plebeia (Perkins) (Hymenoptera: Trichogrammatidae) is a candidate
biological control agent targeting the glassy-winged sharpshooter, Homalodisca
vitripennis (Germar) (Hemiptera: Cicadellidae), in California. Little is known
about the biology of P. plebeia. Here we report the results of laboratory studies
describing the longevity of P. plebeia adults provided alternative food
resources, their ability to parasitize H. vitripennis eggs of different ages,
lifetime offspring production when provided steady access to excess host eggs,
and levels of mature ovarian eggs present when wasps were held without access to
hosts. P. plebeia is a gregarious parasitoid, with up to six adults emerging from
a single H. vitripennis egg. When provided with honey and water, water alone, or
no food or water, P. plebeia adult females lived an average of 64.1, 2.3, and 2.0
d, respectively. P. plebeia were able to successfully parasitize all ages of H.
vitripennis eggs (1-8 d old), with higher parasitism in younger host eggs (1-3 d
old) than in older host eggs (5-7 d old). An increasing trend in offspring
production was seen for P. plebeia from adult age 2-26 d followed by a decreasing
trend with offspring produced up to age 75 d. P. plebeia females are at least
partially synovigenic, as they contained fewer mature eggs at younger ages (1 and
3 d old) than at older ages (5, 11, 15, and 31 d old). Our results provide
foundational information regarding the biology of P. plebeia useful for its
further evaluation as a potential biological control agent in California.
PMID- 23156148
TI - Controlled atmosphere and temperature treatment system to disinfest fruit moth,
Carposina sasakii (Lepidoptera: Carposinidae) on apples.
AB - Carposina sasakii Matsumura (Lepidoptera: Carposinidae) is a serious pest of
apples and peaches in Korea and Japan. Because of its limited distribution, C.
sasakii has been identified as a quarantine pest in several countries. The
Controlled Atmosphere/Temperature Treatment System (CATTS) was tested as an
alternative to methyl bromide fumigation to control C. sasakii in apples. The
fifth instar was the most tolerant immature stage to a heat treatment of 44
degrees C for 20 min. When the apples infested with different stages of C.
sasakii were treated under CATTS conditions (heating rate of 16 degrees C/h,
chamber temperature of 46 degrees C, final core temperature of 44 degrees C under
1% O2/15% CO2 atmosphere), young larvae (first-fourth instars) did not survive
after 40 min exposure, but the fifth instars required an exposure of at least 60
min to attain 100% mortality. A partial heat shock protein 90 (hsp90) was cloned
and showed inducible expression in response to heat shock at 44 degrees C. CATTS
suppressed transcription of the hsp90 gene. Apples did not show any appreciable
loss of quality in relation to fruit firmness, sweetness, and decay after a 60
min CATTS treatment. These results suggest that CATTS can be applicable to
control C. sasakii in apples.
PMID- 23156149
TI - Integration of insecticidal, phagostimulatory, and visual elements of an attract
and kill system for apple maggot fly (Diptera: Tephritidae).
AB - The apple maggot fly, Rhagoletis pomonella (Walsh), is a key pest of apple in
eastern North America that has been historically controlled with organophosphate
insecticide applications. Here we report on progress toward development of an
effective and maintenance-free attracticidal sphere system for this pest species.
In our studies, we evaluated lethality of spinosad in combination with a feeding
stimulant (sucrose) to replace a Tangletrap sticky coating as the killing agent
of a sphere-based behavioral control system. Spinosad was incorporated into
cylindrical and contoured controlled-release caps that were fixed atop visually
stimulating sphere bases. For both cap styles, spinosad at or near 1.0% (a.i.)
proved to be a relatively durable fly-killing agent, providing approximately
equal to 85% mortality after simulated rainfall exposure reflective of average
season-long precipitation levels experienced during the primary period of risk of
apple maggot injury to fruit in the northeastern United States. In field trials,
we assessed the impact of color degradation of contoured controlled-release caps
on visual responsiveness of apple maggot fly and found that it had no significant
impact on captures. In commercial orchard trials designed to evaluate the
potential of attracticidal spheres with contoured caps for direct control of
apple maggot, a perimeter-based deployment provided protection comparable to
plots receiving 1-2 whole-plot insecticide applications.
PMID- 23156150
TI - Field trials of solid triple lure (trimedlure, methyl eugenol, raspberry ketone,
and DDVP) dispensers for detection and male annihilation of Ceratitis capitata,
Bactrocera dorsalis, and Bactrocera cucurbitae (Diptera: Tephritidae) in Hawaii.
AB - Solid Mallet TMR (trimedlure [TML], methyl eugenol [ME], raspberry ketone [RK])
wafers and Mallet CMR (ceralure, ME, RK, benzyl acetate) wafers impregnated with
DDVP (2,2-dichlorovinyl dimethyl phosphate) insecticide were measured in traps as
potential detection and male annihilation technique (MAT) devices. Comparisons
were made with 1) liquid lure and insecticide formulations, 2) solid cones and
plugs with an insecticidal strip, and 3) solid single and double lure wafers with
DDVP for captures of Mediterranean fruit fly, Ceratitis capitata (Wiedemann);
oriental fruit fly, Bactrocera dorsalis Hendel; and melon fly, B. cucurbitae
Coquillett. Bucket and Jackson traps were tested in a coffee plantation near
Eleele, Kauai Island, HI (trials at high populations) and avocado orchards near
Kona, HI Island, HI (trials at low populations). Captures of all three species
with Mallet TMR were not different from Mallet CMR; therefore, subsequent
experiments did not include Mallet CMR because of higher production costs. In MAT
trials near Eleele, HI captures in AWPM traps with Mallet TMR wafers were equal
to any other solid lure (single or double) except the Mallet ME wafer. In survey
trials near Kona, captures of C. capitata, B. cucurbitae, and B. dorsalis with
Mallet TMR wafers were equal to those for the standard TML, ME, and C-L traps
used in FL and CA. A solid Mallet TMR wafer is safer, more convenient to handle,
and may be used in place of several individual lure and trap systems, potentially
reducing costs of large survey and detection programs in Florida and California,
and MAT programs in Hawaii.
PMID- 23156151
TI - Identification and field bioassay of the sex pheromone of Trichophysetis cretacea
(Lepidoptera: Crambidae).
AB - The jasmine bud borer Trichophysetis cretacea (Butler) (Lepidoptera Crambidae) is
an important agricultural pest of jasmine flowers Jasminum sambac in China. The
extract from the pheromone gland of the female moth was analyzed by gas
chromatography coupled to mass spectroscopy (GC-MS). (Z)-11-hexadecenyl acetate
(Z11-16:Ac), (Z)-11-hexadecenal (Z11-16:Ald),and (Z)-11-hexadecenol (Z11-16:OH)
were identified as the probable sex pheromone components. The electroantennogram
(EAG) bioassay confirmed the results from the chemical analysis. Field bioassays
conducted in the late summer and fall in Quanwei, Sichuan, China, showed that the
synthetic chemical blend of Z11-16:Ac, Z11-16:Ald, and Z11-16:OH was highly
attractive to male T. cretacea moths, and none of the three components was
attractive by itself. All three components were necessary and the ratio of the
three was critical. The highest number of male moths was captured when the ratio
of Z11-16:Ac: Z11-16:Ald:Z11-16:OH was 10:10:1 at a dosage per lure of 200 microg
Z11-16:Ac. The binary mixture of 200 microg Z11-16:Ac and 25 microg Z11-16:OH
captured a number of Nymphicula mesorphna (10.3 +/- 4.4). The results indicate
that traps with synthetic pheromone lures can be used to monitor jasmine bud
borer populations in the field and potentially to control this pest.
PMID- 23156152
TI - Thermal requirements and development of Herpetogramma phaeopteralis (Lepidoptera:
Crambidae: Spilomelinae).
AB - ABSTRACT The tropical sod webworm, Herpetogramma phaeopteralis Guenee is a major
turfgrass pest in the southeastern United States. We evaluated larval development
on five artificial diets and at six temperatures (15, 20, 25, 30, 32.5, 35 +/- 1
degree C) on St. Augustinegrass (Stenotaphrum secundatum (Walter) Kuntze). Only
larvae fed St. Augustinegrass and soy-wheat germ diets completed their
lifecycles. None of the artificial diets tested (corn-based, soy-wheat germ, corn
cob-wheat germ, corn cob-soy flour, or pinto bean) were suitable for rearing this
species, because of high mortality and slower developmental time. Total
developmental time (oviposition to adult) on S. secundatum significantly
decreased from 47.8 d at 20 degrees C to 21.1 d at 30 degrees C, and then
increased to 32.6 d at 32.5 degrees C. Tropical sod webworm failed to complete
larval development at 15 and 35 degrees C. The relationship between temperature
and developmental rate was described using linear (common and polynomial) and
nonlinear models (Briere-1, Briere-2, and Lactin-2). The estimated lower
temperature thresholds using a linear model for eggs, first, second, third,
fourth, fifth, and sixth instars, prepupa, pupa, and total development were 10.1,
6.9, 12.3, 10.5, 15.3, 13.9, 9.1, 13.1, 12.0, and 13.1 degrees C, and the thermal
constant of these stages were 62.9, 66.2, 38.2, 40.3, 24.9, 32.3, 51.9, 106.4,
109.9, and 370.4 degree-days, respectively. The Briere-1 model provided the best
fit with estimated lower, upper, and optimum thresholds for total development of
14.9, 34.3, and 29.4 degrees C, respectively. The developmental requirements of
H. phaeopteralis can be used to help predict the distribution and seasonal
phenology of this pest.
PMID- 23156153
TI - Temperature-dependent demography of Aulacaspis yasumatsui (Hemiptera:
Diaspididae).
AB - Aulacaspis yasumatsui Takagi continues to threaten the extinction of the endemic
and endangered Cycas taitungensis (Shen et al.) in Taiwan. Failure to understand
its population demographic parameters in detail will continue to hinder the
success of pest management practices. An in-depth knowledge of the development,
survival, and fecundity of A. yasumatsui under different environmental conditions
is necessary to understand its' population growth. The demography of A.
yasumatsui was studied in the laboratory based on the age-stage, two-sex life
table at 20, 23, 25, 28, and 31 degrees C, 70% relative humidity, and a
photoperiod of 16:8 (L:D) h. The intrinsic rate of increase (r) under these
temperatures was 0.06, 0.07, 0.09, 0.10, and 0.08 d(-1), respectively. The net
reproductive rate (R0) was 46.27, 47.78, 69.50, 96.08, and 56.65 offsprings per
individual and the mean generation time (T) was 65.60, 55.81, 47.82, 44.15, and
51.42 d, respectively. A. yasumatsui does well at warmer temperatures (25-28
degrees C); however, its performance is disrupted at lower temperatures. This
study provides insight on how to minimize growth and destruction of A. yasumatsui
and conservation of Cy. taitungensis; new cycad reserves should be set up in
cooler areas in Taiwan.
PMID- 23156154
TI - The insecticidal activities of fire ant (Hymenoptera: Formicidae) venoms against
Plutella xylostella (Lepidoptera: Plutellidae) larvae.
AB - Although fire ants frequently have negative impacts on agricultural systems and
public health, they have additional beneficial insecticidal effects. To evaluate
the potential effect of fire ant venoms on agricultural pests, the compositions
of the venoms and their insecticidal activities against Plutella xylostella (L.)
larvae were evaluated under laboratory conditions. The alkaloids found in
Solenopsis geminata (F.) venom are primarily saturated C11, which occur in both
cis and trans forms, whereas the venom of S. invicta Buren contains six principal
alkaloids (from trans C1, to C17). Moreover, the proportions of unsaturated
alkaloids in the venom of polygynous S. invicta were significantly higher than
the corresponding proportions in the monogynous S. invicta, as shown by our
previous studies. Fire ant venoms were topically applied to the dorsal thoracic
region of fourth-instar larvae of P. xylostella. The results of the experiment
showed that the larval symptoms induced by fire ant venom include contractile,
flaccid paralysis, black coloration and death. P. xylostella larvae were most
susceptible to S. geminata venom. The order of the susceptibilities of the larvae
to the venoms was as follows: S. geminata > S. invicta (monogyne form) > S.
invicta (polygyne form), as measured by the corresponding LT50 values at 24 h.
PMID- 23156155
TI - Mexican rice borer (Lepidoptera: Crambidae) injury to corn greater than to
sorghum and sugarcane under field conditions.
AB - The Mexican rice borer, Eoreuma loftini (Dyar) (Lepidoptera: Crambidae), is the
key pest of sugarcane (Saccharum spp.) in Texas; it can attack several grassy
crop and noncrop host plants and has spread into Louisiana. Through small-plot,
commercial field, and pheromone trap experiments, this study demonstrates that
the pest uses corn, Zea mays L., more than sugarcane and sorghum, Sorghum bicolor
(L.) Moench, but when corn is harvested in late summer, injury to nearby
sugarcane strongly increases during the next approximately equal to 2 mo to
harvest. Corn was more infested than sugarcane and sorghum in commercial fields
regardless of whether sampling occurred on field edges or farther into field
interiors. Differences in numbers of infested stalks and in numbers of larval
entry holes between field edges and interiors were not detected. We found that
Mexican rice borer infestation of corn can cause loss of ears, and lodging,
shattering, and complete destruction of maturing stalks. The larger quantities of
adult Mexican rice borers captured in pheromone-based traps placed at corn field
edges compared with sorghum and sugarcane field edges further indicates that corn
is preferred to sugarcane and sorghum. The basis for the pest's attraction to
corn and implications to potential range expansion to other U.S. sugarcane
growing regions are discussed.
PMID- 23156156
TI - Early season host plants of Apolygus lucorum (Heteroptera: Miridae) in northern
China.
AB - Apolygus lucorum (Meyer-Dur) (Heteroptera: Miridae) has become a severe pest of
cotton and many other crops in northern China as a result of the widespread
adoption of Bacillus thuringiensis (Berliner) cotton, with a corresponding
reduction of broad-spectrum insecticide application in cotton fields. From the
middle of April to middle June, A. lucorum feeds and develops on other host
plants before dispersing to cotton fields. Effective suppression of A. lucorum
populations before they enter cotton fields may be an excellent strategy for
reducing the occurrence and damage of their subsequent generations in cotton
fields. For that, basic information about the host plant range of A. lucorum
during the early season is needed. Between 2006 and 2010, a total of 94 plant
species from 41 families covering 39,956 square meters of land in natural
conditions were sampled using the standard white pan beat method. Sixty-six plant
species, including 45 weeds, 10 fruit trees, 5 timber trees, 4 pasture crops, and
2 arable crops were found to be hosts of A. lucorum. Among these species,
Descurainia sophia (L.) Webb ex Prantl, Humulus scandens (Loureiro) Merrill,
Zizyphus jujuba Miller, Vitis vinifera L., Viciafaba L., and Medicago sativa L.
were identified as dominant host species because of their wide distribution and
high population densities of A. lucorum. The results of this study provide useful
information about the early season host range of A. lucorum, which can be used to
develop effective strategies to control the pest before its dispersal to cotton
fields.
PMID- 23156157
TI - Efficacy and value of prophylactic vs. integrated pest management approaches for
management of cereal leaf beetle (Coleoptera: Chrysomelidae) in wheat and
ramifications for adoption by growers.
AB - Cereal leaf beetle, Oulema melanopus L., can be effectively managed in
southeastern U.S. wheat, Triticum aestivum L., with scouting and a single
insecticide treatment, applied at the recommended economic threshold. However,
many growers eschew this approach for a prophylactic treatment, often tank mixed
with a nitrogen application before wheat growth stage 30. The efficacy of a
prophylactic and an integrated pest management (IPM) approach was compared for 2
yr using small plot studies in North Carolina and regional surveys across North
Carolina and Virginia. Economic analyses were performed, comparing the total cost
of management of each approach using the regional survey data. From a cost
perspective, the prophylactic approach was riskier, because when cereal
leafbeetle densities were high, economic loss was also high. However, fields
under the prophylactic approach did not exceed threshold as often as fields using
IPM. Total cost of prophylactic management was also $20.72 less per hectare,
giving this approach an economic advantage over IPM. The majority of fields under
the IPM approach did not exceed the economic threshold. Hence, from an economic
perspective, both the prophylactic and IPM approaches have advantages and
disadvantages. This helps explains the partial, rather than complete, adoption of
IPM by southeastern U.S. wheat growers. Cereal leaf beetle was spatially
aggregated across the region in 2010, but not in 2011. As a result, from an
economic standpoint, prophylaxis or IPM may have a better fit in localized areas
of the region than others. Finally, because IPM adoption is favored when it has a
strong economic advantage over alternative management approaches, more emphasis
should be placed on research to reduce costs within the IPM approach.
PMID- 23156158
TI - Towards integrated pest management in red clover seed production.
AB - The development of integrated pest management is hampered by lack of information
on how insect pest abundances relate to yield losses, and how pests are affected
by control measures. In this study, we develop integrated pest management tactics
for Apion spp. weevils (Coleoptera: Brentidae) in seed production of red clover,
Trifolium pratense L. We tested a method to forecast pest damage, quantified the
relationship between pest abundance and yield, and evaluated chemical and
biological pest control in 29 Swedish red clover fields in 2008 and 2011. Pest
inflorescence abundance, which had a highly negative effect on yield, could be
predicted with pan trap catches of adult pests. In 2008, chemical control with
typically one application of pyrethroids was ineffective both in decreasing pest
abundances and in increasing yields. In 2011, when chemical control included
applications of the neonicotinoid thiacloprid, pest abundances decreased and
yields increased considerably in treated field zones. A post hoc analysis
indicated that using pyrethroids in addition to thiacloprid was largely
redundant. Infestation rates by parasitoids was higher and reached average levels
of around 40% in insecticide treated field zones in 2011, which is a level of
interest for biological pest control. Based on the data presented, an economic
threshold for chemical control is developed, and guidelines are provided on
minimum effective chemical pest control.
PMID- 23156159
TI - Crop residue and residue management effects on Armadillidium vulgare (Isopoda:
Armadillidiidae) populations and soybean stand densities.
AB - In general, Armadillidium vulgare (Latreille) are considered nonpests of soybean
[Glycine max (L.) Merrill], but changes in soil conservation practices have
shifted the pest status of this organism from an opportunistic to a perennial,
early-season pest in parts of central Kansas. As a result, soybean producers that
rotate with corn (Zea mays L.) under conservation tillage practices have resorted
to removing excess corn residue by using controlled burns. In a 2-yr field study
(2009-2010), we demonstrated that residue removal in burned compared with
unburned plots (measured as previous crop residue weights) had minimal impact on
numbers of live and dead A. vulgare, soybean seedling emergence, and isopod
feeding damage over time. Specifically, removal of residue by burning did not
result in higher emergence rates for soybean stands or less feeding damage by A.
vulgare. In a separate study, we found that number of live A. vulgare and residue
weights had no consistent relationship with seedling emergence or feeding damage.
Furthermore, seedling emergence was not impacted by higher numbers ofA. vulgare
in unburned plots, indicating that emergence in this study may have been
influenced by factors other than A. vulgare densities. These studies demonstrate
that removing residue through controlled burning did not impact seedling
emergence in presence of A. vulgare and that residue and feeding damage to
seedlings did not consistently relate to A. vulgare densities. Other factors that
may have influenced a relationship between residue and live isopod numbers, such
as variable moisture levels, are discussed.
PMID- 23156160
TI - Preference of Formosan subterranean termites for blue-stained southern yellow
pine sapwood.
AB - Little research has been conducted to investigate interactions between the
invasive Formosan subterranean termite, Coptotermes formosanus Shiraki, and pine
bark beetles native to the southeastern United States. Facilitative interactions
between these organisms could alter stand dynamics and impact wood utilization
strategies. American Wood Protection Association Standard E1-09 choice tests were
carried out to determine the feeding preference of Formosan subterranean termites
for blue-stained versus unstained southern yellow pine sapwood. Three separate
colonies of Formosan subterranean termites consumed on average twice as much air
dried blue-stained southern yellow pine sapwood over unstained air-dried
controls. Additionally, Formosan subterranean termites consumed over five-times
more kiln-dried blue-stained sapwood than unstained kiln-dried control wafers.
The implications of these results are particularly relevant to pine forest
ecology, nutrient cycling, and the utilization of blue-stained southern pine
building products in the southeastern United States, where Formosan subterranean
termites have become established.
PMID- 23156161
TI - Retail firewood can transport live tree pests.
AB - Untreated firewood can harbor destructive insects and pathogens and transport
them to uninfested areas. In a national survey of retail locations selling
firewood in 18 states, over half (52%) of the firewood was from sources out of
the purchase state and 50% showed evidence of insect infestation. In a three
state survey of southern Rocky Mountain retailers, the most common retailer types
carrying firewood were grocery stores and department or big box stores followed
by gas stations or convenience stores. In 2007-2009, we purchased 419 firewood
bundles from retailers in Colorado, New Mexico, Utah, and Wyoming and caged the
firewood to quantify insect emergence. Live insects emerged from 47% of firewood
bundles over 18 mo of rearing time. Approximately 11 insects emerged on average
from each infested bundle (1-520 per bundle). Pine, fir, and mixed-conifer
bundles yielded the greatest number of insects. Beetles (Coleoptera) were
prominent and made up the majority of individuals (3-60 individuals in each of 24
families). Most Coleoptera were bark and ambrosia beetles (subfamily Scolytinae)
while wood borers (Buprestidae, Cerambycidae, Siricidae) occurred in lower
numbers. Firewood with evidence of previous or current insect infestation was
more likely to have insects emerge than firewood without such evidence. The risk
of moving live native or nonindigenous insects in untreated firewood is high
because insects emerged up to 558 d from purchase date. Retail firewood should be
heat treated in a manner to eliminate insects that is uniformly accepted across
North America.
PMID- 23156162
TI - Spatial dynamics of the invasive defoliator amber-marked birch leafminer across
the Anchorage landscape.
AB - The amber-marked birch leafminer (Profenusa thomsoni [Konow]) (Hymenoptera:
Tenthredinidae) has caused severe infestations of birch species in Anchorage, AK,
since 2002. Its spatial distribution has been monitored since 2006 and summarized
using interpolated surfaces based on simple kriging. Results indicate that this
insect pest is unevenly distributed, occurring in multineighborhood sized patches
that migrate from year to year. Patches showing heavy infestation one year are
followed by light infestations the following year. In this study, we developed
methods of assessing and describing spatial distributions of P. thomsoni as they
vary from year to year, and speculate on potential causes of these trends in
landscape patterns.
PMID- 23156163
TI - Efficacy of "Verbenone Plus" for protecting ponderosa pine trees and stands from
Dendroctonus brevicomis (Coleoptera: Curculionidae) attack in British Columbia
and California.
AB - The western pine beetle, Dendroctonus brevicomis LeConte (Coleoptera:
Curculionidae, Scolytinae), is a major cause of ponderosa pine, Pinus ponderosa
Douglas ex Lawson, mortality in much of western North America. We review several
years of research that led to the identification of Verbenone Plus, a novel four
component semiochemcial blend [acetophenone, (E)-2-hexen-1-ol + (Z)-2-hexen-1-ol,
and (-)-verbenone] that inhibits the response of D. brevicomis to attractant
baited traps, and examine the efficacy of Verbenone Plus for protecting
individual trees and forest stands from D. brevicomis infestations in British
Columbia and California. In all experiments, semiochemicals were stapled around
the bole of treated trees at approximately equal to 2 m in height. (-)-Verbenone
alone had no effect on the density of total attacks and successful attacks by D.
brevicomis on attractant-baited P. ponderosa, but significantly increased the
percentage of pitchouts (unsuccessful D. brevicomis attacks). Verbenone Plus
significantly reduced the density of D. brevicomis total attacks and D.
brevicomis successful attacks on individual trees. A significantly higher
percentage of pitchouts occurred on Verbenone Plus-treated trees. The application
of Verbenone Plus to attractant-baited P. ponderosa significantly reduced levels
of tree mortality. In stand protection studies, Verbenone Plus significantly
reduced the percentage of trees mass attacked by D. brevicomis in one study, but
in a second study no significant treatment effect was observed. Future research
should concentrate on determining optimal release rates and spacings of release
devices in stand protection studies, and expansion of Verbenone Plus into other
systems where verbenone alone has not provided adequate levels of tree
protection.
PMID- 23156164
TI - Seasonal phenology of Ferrisia gilli (Hemiptera: Pseudococcidae) in commercial
pistachios.
AB - The mealybug Ferrisia gilli Gullan is a serious new pest of pistachios in
California. It was first found near the town of Tulare in the late 1990s and has
since spread to orchards in most pistachio-producing regions of the state. The
seasonal phenology of F. gilli was evaluated in a commercial pistachio orchard in
Tulare County during 2005 and 2006. During both seasons E gilli overwintered as
small nymphs and had three complete generations per year. Mealybug population
densities were low and remained as immatures in March and April; by late May
adult females formed and averaged (+/- SE) 1.3 +/- 0.3 and 1.2 +/- 0.3 per 0.75 m
of sample branch in 2005 and 2006, respectively. The first in-season generation
occurred from early June through mid-July, with mealybug densities ranging from
17.6 +/- 5.6-26.4 +/- 6.2 mealybugs per 0.75 m sample branch. The second in
season generation occurred from late July through September and had peak
densities of 408.6 +/- 93.9 and 182.0 +/- 34.2 mealybugs per branch. In March and
April mealybugs were located primarily on the buds and branch wood; in May the
population was on branch wood as well as the rachis; from June through September
the population was located primarily in the pistachio cluster. F. gilli's
seasonal phenology described herein was used to develop a management program.
PMID- 23156165
TI - Rainfastness of insecticides used to control Japanese beetle in blueberries.
AB - Field-based bioassays were used to determine the relative impact of rainfall on
the relative toxicity of four insecticides, phosmet, carbaryl, zeta-cypermethrin,
or imidacloprid, from different chemical classes on adult Japanese beetles,
Popillia japonica Newman, in highbush blueberries, Vaccinium corymbosum L.
Bioassays were set up 24 h after spraying occurred and Japanese beetle condition
was scored as alive, knockdown or immobile 1, 24, and 48 h after bioassay setup.
All insecticides were significantly more toxic than the untreated control and
zeta-cypermethrin consistently had the greatest toxic effect against the Japanese
beetles. All insecticides experienced a decrease in efficacy after simulated
rainfall onto treated blueberry shoots, although the efficacy of zeta
cypermethrin was the least affected by rainfall. This study will help blueberry
growers make informed decisions on when reapplications of insecticides are needed
in the field with the aim of improving integrated pest management (IPM).
PMID- 23156166
TI - Communication disruption of Epiphyas postvittana (Lepidoptera: Tortricidae) by
using two formulations at four point source densities in vineyards.
AB - Light brown apple moth [Epiphyas postvittana (Walker)] is now established as an
economic and quarantine pest in California, and new technologies are being
investigated to increase options for its management. Two new organic formulations
for mating disruption, SPLAT LBAM HD-O and organic Hercon Biotie (biodegradable)
were field tested at four point source densities (25, 72, 322, and 500/ha) and
compared with the standard Isomate LBAM Plus (500/ha, as a positive control) and
an untreated (negative) control. Assessment involved trapping using synthetic
lures and virgin females. In total, 175,776 male light brown apple moths were
caught to both the caged females and synthetic lures, from 10 February to 19 May
2011. The light brown apple moth catch dramatically decreased from baseline
measurements after the treatments were applied, with the highest density
treatments reducing catch to below 10% of the catch in the untreated controls
within the first week (> 90% disruption). In synthetic lure traps, the SPLAT and
Biotie treatment performed similarly well over all rates (P = 0.317 for
posttreatment percentage communication disruption), but SPLAT performed better at
disrupting virgin female traps (P = 0.045). There was a significant increase in
disruption with an increasing number of points/ha (P < 0.001). Disruption of
communication was similar for all three technologies (SPLAT, Biotie and Isomate)
at 500 points/ha for both types of trap (P > 0.74). Disruption of this species in
vineyards is thus highly feasible.
PMID- 23156168
TI - Whole-farm mating disruption to manage Grapholita molesta (Lepidoptera:
Tortricidae) in diversified New Jersey orchards.
AB - Fruit orchards in New Jersey are usually isolated from neighboring farms and
diversified, often containing separate plantings of peach (Prunus spp.) and apple
(Malus spp.). These crops can suffer significant damage from oriental fruit moth,
Grapholita molesta (Busck) (Lepidoptera: Tortricidae). This study evaluated the
effect of managing G. molesta by using sex pheromone-based mating disruption
applied to both peaches and apples (whole-farm mating disruption) rather than
treating either crop alone. In year 1 of the experiment, G. molesta mating
disruption applied to the adjacent peach and apple blocks provided better control
than treating peaches or apples alone. During year 2, treating these adjacent
blocks or only treating apples controlled G. molesta equally well. G. molesta
populations were so low at the end of year 2 that mating disruption was not
applied against this pest during year 3. This allowed us to determine whether
applying mating disruption for two consecutive years controlled G. molesta well
enough that it eliminated the need mating disruption for three consecutive years.
The mean cumulative number of G. molesta captured in plots where both peaches and
apples had been treated did not exceed two moths per trap in the third year of
this experiment. In contrast, G. molesta capture rebounded during August in
peaches and apples that had not been treated with mating disruption the previous
2 yr. Implications for managing G. molesta by using mating disruption as a "whole
farm" tactic as well applying it for two consecutive years and not a third year
are discussed.
PMID- 23156167
TI - Field efficacy and application timing of methoxyfenozide, a reduced-risk
treatment for control of navel orangeworm (Lepidoptera: Pyralidae) in almond.
AB - Large-scale field efficacy trials of methoxyfenozide (Intrepid), a reduced-risk
molting agonist insecticide, were conducted in 2004 and 2005 in an orchard
containing 'Nonpareil' and 'Sonora almonds [Prunus dulcis (Mill.) D.A. Webb]
located in Kern County, CA. Methoxyfenozide applied one to three times, the
organophosphate phosmet (Imidan) alone or in combination with methoxyfenozide, or
the pyrethroid permethrin (Perm-Up) were tested for efficacy against the primary
lepidopteran pest navel orangeworm, Amyelois transitella (Walker) (Lepidoptera:
Pyralidae), and three other lepidopteran pests of almond: oriental fruit moth,
Grapholita molesta (Busck); oblique-banded leafroller, Choristoneura rosaceana
(Harris); and peach twig borer, Anarsia lineatella Zeller. Two or three
applications of methoxyfenozide (bracketing hull split or spring plus bracketing
hull split) were more effective than a single hull split application of phosmet,
phosmet combined with permethrin, or methoxyfenozide. In these trials, a spring
application followed by a posthull split application was as effective as the
applications bracketing hull split. Navel orangeworm accounted for > 60% of the
total damage, whereas oriental fruit moth and peach twig borer were the dominant
secondary pests. In experiments conducted in 2010 to assess the direct toxicity
of methoxyfenozide to navel orangeworm eggs under field conditions, exposure to
methoxyfenozide reduced survival by 96-99%. We conclude that this reduced-risk
insecticide is effective, although its efficacy is maximized with more than one
well-timed application.
PMID- 23156169
TI - Evaluation of the predation capacity of Podisus maculiventris (Hemiptera:
Pentatomidae) on Microtheca ochroloma (Coleoptera: Chrysomelidae) in field cages.
AB - The predation capacity of the spined soldier bug, Podisus maculiventris (Say)
(Hemiptera: Pentatomidae), was evaluated at three release rates in field cages
containing larvae of the yellowmargined leaf beetle, Microtheca ochroloma Stal
(Coleoptera Chrysomelidae), a pest of organic crucifer (Brassicaceae) crops in
the United States. The experiment was conducted twice, in February-March 2009 and
in February-March 2010. On the same day as the introduction of 132 first instars
of M. ochroloma into the cages, four (= low), 10 (= medium), or 16 (= high) first
instars of P. maculiventris were released evenly among six turnip (Brassica rapa
L.) plants in cages. Control treatment cages received no predators. In 2009, the
mean number of M. ochroloma larvae declined progressively during the first four
sampling dates. On the final (seventh) sampling date, the mean numbers of total
M. ochroloma in the two higher release-rate treatments were significantly lower
than in the low release-rate and control treatments. Overall survivorship of P.
maculiventris was 39.1% in the high release-rate treatment. In 2010, the mean
number of M ochroloma larvae declined progressively during the first four
sampling dates. On the fourth sampling date and the final (ninth) sampling date,
there were no significant differences among treatments involving predator
releases. The lowest overall survivorship of P. maculiventris (3.1%) was in the
high release-rate treatment. Two tentative recommendations for growers emerged
from this study: 1) release 10 first instars of P. maculiventris per six plants
if the plants are expected to have > or = 7 leaves per plant; or 2) release four
first instars of P. maculiventris per six plants if the plants are expected to
have < or = 6 leaves per plant.
PMID- 23156170
TI - Impact of insecticides on the invasive Halyomorpha halys (Hemiptera:
Pentatomidae): analysis of insecticide lethality.
AB - The efficacy of 37 insecticide treatments against adult Halyomorpha halys (Stal)
was established based on exposure to 18-h old dry insecticide residue in
laboratory bioassays. Individual adult H. halys were exposed to an insecticide
residue for 4.5 h and then monitored daily for survivorship over a 7-d period.
The proportion of dead and moribund insects was used as an estimate of overall
insecticide efficacy against H. halys immediately after the exposure period and
over the 7-d trial. Among all materials evaluated, 14 insecticides exhibited
increasing efficacy, in which the percentage of dead and moribund insects (used
as a measure of insecticide efficacy) increased by > 10% after 7 d. By contrast,
insecticide efficacy values of eight insecticides declined by > 10% (based on
recovery of adults from a moribund state) over the 7-d period with most belonging
to the pyrethroid class. In this study, the efficacy value of neonicotinoid,
acetamiprid, showed the greatest decline from 93 to 10% over 7 d. A lethality
index (scale of 0-100) was developed to compare insecticides based on quantifying
the immediate and longer-term effects of insecticide exposure on H. halys. Among
all materials evaluated, dimethoate, malathion, bifenthrin, methidathion,
endosulfan, methomyl, chlorpyrifos, acephate, fenpropathrin, and permethrin
yielded the highest values (> 75) because of a high degree of immediate mortality
with very little recovery. Our results provide baseline information regarding
potential of candidate insecticides against adult H. halys and highlight the need
to consider longer-term effects in establishing overall efficacy ratings against
this invasive species.
PMID- 23156171
TI - Toxicity and horizontal transfer of chlorantraniliprole in the eastern
subterranean termite.
AB - Toxicity and horizontal transmission of chlorantraniliprole were measured against
field-collected eastern subterranean termites, Reticulitermes flavipes (Kollar).
Chlorantraniliprole was highly toxic to termite workers in brief and continuous
exposure assays across arange of concentrations from 5 to 100 ppm. All doses
tested resulted in 100% mortality in the termites in 14 d. The effect of exposure
route (topical, oral, or both) was investigated by exposing termites to treated
substrate only, treated food only, or both. Results indicate that exposure route
has no significant effect on chlorantraniliprole toxicity and demonstrate that
chlorantraniliprole is highly active by feeding and contact. Results of feeding
assays (paper consumption tests) demonstrate that as little as 5-ppm
chlorantraniliprole applied to sand prevents termites from consuming cellulose
that is in contact with the treated sand. Termites on untreated soil consumed 79
+/- 3% of the available paper in 3 d, whereas termites on chlorantraniliprole
treated did not consume any paper before they became symptomatic and died.
Results of transfer tests demonstrate that chlorantraniliprole is transferred
efficiently among the termites. The rate and the level of secondary mortality in
the recipient termites depend on both the concentration of chlorantraniliprole
and the duration of exposure in the donors. Little secondary mortality was
observed with the lowest dose of 5 ppm, which was effective at killing the donor
termites, but insufficient to cause mortality in the recipient termites. In
contrast, highly efficient transfer was observed with 25 and 50 ppm
chlorantraniliprole. Both doses resulted in 100% mortality in the donors and the
recipients at 21 d after exposing the recipients to the treated donors. These
data demonstrate that chlorantraniliprole has dose-independent toxicity, delayed
toxicity, and is readily transferred in eastern subterranean termites.
PMID- 23156172
TI - Potential of natural products and their derivatives to control Formosan
subterranean termites (Isoptera: Rhinotermitidae).
AB - Twenty-nine natural products and their derivatives were tested for both contact
and vapor toxicity against the Formosan subterranean termite, Coptotermes
formosanus Shiraki (Isoptera: Rhinotermitidae). Five natural products at 0.5%
(wt:wt) in petri dish contact assay caused 100% mortality within 3 d. In vapor
form, only three chemicals (styrallyl alcohol, 2-phenyl-2-propanol, and l
carvone) at 0.25 microl/liter air caused > 90% mortality in 3 d when tested on
exposed termites: However, when termites were shielded by wood and soil, only one
chemical, tetrahydrocarvone at 25 microl/liter air caused 100% mortality in 2 d.
Preliminary test with termites in carton nests, exposed to tetrahydrocarvone
vapor in desiccators, resulted in an average of 98.6% mortality in 7 d. With
further development in the method of delivery, this chemical may be very useful
in fumigating confined areas of termite infestation.
PMID- 23156173
TI - Effect of scattered and discrete hydramethylnon bait placement on the Asian
needle ant.
AB - The Asian needle ant (Pachycondyla chinensis Emery) is invading natural and
disturbed habitats across the eastern United States. While recent studies
document the impact of P. chinensis on native ecosystems and human health,
effective control measures remain unknown. Thus, we evaluated the field
performance of a hydramethylnon granular bait, Maxforce Complete Granular Insect
Bait, dispersed in clumps or scattered against P. chinensis. We also measured the
effect of this bait on P. chinensis outside of the treatment zone. Surprisingly,
unlike reports for other ant species, we achieved nearly complete P. chinensis
population reductions 1 d after treatments were applied. Significant ant
reductions were achieved until the end of our study at 28 d. No difference was
recorded between clumped and scattered application methods. We found no overall
difference in ant reductions from the edge out to 5 m beyond the treatment zone.
Other local ant species appeared to be unaffected by the bait and foraging
activity increased slightly after P. chinensis removal from treated areas. We
suggest that Maxforce Complete Granular Insect Bait can be effective in an Asian
needle ant treatment program.
PMID- 23156174
TI - Evaluation of three bait materials and their food transfer efficiency in Formosan
subterranean termites (Isoptera: Rhinotermitidae).
AB - The consumption and food transfer efficiency of two commercially used termite
bait materials, southern yellow pine wood and cardboard, and one potential bait
material, maize (Zea mays L.) cob, were evaluated for use against the Formosan
subterranean termite, Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae),
in the laboratory. In the no-choice test, the consumption of wood and cob was
similar and significantly more than cardboard. Tunneling under the food sources
was similar. In the two-choice test, the consumption was cob > wood, wood >
cardboard, cob = cardboard, and tunneling under these choices was cob = wood,
wood = cardboard, cob > cardboard. In the three-choice test, no significant
difference was detected in consumption, but tunnels made under the cob were
significantly more than wood and cardboard. Nile blue A was used to study food
transfer of bait material among termite cohorts. Dyed cardboard, cob, or wood
(0.1% Nile blue A) was provided to termites as food. Termites feeding on wood
turned blue in significantly greater number at 6 h compared with cardboard and
cob, but there was no significant difference after 12 h. Blue termites feeding on
different bait materials were then collected and combined with undyed termites.
When undyed (white) termites were placed with blue termites and food (wood
block), termites turned blue in the same percentage regardless of original bait
material fed on. However, when no food was provided (starvation group), the rate
of white termites turning blue was dramatic; in dyed wood treatment,
significantly more termites turned blue than that of cardboard, although neither
were significantly different from cob. Our study is the first to show that, cob,
an otherwise waste product of the food and biofuel industry, is as efficient as
wood and cardboard as a termite bait matrix.
PMID- 23156175
TI - Toxicity and horizontal transfer of 0.5% fipronil dust against Formosan
subterranean termites.
AB - The toxicity and horizontal transfer of a new formulation of fipronil, 0.5%
fipronil dust, was tested against Coptotermes formosanus Shiraki in the
laboratory. The formulation was applied in three different ways: 1) Directly
applied to termites (donors) and mixed with untreated termites (recipients) at
three ratios, viz., 50 donors: 50 recipients, 20 donors: 80 recipients and 10
donors: 90 recipients. 2) Applied onto the surface of 3 mm thick sand or soil
substrate in a petri dish and then topped with another 3 mm thick sand or soil
layer whereupon termites were released. 3) Applied to the inner surface of a tube
(either 5 cm or 15 cm long) that connected two foraging dishes, one containing
dry sand and the other moist sand plus a wood block and termites were released
into the dry sand dish. All donors and >93% of the recipients were dead by 42 h
after treatment in the direct treatment experiment. Significant mortalities of
both donors and recipients were observed at 5 h after treatment at all donor:
recipient ratios. During this period, the mortality of the recipients (but not
donors) at 10:90 was significantly lower than those at the other two ratios. All
termites were dead at 65 h after exposure (HAE) on the sand treatment and at 190
HAE on soil treatment. More than 96% mortality was observed at 40 HAE on the sand
treatment as compared with only 6% mortality onsoil treatment during the same
time period. In the tube treatment experiment, > 97% mortality was observed at 90
h after release for both tube lengths as compared with < 3% mortality in
controls. About half of the termites were dead by 15 h after release regardless
of the tube length. Our results showed that 0.5% fipronil dust is nonrepellent
and readily transferred from treated to nontreated termites.
PMID- 23156176
TI - Bt pollen dispersal and Bt kernel mosaics: integrity of non-Bt refugia for
lepidopteran resistance management in maize.
AB - Field trials were conducted at Rosemount, MN in 2009 and 2010, to measure pollen
movement from Bt corn to adjacent blocks of non-Bt refuge corn. As the use of Bt
corn hybrids continues to increase in the United States, and new insect
resistance management (IRM) plans are implemented, it is necessary to measure the
efficacy of these IRM plans. In Minnesota, the primary lepidopteran pests of corn
include the European corn borer, Ostrinia nubilalis (Hubner) and corn earworm,
Helicoverpa zea (Boddie). The primary IRM plan in transgenic corn is the use of
hybrids expressing a high dose of insecticidal proteins and an insect refuge
containing hybrids not expressing insecticidal proteins that produce susceptible
insects. Wind-assisted pollen movement in corn occurs readily, and is the primary
method of pollination for corn. The combination of pollen movement and viability
determines the potential for cross pollination of refuge corn. In 2009 and 2010,
cross pollination occurred with the highest frequency on the north and east sides
of Bt corn fields, but was found at some level in all directions. Highest levels
of cross pollination (75%) were found within the first four rows (3 m) of non-Bt
corn adjacent to Bt corn, and in general decreasing levels of cross pollination
were found the further the non-Bt corn was planted from the Bt corn. A mosaic of
Bt cross-pollinated kernels was found throughout the ear, but in both years the
ear tip had the highest percentage of cross-pollinated kernels; this pattern may
be linked to the synchrony of pollen shed and silking between Bt and non-Bt corn
hybrids. The dominant wind direction in both years was from WNW. However, in both
years, there were also prevailing winds from SSW and WSW. Further studies are
needed to quantify Bt levels in cross-pollinated kernels, measure the Bt dose of
such kernels and associated lepidopteran pest survival, and measure the impact of
Bt pollen on lepidopteran pests, particularly when considering the seed mixture
refuge configuration.
PMID- 23156177
TI - Concentration-dependent effects of GABA on insensitivity to fipronil in the A2'S
mutant RDL GABA receptor from fipronil-resistant Oulema oryzae (Coleoptera:
Chrysomelidae).
AB - The beetle Oulema oryzae Kuwayama (Coleoptera: Chrysomelidae), an important pest
of rice, has developed fipronil resistance in Japan. Molecular cloning and
sequence analysis of O. oryzae RDL gamma-aminobutyric acid (GABA) receptor
subunit (OO-RDL) genes from fipronil-susceptible and -resistant O. oryzae
identified the A2'S mutation (index number for the M2 membrane-spanning region).
To investigate the effect of the A2'S mutation on fipronil resistance, we stably
expressed the wild-type and mutant OO-RDL homomers in Drosophila Mel-2 cells. A
membrane potential assay exhibited that the IC50 values of fipronil for
inhibition of the response to EC80 GABA of the wild-type and A2'S mutant OO-RDL
homomers were 0.09 microM and 0.11 microM, respectively. However, the IC50 values
of fipronil for inhibition of the response to EC95 GABA of the wild-type and A2'S
mutant OO-RDL homomers were 0.11 microM and approximately equal to 5 microM,
respectively. These results suggest that the GABA concentration is an important
factor affecting fipronil resistance in O. oryzae carrying the A2'S mutation in
OO-RDL.
PMID- 23156178
TI - Susceptibility of Cimex lectularius (Hemiptera: Cimicidae) to pyrethroid
insecticides and to insecticidal dusts with or without pyrethroid insecticides.
AB - Relative increases of bed bug, Cimex lectularius L., populations are probably due
in large measure to their resistance to pyrethroids, which have been used
extensively against urban pests. A Connecticut population of bed bugs was
assessed for sensitivity to pyrethroids and exposed to commonly-used commercial
insecticides applied to various substrates on which the residues were allowed to
age for 0-24 wk. Type I and type II pyrethroids differed in toxicity when applied
at a high dosage (1 microg) per bed bug. Some type II pyrethroids (cyfluthrin,
lambda-cyhalothrin, cis-cypermethrin, and deltamethrin) caused > 80% mortality,
whereas exposure to type I pyrethroids caused < 5% mortality over 72 h (with one
exception, pyrethrins caused 23% mortality). Dust products were not affected by
residue aging; mortality response over time of exposure closely fit (R2 > 0.95)
an exponential rise to a maximum model from which the survival half-life (S1/2)
was calculated directly. Tempo Dust (Bayer Environmental Science, Montvale, NJ)
killed bed bugs relatively quickly, as did Syloid 244 (Grace Davison, Columbia,
MD) and Drione (Bayer Environmental Science, Montvale, NJ) on hardboard and
mattress fabric substrates (S1/2 < 1 d); DeltaDust (Bayer Environmental Science,
Montvale, NJ) provided a relatively slow kill (S1/2 approximately equal to 3.5
d). The sprayable pyrethroids, Cyonara 9.7 (Insecticide Control solutions,
Pasadena, TX) and D-Force HPX Aerosol 0.06% (Waterbury Companies, Waterbury, CT),
displayed reduced residual toxicity as they aged; the mortality was < 50% on some
substrates after 4 d. Desiccant dusts, with their physical mode of action and
long residual activity, appear to be superior to sprayable pyrethroid products
for killing bed bugs.
PMID- 23156179
TI - Potential efficacy of olyset mosquito netting against Calliphora nigribarbis
(Diptera: Calliphoridae) invasion into livestock barns.
AB - Calliphora nigribarbis Vollenhoven is a possible mechanical transmitter of highly
pathogenic avian influenza. Based on laboratory tests, we evaluated the efficacy
of a long-lasting permethrin-treated mosquito netting, known as the Olyset net,
for the prevention of this species entering livestock barns. Flies were trapped
in Olyset net cages, and two statistics for knockdown and lethal efficacies were
obtained. Median knockdown time in the cage (KT50) was estimated to be 341 s for
females, and median lethal time after exposure to the mesh (LT50) was estimated
to be 30 s and <15 s for females and males, respectively. These LT50s were faster
than those measured for anesthetized stationary flies brought in contact with the
Olyset net (> 120 s for both sexes),indicating that a fly's spontaneous contact
with the Olyset net accelerates insecticide adhesion. The rate of permethrin
adhesion to C. nigribarbis after its spontaneous contact with the Olyset net was
estimated to be 3.7 ng/s for females, in reference to the 50% lethal dose (LD50)
value (112 ng/female), which was obtained from the topical application bioassay
of permethrin. The lethality exhibited after brief spontaneous contact with the
Olyset net suggests its potential utility in poultry farms against C. nigribarbis
invasion.
PMID- 23156180
TI - Genetic characterization of North American populations of the wheat curl mite and
dry bulb mite.
AB - The wheat curl mite, Aceria tosichella Keifer, transmits at least three harmful
viruses, wheat streak mosaic virus (WSMV), high plains virus (HPV), and Triticum
mosaic virus (TriMV) to wheat (Triticum aestivum L.) throughout the Great Plains.
This virus complex is considered to be the most serious disease of winter wheat
in the western Great Plains. One component of managing this disease has been
developing mite resistance in wheat; however, identification of mite biotypes has
complicated deployment and stability of resistance. This biotypic variability in
mites and differential virus transmission by different mite populations
underscores the need to better understand mite identity. However, A. tosichella
has a history of serious taxonomic confusion, especially as it relates to A.
tulipae Keifer, the dry bulb mite. Molecular techniques were used to genetically
characterize multiple A. tosichella populations and compare them to populations
of A. tulipae. DNA from these populations was polymerase chain reaction amplified
and the ribosomal ITS2 region sequenced and compared. These results indicated
limited variability between these two species, but two distinct types within A.
tosichella were found that corresponded to previous work with Australian mite
populations. Further work using sequencing of several mitochondrial DNA genes
also demonstrated two distinct types of A. tosichella populations. Furthermore,
the separation between these two A. tosichella types is comparable to their
separation with A. tulipae, suggesting that species scale differences exist
between these two types ofA. tosichella. These genetic differences correspond to
important biological differences between the types (e.g., biotypic and virus
transmission differences). In light of these differences, it is important that
future studies on biological response differences account for these mite
differences.
PMID- 23156181
TI - Comparative life history and fecundity of Phthorimaea operculella (Lepidoptera:
Gelechiidae) on leaves and tubers of different potato cultivars.
AB - The potato tuberworm, Phthorimaea operculella (Zeller) (Lepidoptera:
Gelechiidae), is a noxious pest of the potato crop (Solanum tuberosum L.) in both
field and storage in tropical and subtropical regions. Survival, development and
reproduction of the potato tuberworm was compared on leaves and tubers of 10
common cultivated potato cultivars including Agria, Agata, Almera, Arinda,
Baneba, Fiana, Marfona, Ramus, Satina, and Volvox at 25 +/- 1 degree C, 65 +/- 5%
RH and a photoperiod of 14:10 (L:D) h. The results indicated that there were
significant differences in the larval, pupal, and total developmental periods on
the various potato cultivars. The total developmental periods varied from 26.6
(on Baneba) to 29.5 d (on Marfona),and ranged from 27.9 (on Marfona) to 30.5 d
(on Agria) in the experiments on potato leaves and tubers, respectively. Immature
survival rates were lowest on Agria (44.1%) and Marfona (40.6%) on potato leaves
and tubers, respectively. The highest total fecundity was observed on Arinda
(78.3 eggs) and Ramus (154.8 egg) on potato leaves and tubers, respectively.
Significantly fewer eggs were laid on Marfona cultivar's leaves (44.6 eggs) and
tubers (72.9 eggs) than any of the other tested potato cultivars. The female
reproduction potential on potato leaves was significantly lower than on potato
tubers. Cluster analysis of the biological parameters of P. operculella on
different potato cultivars demonstrated that Marfona is partially resistant to
potato tuberworm. The findings on the susceptibility or resistance of potato
cultivars could be a fundamental component of integrated pest management programs
for potato tuberworm.
PMID- 23156182
TI - Variation in genetics and performance of Dutch western flower thrips populations.
AB - Invasion of pests may result in local adaptation and the development of biotypes
specialized in different hosts. In this study, we investigated western flower
thrips, Frankliniella occidentalis (Pergande), an invasive pest in Europe. Thrips
from different commercial glasshouse crops within the Dutch Westland and a lab
culture kept on chrysanthemum were compared. Genetic barcoding was applied for
the identification of potential western flower thrips cryptic species in the
Netherlands revealing that all western flower thrips populations studied belonged
to the "glasshouse" strain reported in California as the only existing species in
the Netherlands. Feeding and reproduction parameters in leaf disc and whole plant
bioassays were scored. We detected significant differences in thrips feeding
among host plants and thrips origin. Host plants differed in average thrips
damage while thrips from different origins caused similar amounts of damage
across host plants. In contrast, reproductive success of thrips on all plant
species depended strongly on thrips origin. The thrips lab culture maintained on
chrysanthemum obtained the highest levels of reproduction on chrysanthemum.
Differences among the other thrips populations were relatively small. Amplified
fragment length polymorphisms analyses were used to study genetic differences
between western flower thrips populations and confirmed that the lab culture
population was also genetically the most different of all studied populations.
The results of the amplified fragment length polymorphisms analyses together with
the better reproductive performance of thrips on the host plant on which they
were maintained demonstrate the evolution of a lab biotype specialized in a
particular host. This finding has potential relevance for future crop control and
breeding programs.
PMID- 23156184
TI - Measuring the benefit of biological control for single gene and pyramided host
plant resistance for Aphis glycines (Hemiptera: Aphididae) management.
AB - The soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), is an
economically important pest in the north central United States. In the state of
Iowa, economically damaging populations occurred in seven of 11 growing seasons
from 2001 to 2011. The high frequency and economic impact of the soybean aphid
makes it an ideal candidate for management by using host plant resistance. We
compared an aphid-susceptible line to near-isolines that contain Rag1 and Rag2,
both alone and pyramided together, to suppress aphid populations and protect
yield. Each of four near-isolines, were artificially infested with aphids and
grown in small plots in which the exposure to natural enemies was controlled by
the use of cages, resulting in the following treatment groups: natural enemy free
(only aphids), biocontrol (both aphids and natural enemies), and aphid free (no
aphids or natural enemies). The seasonal accumulation of aphids and the
population growth rates were measured for each line and an estimate of yield was
measured at the end of the season. Soybean aphid population growth rate was
reduced 20% by natural enemies alone, 44% by pyramided resistance, and 63% by the
combination of natural enemies and pyramided resistance. This reduction in
population growth rate resulted in a 99.3% reduction in the pyramid line's
seasonal exposure to aphids. In the presence of natural enemies, all three
resistant lines maintained aphid populations below the economic injury level and
prevented yield loss. This study demonstrates the compatibility of biological
control with soybean aphid host plant resistance and its utility, especially for
single resistance gene lines.
PMID- 23156185
TI - Variation in resistance mechanisms to the green peach aphid among different
Prunus persica commercial cultivars.
AB - ABSTRACT Peaches and nectarines are frequently attacked by the green peach aphid
Myzus persicae (Sulzer), with significant negative impacts on fruit production.
The genetic variability of resistance to this aphid among commercial cultivars of
Prunus persica (L.) Batsch and Prunus persica variety nectarina was evaluated in
this study. In total, 16 cultivars of P. persica were selected to evaluate the
occurrence and population growth rate of M. persicae in commercial orchards, as
well as in no-choice and probing behavior laboratory assays. The results showed
variability between cultivars in resistance and susceptibility to M. persicae,
with three cultivars exhibiting different signatures of resistance. The peach
cultivar 'Elegant Lady' exhibited a low occurrence of aphids in the orchard, a
low rate of growth, moderate leaf-rejection in a no-choice test and a higher
number and longer period of salivation into sieve elements, suggesting resistance
at the phloematic level. The nectarine cultivar 'August Red' also exhibited low
aphid occurrence in the orchard, a low rate of growth, and resistance at the
prephloem and phloem levels. Finally, the nectarine 'July Red-NS92' exhibited a
low occurrence of aphids in the orchard, a higher number of rejections in no
choice assays and no ingestion of phloem during the probing behavior experiments,
suggesting prephloematic resistance. The rest of the cultivars studied exhibited
clear susceptibility. Hence, different resistance mechanisms are apparent among
the studied cultivars. The information gathered in this study regarding the
resistance to M. persicae may assist breeding programs aimed at increasing aphid
resistance to peaches and nectarines.
PMID- 23156183
TI - Evaluation of corn hybrids expressing Cry1F, cry1A.105, Cry2Ab2,
Cry34Ab1/Cry35Ab1, and Cry3Bb1 against southern United States insect pests.
AB - Studies were conducted across the southern United States to characterize the
efficacy of multiple Bacillus thuringiensis (Bt) events in a field corn, Zea mays
L., hybrid for control of common lepidopteran and coleopteran pests. Cry1F
protein in event TC1507 and Cry1A.105 + Cry2Ab2 proteins in event MON 89034 were
evaluated against pests infesting corn on above-ground plant tissue including
foliage, stalks, and ears. Cry34Ab1/Cry35Ab1 proteins in event DAS-59122-7 and
Cry3Bb1 in event MON 88017 were evaluated against the larvae of Mexican corn
rootworm, Diabrotica virgifera zeae Krysan and Smith, which occur below-ground.
Field corn hybrids containing Cry1F, Cry1A.105 + Cry2Ab2, Cry34Ab1/Cry35Ab1, and
Cry3Bb1 insecticidal proteins (SmartStax) consistently demonstrated reductions in
plant injury and/or reduced larval survivorship as compared with a non-Bt field
corn hybrid. Efficacy provided by a field corn hybrid with multiple Bt proteins
was statistically equal to or significantly better than corn hybrids containing a
single event active against target pests. Single event field corn hybrids
provided very high levels of control of southwestern corn borer, Diatraea
grandiosella (Dyar), lesser cornstalk borer, Elasmopalpus lignosellus (Zeller),
and fall armyworm, Spodoptera frugiperda (J.E. Smith), and were not significantly
different than field corn hybrids with multiple events. Significant increases in
efficacy were observed for a field corn hybrid with multiple Bt events for
sugarcane borer, Diatraea saccharalis (F.), beet armyworm, Spodoptera exigua
(Hubner), corn earworm, Helicoverpa zea (Boddie), and Mexican corn rootworm.
Utilization of field corn hybrids containing multiple Bt events provides a means
for managing insect resistance to Bt proteins and reduces non-Bt corn refuge
requirements.
PMID- 23156186
TI - Bayesian estimation for the effectiveness of pesticides and repellents.
AB - In the quantitative estimation of the effectiveness of pesticides and repellents,
Abbott's correction and similar methods have been used for nearly a century.
However, the formulas for such corrections have some disadvantages in performing
range estimations and being used in batched experiments. These disadvantages also
exist in the estimation of EC50, the chemical concentration that produces 50%
mortality. In this study, I propose as a solution to these problems a Bayesian
estimation with a logistic model. This method enables the flexible modeling of
non-normal variables in complex experimental design, for example, life-death
response in a batched experiment. Furthermore, if any knowledge about focal
phenomena exists, it can be used in analyses as a prior distribution, thus
enhancing the accuracy of the estimation.
PMID- 23156188
TI - Gender, sex, and health research: developments and challenges.
PMID- 23156187
TI - Mortality of adult Stomoxys calcitrans fed isolates of Bacillus thuringiensis.
AB - We examined the ability of five isolates of Bacillus thuringiensis Berliner to
cause mortality in adult stable flies, Stomoxys calcitrans (L.). Isolates
Bacillus thuringiensis tolworthi 4L3 (serotype 9), Bacillus thuringiensis
darmstadiensis 4M1 (serotype 10a10b), Bacillus thuringiensis thompsoni 401
(serotype 12), Bacillus thuringiensis thuringiensis HD2 (serotype 1), and
Bacillus thuringiensis kurstaki HD945 (serotype 3a3b3c) were administered to
adult flies in diets containing blood only, sugar only, and both sugar and blood
combined. B. t. tolworthi 4L3 had no effect on adult mortality regardless of the
feeding substrate. The remaining isolates tended to cause the greatest mortality
when administered in blood alone. B. t. thompsoni 401 was the only isolate that
consistently caused adult mortality when fed in blood at concentrations ranging
from 0.21 to 50.0 microg of protein per ml of blood. This isolate also caused
mortality when applied topically. The time to 50% mortality declined with dose
and reached a lower asymptote at approximately equal to 1.3 d at an oral dose of
8.75 microg/ml and at a topical dose of 0.14 microg per fly.
PMID- 23156189
TI - The gendered ovary: whole body effects of oophorectomy.
AB - Since oophorectomy in healthy women predates the commercialization of BRCA
mutations screens, genomics cannot explain entirely why physicians and cancer
specialists recommend this procedure for women at risk. Rather, one must situate
the development of reproductive cancer genomics within a broader sociocultural
context in which researchers bring to bear habits of mind about women,
reproduction and motherhood. (Happe, 2006, p. 173)
PMID- 23156190
TI - An integrative review of nurse attitudes towards lesbian, gay, bisexual, and
transgender patients.
AB - A growing body of literature suggests that lesbian, gay, bisexual, and
transgender (LGBT) persons have significant health disparities as compared to
heterosexuals. Although the reasons for this are complex and multifactorial, one
area of research has examined the real or perceived negative attitudes of health
care providers. This integrative review critically appraises and synthesizes data
from 17 articles regarding nurses' attitudes towards LGBT patients. Every study
analyzed showed some evidence of negative attitudes. However, the literature
revealed major limitations, including a paucity of well-designed studies; a
dearth of qualitative studies; inconsistent use of validated, reliable
instruments; and a lack of measures examining attitudes towards lesbian,
bisexual, and transgender persons. Increased knowledge in this area could lead to
interventions to improve nurses' cultural competency; resource allocation to
nursing research, education, and services related to LGBT health; and inclusion
of more LGBT content in nursing curricula.
PMID- 23156191
TI - Nurses' work with LGBTQ patients: "they're just like everybody else, so what's
the difference"?
AB - Informed by critical feminist and queer studies approaches, this article explores
nurses' perceptions of practice with patients who identify as lesbian, gay,
bisexual, transgender, or queer (LGBTQ). Qualitative in-depth, semi-structured
interviews with 12 nurses in Halifax, Nova Scotia, illuminate a range of
approaches to practice. Most commonly, participants argued that differences such
as sexual orientation and gender identity do not matter: Everyone should be
treated as a unique individual. Participants seemed anxious to avoid
discriminating or stereotyping by avoiding making any assumptions. They were
concerned not to offend patients through their language or actions. When social
difference was taken into account, the focus was often restricted to sexual
health, though some participants showed complex understandings of oppression and
marginalization. Distinguishing between generalizations and stereotypes may
assist nurses in their efforts to recognize social differences without harming
LGBTQ patients.
PMID- 23156192
TI - Supporting fathers' efforts to be smoke-free: program principles.
AB - There is limited empirical evidence on effective ways to develop, distribute, and
evaluate men-centred, gender-sensitive health promotion programs. The purpose of
this research was to transition qualitative findings on men's smoking into father
centred cessation interventions. Men's perspectives were gathered in 4 group
sessions with 24 new fathers who smoked. The data led to the identification of 3
principles for men's health promotion programs: use positive messaging to promote
change without amplifying stigma, guilt, shame, and blame; foster connections
between masculine ideals (e.g., strength, decisiveness, resilience, autonomy) and
being smoke-free; and privilege the testimonials of potential end-users (e.g.,
fathers who smoke and want to quit). Experiences drawn from the design and pilot
testing of a booklet and a group program based on these principles are described.
The findings can be used to guide nurses in the design and/or delivery of men's
health promotion programs.
PMID- 23156193
TI - Reaching adolescent girls through social networking: a new avenue for smoking
prevention messages.
AB - Because adolescent girls are being targeted on social networking sites by the
tobacco industry, new online tobacco control (TC) initiatives are needed. The
purpose of this interpretive descriptive study was to explore adolescent girls'
perspectives on the use of social networking sites to deliver TC messages
targeting young women. Focus groups were conducted with 17 girls aged 16 to 19.
Seven TC messages were provided for evaluation and as context for discussion
about the delivery of TC messages on social networking sites. Data were analyzed
for themes, which included concerns about the effectiveness of current TC
messages and the stereotypical representations of gender, factors perceived to
influence the effectiveness of TC messages on social networking sites, and
suggestions for enhancing the effectiveness of TC messages placed on social
networking sites. Endorsement of TC messaging on social networking sites suggests
that this medium is an untapped resource for smoking prevention.
PMID- 23156194
TI - Understanding gendered expectations and exemptions experienced by male double
duty caregivers: a qualitative secondary analysis.
AB - There is growing evidence that family caregivers who are also employed face
challenges in balancing the multiple demands associated with family caregiving.
Health professionals who are family caregivers, defined in this study as double
duty caregivers (DDCs), are expected to use their professional knowledge in the
provision of family care. The purpose of this qualitative secondary analysis was
to explore how gendered expectations and exemptions affect the caregiving
experiences and personal health of male nurses caring for family members. Being a
male DDC created intersecting gendered expectations and exemptions. These
coexisting and at times conflicting expectations and exemptions, constituted by
the overarching theme of the determinants of care, directly influenced the health
of male DDCs as they experienced tension when negotiating their dual role. The
findings have direct implications for health-care policy and practice, research,
and theory development.
PMID- 23156195
TI - Medication management for nurses working in long-term care.
AB - In long-term care (LTC), the complexity of residents' conditions and their
treatment requirements present challenges for nurses managing medications. The
purpose of this qualitative descriptive study was to explore medication
management as described by licensed nurses working in LTC. A total of 22 licensed
nurses from 2 LTC facilities located in the Canadian province of Ontario
participated in 4 focus groups. Thematic content analysis was used to organize
data into themes and a conceptual model was developed. The overarching theme was
that nurses are "racing against time" to manage medications and 3 subthemes
described how they coped with this important care process: preparing to race,
running the race, and finishing the race. Barriers to safe medication management
included time restraints, knowledge limitations, interruptions and distractions,
and poor communication. The findings can be used to better inform health-care
providers and to guide future research. They also have the potential to directly
impact outcomes related to safe medication management in LTC.
PMID- 23156196
TI - Metaphors and medication: understanding medication use by seniors in everyday
life.
AB - The purpose of this study was to explore the use of metaphor by independent
seniors taking medication for chronic health conditions. Narratives from a larger
study using grounded theory were analyzed using constant comparative analysis and
induction. A secondary analysis of the narratives of 21 participants was
undertaken. Transcripts were read line-by-line and all relevant language was
highlighted and reviewed with the aim of identifying relationships and themes.
The narratives revealed a diverse range of metaphoric language. Four categories
were identified: being shackled, hope, external authority, and communication
fears. Three additional themes were interwoven into the narratives: aging and
death, medication personified, and the body as object. The authors conclude that
metaphor reveals the tension and unresolved dilemmas faced by seniors with regard
to medication use.
PMID- 23156197
TI - Access to health care. Foreword.
PMID- 23156198
TI - Post-reform Medicaid before the court: discordant advocacy reflects conflicting
attitudes.
AB - This essay explores the conflicting positions taken by the United States in its
Medicaid-related briefs before the Supreme Court this October 2011 Term. In
Douglas v. Independent Living Center, the United States articulated a deferential
stance toward the states, a position consistent with longstanding states' rights
concerns in the Medicaid program. On the other hand, the federal government has
advocated a very broad view of federal authority under the spending power to
modify and expand Medicaid in Florida v. Health and Human Services. Congress has
acted in ways that are contradictory regarding Medicaid throughout the program's
history, and those conflicting attitudes have been accentuated by the executive
branch's dissonant litigation strategies this term. This essay posits that the
Court could minimize confusion with narrow holdings in both Douglas and Florida
v. HHS so as to allow Congress and HHS latitude to resolve their conflicting
attitudes toward Medicaid as well as the intricacies of conditional spending.
PMID- 23156199
TI - The challenges of reform for Medicaid managed care.
AB - This article explores the specific consequences to states as a result of
expansion of the Medicaid program under PPACA. Jane McCahill and Joseph Van Leer
explain the history of the Medicaid program, comparing and contrasting Medicaid
pre-PPACA with Medicaid post-PPACA. The authors examine the use of managed care
models by state Medicaid programs, describing the various forms of Medicaid
managed care employed by the states. The authors then detail the significant
changes resulting to Medicaid under PPACA. Finally, the article reviews the
Medicaid managed care program in Illinois specifically, focusing on reform of the
Illinois Medicaid program to be effectuated over the next few years. The authors
conclude by recommending mechanisms for integration among providers under the
managed care model in order to contain costs and achieve increased quality of
care.
PMID- 23156200
TI - New options to integrate care and financing for persons dually eligible for
Medicare and Medicaid.
AB - This paper reviews barriers to clinical and financial integration in services for
dual eligibles prior to passage of the ACA, identifies models used by states to
integrate care through contract and waiver authorities available to CMS prior to
passage of the ACA, describes two new demonstrations proposed by CMS through the
Medicare-Medicaid Coordination Office and Innovation Center, and discusses
several new models available for consideration by federal and state policymakers.
These options draw on experience from existing programs and waivers to provide
suggested changes to existing programs, as well as a permanent state plan option
for a fully integrated, capitated care model. This model could be made available
to states prior to the completion of the demonstration process begun by the
Medicare-Medicaid Coordination Office and Innovation Center.
PMID- 23156201
TI - Federal/state tensions in fulfilling Medicaid's purpose.
AB - Medicaid has been subject to reconsiderations of the proper role of government in
providing for the health and welfare of populations over recent decades. Over the
last decade in particular, a number of states have transferred many functions
that they once performed to private entities, including, in a number of cases,
express policymaking functions. The Patient Protection and Affordable Care Act
(ACA) takes some crucial steps towards readjusting the equilibrium of Medicaid.
Rather than further prioritizing the market in its reforms, it gives the federal
government stronger charge of Medicaid policy, refocusing the program more
directly on expanding eligibility and providing secure care for beneficiaries in
the process. I argue that this reprioritization is in better keeping with the
purpose of Medicaid, in contradistinction to the market-driven reforms undertaken
during the Bush administration and sought by some states today. It does, however,
shift more power from the states to the federal government. This has raised
concerns not only from states that oppose the new health reform law, but also
from a number that support it. These two groups of states share a desire for
greater flexibility in their Medicaid programs than the ACA permits. Yet only one
of these groups should be permitted to use federal Medicaid funds to make the
reforms they seek. Federal administrations need to be particularly careful, when
considering whether to grant state Medicaid waiver requests, to uphold Medicaid's
purpose of giving lower-income Americans genuine access to the same health care
that other Americans receive.
PMID- 23156202
TI - Acute effects of electro-acupuncture (EA) on hippocampal long term potentiation
(LTP) of perforant path-dentate gyrus granule cells synapse related to memory.
AB - Acupuncture, a traditional Chinese therapeutic method, has been widely used in
clinical practice to treat diseases such as stroke, Bell's palsy, Alzheimer
disease, Parkinson diseases, dysmenorrhea and chronic pain. Mounting lab data had
suggested that electro-acupuncture could alleviate dementia and restore long term
potentiation of hippocampus in rat. Clinical data also indicated that electro
acupuncture could improve electrical activity of brain in vascular dementia
patients. However, its biological basis and acute effects on hippocampal long
term potentiation (LTP) remain not well understood. Therefore, we sought to
investigate whether acute electro-acupuncture (acupoints: ST36 and SP6;
continuous wave, 2 mV, 2Hz; lasted 20 min) could enhance LTP of perforant path
dentate gyrus granule cells in anesthetized rat and explore its underlying
mechanisms. We found that electro-acupuncture could significantly increase PS2/PS
1 in pair pulse test (P <0.05, inter-pulse interval: 20ms and 90ms). When
compared to control group, electro-acupuncture could significantly enhance LTP to
about 234% which was about 143% of that in control group (P <0.05). It suggested
that electro-acupuncture could modulate the function of interneurons in
hippocampus hence increase LTP.
PMID- 23156203
TI - Sedating pediatric dental patients by oral ketamine with alternating bi-lateral
stimulation of eye movement desensitization and minimizing adverse reaction of
ketamine by acupuncture and Bi-Digital O-Ring Test.
AB - Ketamine, besides being an anesthetic agent, is also a strong analgesic that can
be especially useful for painful procedures. Vivid dreams and nightmare,
considered as undesirable side effects of ketamine, are rarely encountered when
administrated orally, making it one of the most desirable oral sedative for
children because it partially protects the pharyngeal-laryngeal reflex. Besides,
if used in recommended dosage, it does not suppress the cardiopulmonary function
as most other sedatives do. Ketamine's bronchodilator effect makes it a good
sedative for children with asthma, allergies, and hay fever. Alternating bi
lateral stimulation (ABLS) of eye movement desensitization, applying pre
operatively before ketamine was found to reduce the post-operative violent
emergence and behavioral problems. Acupressure at P 6 (Neikuan) acupoint helps to
decrease nausea and vomiting episodes by ketamine. 36 patients with history of
unmanageable behavior were sedated with ketamine 3mg/kg and ABLS. To prevent
possible adverse reaction, Bi-Digital O-Ring Test (BDORT) were used to test all
patients. ABLS significantly decreased tearful separation from parent. It took 15
to 20 minutes for ketamine to take effect, peak effect took 20 to 25 minutes.
Working time ranged from 20 to 40 minutes. Post-operative recovery was more
pleasant when ABLS was combined with ketamine, acupuncture/acupressure not only
prevented vomiting and BDORT safeguard the patients from unpredictable untoward
side effects but also promoting calmness.
PMID- 23156204
TI - Effects of combining electroacupuncture with general anesthesia induced by
sevoflurane in patients undergoing supratentorial craniotomy and improvements in
their clinical recovery profile & blood enkephalin.
AB - Drug-induced anesthesia combined with electroacupuncture (EA) in patients has
been put into practice in recent years in China. In this study, we showed the
effectiveness of EA on the speed of post-operative recovery of patients
undergoing supratentorial craniotomy and the potential clinical mechanism of EA.
Dual channel electrical stimulator made by HANS Beijing connected the following
acupoints respectively: LI4 (Hegu), SJ5 (Waiguan), ST36 (Zusanli), BL63 (Jinmen),
LR3 (Taichong), and GB40 (Qiuxu). Disperse-dense and symmetric biphasic pulse
waves were selected, frequency of waves (pulse rates) were 2Hz/100Hz,
altered/3sec; pulse duration was 0.6ms/0.2ms, 2Hz: 0.6ms, 100Hz: 0.2ms; symmetric
biphasic pulse wave. We found that the EA-group required 9.62% less sevoflurane
than the sham EA-group (P<0.05). During recovery from anesthesia, the autonomous
respiration recovery time, tracheo-tube removal time, eye-opening time, voluntary
motor recovery time, orientation force recovery time, and the operating-room
departure time of the EA-group were all significantly shortened 35.86%, 27.07%,
38.38%, 30.11%, 34.95%, 28.80% than the corresponding sham EA-group, respectively
(P<0.05). The serum enkephalin values were elevated in the EA group versus the
sham EA-group.
PMID- 23156205
TI - Algase's top 10 truths about publishing: a Letterman-esque guide for would-be
authors of journal articles.
PMID- 23156206
TI - Health inequities, HIV, and public health practice: examining the role of
qualitative research.
AB - Although communicable disease public health practice has traditionally been based
on numbers (e.g., incidence, prevalence), in the domain of HIV prevention and
control qualitative research has recently become a more commonly employed data
collection strategy. Of particular benefit, this approach can supplement the
numbers which typically underpin public health strategies by generating in-depth
understandings about how specific populations define, describe, and perceive
their health and the factors that affect it. However, the use of qualitative
research in public health must be explored; it cannot simply be accepted without
reflection or analysis. To guide such an investigation, the work of Michel
Foucault and Michael Hardt and Antonio Negri is used to examine two previous
research projects that were undertaken by the author. The outcome of this
analysis is the somewhat paradoxical conclusion that although qualitative
research can enhance public health work, it may also be a strategy that generates
the information that can be used for capturing and normalizing marginalized
populations. Qualitative research, in other words, may be a technique that can be
used to achieve biopolitical goals.
PMID- 23156207
TI - Do social support, stigma, and social problem-solving skills predict depressive
symptoms in people living with HIV? A mediation analysis.
AB - Social support, stigma, and social problem solving may be mediators of the
relationship between sign and symptom severity and depressive symptoms in people
living with HIV (PLWH). However, no published studies have examined these
individual variables as mediators in PLWH. This cross-sectional, correlational
study of 150 PLWH examined whether social support, stigma, and social problem
solving were mediators of the relationship between HIV-related sign and symptom
severity and depressive symptoms. Participants completed self-report
questionnaires during their visits at two HIV outpatient clinics in the
Southeastern United States. Using multiple regression analyses as a part of
mediation testing, social support, stigma, and social problem solving were found
to be partial mediators of the relationship between sign and symptom severity and
depressive symptoms, considered individually and as a set.
PMID- 23156208
TI - HIV/AIDS knowledge and self-efficacy among late adolescents in Nepal.
AB - The purpose of this study was to explore HIV/AIDS knowledge and self-efficacy for
limiting sexual risk behavior in Nepalese late adolescents attending college. A
convenience sample of 229 baccalaureate college students completed three
instruments: demographic, HIV/AIDS knowledge questions and the self-efficacy for
limiting sexual risk behavior questions. The findings of this study showed that
Nepalese youth had moderate HIV/AIDS knowledge and a moderate level of self
efficacy. However, they lacked knowledge in certain aspects of HIV transmission.
HIV/AIDS knowledge was strongly correlated with self-efficacy for limiting sexual
risk behavior. There was no statistical difference in HIV/AIDS knowledge and self
efficacy by gender. However, when each self-efficacy item was analyzed by gender,
there were significant differences in a few items by gender. ANOVA analysis
showed no significant differences on HIV/AIDS knowledge and self-efficacy by the
level of education. The findings of this study indicate that there is a need for
developing school-based and/or community-based programs that will increase
HIV/AIDS awareness among youth and help them develop decision making and
communication skills. It is also important to look at the school and college
curricula and integrate more HIV/AIDS information in the curriculum.
PMID- 23156209
TI - Caring in pediatric emergency nursing.
AB - An environment committed to providing family-centered care to children must be
aware of the nurse caring behaviors important to parents of children. This
descriptive study assessed the psychometrics of a revised version of the Caring
Behaviors Assessment (CBA) and examined nurse caring behaviors identified as
important to the parents of pediatric patients in a pediatric emergency
department. Jean Watson's theory of human caring provided the study's theoretical
underpinnings. The instrument psychometrics was determined through an index of
content validity (CVI) and internal consistency reliability. The instrument was
determined to be valid (CVI = 3.75) and reliable (Cronbach's alpha = .971). The
revised instrument was completed by a stratified, systematic random sample of 300
parents of pediatric emergency patients. Participants rated the importance of
each item for making the child feel cared for by nurses. Individual survey item
means were computed. Items with the highest means represented the most important
nurse caring behaviors. Leading nurse caring behaviors centered on carative
factors of "human needs assistance" and "sensitivity to self and others." Nearly
all nurse caring behaviors were important to the parents of pediatric patients,
although some behaviors were not priority. It is important for nurses to provide
family-centered care in a way that demonstrates nurse caring.
PMID- 23156210
TI - [Natural history, epidemiology and statistics of gynecologic cancers].
PMID- 23156211
TI - [Cancer prevention].
PMID- 23156212
TI - [History and current status of gynecologic cancer treatment].
PMID- 23156213
TI - [Registration of gynecologic malignancy in Japan].
PMID- 23156214
TI - [Survival for gynecological cancer patients in Osaka, Japan].
PMID- 23156215
TI - [Treatment guidelines in gynecologic malignancies].
PMID- 23156216
TI - [Board certified gynecologic oncologist in Japan].
PMID- 23156217
TI - [Cooperative researches for gynecologic cancers in Japan].
PMID- 23156219
TI - [Translational research].
PMID- 23156218
TI - [Current movement in global clinical trials--discussion at Gynecologic Cancer
Intergroup (GCIG)].
PMID- 23156220
TI - [Cervical cancer incidence: trends in Japan and world].
PMID- 23156221
TI - [The natural history of cervical cancer: what's a risk factor?].
PMID- 23156222
TI - [Mechanism of cervical carcinogenesis through expression of HPV oncoproteins].
PMID- 23156223
TI - [Genetic abnormality in cervical cancer].
PMID- 23156224
TI - [Analysis of clonality and HPV infection in benign, premalignant and malignant
lesions of the uterine cervix].
PMID- 23156225
TI - [Mechanism of metastasis in cervical cancer].
PMID- 23156226
TI - [Pathology of carcinomas of uterine cervix].
PMID- 23156227
TI - [Management of cervical intraepithelial neoplasia].
PMID- 23156228
TI - [Adenoma malignum and lobular endocervical glandular hyperplasia (LEGH)].
PMID- 23156229
TI - [New-concept: gastric-type adenocarcinoma of the uterine cervix].
PMID- 23156230
TI - [Clinical staging and treatment of cervical cancer].
PMID- 23156231
TI - [Pap smear and cervical cancer screening].
PMID- 23156232
TI - [Cervical cancer screening using HPV DNA testing and cytology].
PMID- 23156233
TI - [Genetic diagnosis: human papillomavirus (HPV) genotyping test].
PMID- 23156234
TI - [Colposcopy].
PMID- 23156235
TI - [Biopsy diagnosis of the cervical lesions].
PMID- 23156236
TI - [Tumor marker, biomarker].
PMID- 23156237
TI - [Imaging diagnosis of the uterine cervical carcinoma].
PMID- 23156238
TI - [HPV (human papillomavirus) vaccine].
PMID- 23156239
TI - [Development of new generation HPV vaccines: prophylactic and therapeutic].
PMID- 23156240
TI - [Cervical cancer treatment: current perspective].
PMID- 23156241
TI - [Surgical treatment for cervical cancer].
PMID- 23156242
TI - [Conization].
PMID- 23156243
TI - [Radical hysterectomy].
PMID- 23156244
TI - [Modified radical hysterectomy].
PMID- 23156245
TI - [Surgical treatment and function preservation in cervical cancer].
PMID- 23156246
TI - [Total laparoscopic radical hysterectomy--port reduction technique].
PMID- 23156247
TI - [Radical trachelectomy].
PMID- 23156248
TI - [Para-aortic lymph node (PAN) dissection for patients with the uterine cervical
cancer].
PMID- 23156249
TI - [Current status of sentinel lymph node biopsy in cervical cancer].
PMID- 23156250
TI - [The role of neoadjuvant chemotherapy for cervical cancer].
PMID- 23156251
TI - [Adjuvant chemotherapy for cervical cancer].
PMID- 23156252
TI - [Concurrent chemoradiotherapy (CCRT) in uterine cervical cancer].
PMID- 23156253
TI - [Treatment of recurrent cervical cancer].
PMID- 23156254
TI - [Treatment for adenocarcinoma and adenosquamous carcinoma of the uterine cervix].
PMID- 23156255
TI - [Treatments of small cell carcinoma of uterine cervix].
PMID- 23156256
TI - [Management and treatment for cervical cancer during pregnancy].
PMID- 23156257
TI - [Incidence of cancer of corpus, the trend in Japan and the world].
PMID- 23156258
TI - [Natural history and risk factors of endometrial carcinoma].
PMID- 23156259
TI - [Hereditary endometrial cancer and genetic testing].
PMID- 23156260
TI - [Effect of estrogen on molecular mechanisms of endometrial carcinogenesis].
PMID- 23156261
TI - [Genetic alterations of endometrial carcinoma].
PMID- 23156262
TI - [Biology of cancer stem cell in endometrial cancer].
PMID- 23156263
TI - [Mechanism of metastasis in endometrial cancer].
PMID- 23156264
TI - [Pathology and current topics on the selected histological types of endometrial
carcinoma].
PMID- 23156265
TI - [Precursors of the endometrial cancers].
PMID- 23156266
TI - [Atypical polypoid adenomyoma (APAM)].
PMID- 23156267
TI - [Clinical stage and therapy].
PMID- 23156268
TI - [Endometrial cytology for endometrial cancer screening].
PMID- 23156269
TI - [Ultrasound screening for endometrial carcinoma].
PMID- 23156270
TI - [Hysteroscopy].
PMID- 23156271
TI - [Histological diagnosis of endometrial cancer in biopsy specimen].
PMID- 23156272
TI - [Genetic diagnosis of the endometrial cancer].
PMID- 23156273
TI - [Clinical biomarkers of endometrial cancer].
PMID- 23156274
TI - [Diagnostic imaging of the endometrial carcinoma].
PMID- 23156275
TI - [A treatment strategy for endometrial cancer].
PMID- 23156276
TI - [Hormonal treatment of endometrial cancer].
PMID- 23156277
TI - [Introduction of the operative therapy].
PMID- 23156278
TI - [Laparoscopic surgery].
PMID- 23156279
TI - [Retroperitoneal lymphadenectomy in endometrial cancer].
PMID- 23156280
TI - [Sentinel lymph node detection in endometrial cancer].
PMID- 23156281
TI - [Role of chemotherapy in endometrial cancer].
PMID- 23156282
TI - [Neoadjuvant chemotherapy for endometrial cancer].
PMID- 23156283
TI - [Postoperative chemotherapy].
PMID- 23156284
TI - [Radiotherapy].
PMID- 23156285
TI - [Therapy of the recurrent endometrial cancer].
PMID- 23156286
TI - [Management for serous adenocarcinoma and clear cell adenocarcinoma of the
endometrium].
PMID- 23156287
TI - [Uterine carcinosarcoma].
PMID- 23156288
TI - [Diagnosis and treatment of endometrial stromal sarcoma].
PMID- 23156289
TI - [Diagnosis and treatment of uterine leiomyosarcoma].
PMID- 23156290
TI - [Epidemiological features of ovarian cancer in Japan and the world].
PMID- 23156291
TI - [Natural history and risk factors of ovarian cancer development].
PMID- 23156292
TI - [Clinical and genetic aspects of familial ovarian cancer].
PMID- 23156293
TI - [Molecular genetic of ovarian cancer].
PMID- 23156294
TI - [Genetic abnormalities in the pathogenesis of ovarian cancer].
PMID- 23156295
TI - [Biological characteristics of ovarian cancer].
PMID- 23156296
TI - [Malignant transformation of endometriosis].
PMID- 23156297
TI - [Molecular mechanisms of peritoneal dissemination in ovarian cancer].
PMID- 23156298
TI - [Metastasis related gene].
PMID- 23156299
TI - [Immunological aspect of metastasis of ovarian cancer].
PMID- 23156300
TI - [Pathology of ovarian cancer].
PMID- 23156301
TI - [Precursors of ovarian carcinoma and epithelial borderline tumors: current topics
in pathology].
PMID- 23156302
TI - [Synchronous primary ovarian and endometrial carcinomas].
PMID- 23156303
TI - [The general rules for clinical and pathological management of ovarian tumors
part 1: histological classification and color atlas of ovarian tumors].
PMID- 23156304
TI - [Staging for primary carcinoma of the ovary and treatment plan].
PMID- 23156305
TI - [Ovarian cancer screening].
PMID- 23156306
TI - [Clinical applications of ovarian cancer biomarkers].
PMID- 23156307
TI - [Diagnostic imaging of ovarian cancer].
PMID- 23156308
TI - [A practical approach to frozen-section diagnosis of ovarian tumors].
PMID- 23156309
TI - [Treatment overview of ovarian cancer].
PMID- 23156310
TI - [Overview of surgical treatment for ovarian cancer].
PMID- 23156311
TI - [Basic operation for ovarian cancer].
PMID- 23156312
TI - [Cytoreductive surgery in advanced epithelial ovarian cancer].
PMID- 23156313
TI - [Strategies and techniques for resection of upper abdominal disease in patients
with advanced ovarian cancer].
PMID- 23156314
TI - [Pelvic and para-aortic lymphadenectomy].
PMID- 23156315
TI - [Fertility-sparing surgery in epithelial ovarian cancer].
PMID- 23156316
TI - [Chemotherapy for ovarian cancer].
PMID- 23156317
TI - [Variation of primary chemotherapy for ovarian cancer].
PMID- 23156318
TI - [Chemotherapy for recurrent ovarian cancer].
PMID- 23156319
TI - [Intraperitoneal chemotherapy].
PMID- 23156320
TI - [Neoadjuvant chemotherapy].
PMID- 23156321
TI - [Molecular targeted therapies for epithelial ovarian cancer].
PMID- 23156322
TI - [Treatment of recurrent ovarian cancer].
PMID- 23156323
TI - [Treatment of clear cell adenocarcinoma and mucinous adenocarcinoma].
PMID- 23156324
TI - [Malignant germ cell tumor--outline].
PMID- 23156325
TI - [Operative treatment for the ovarian malignant germ tumor].
PMID- 23156326
TI - [Chemotherapy for ovarian malignant germ cell tumors].
PMID- 23156327
TI - [Current treatment strategy of sex cord--stromal tumors of the ovary by molecular
targeted therapy].
PMID- 23156328
TI - [Diagnosis and treatment for primary peritoneal cancer].
PMID- 23156329
TI - [Clinical management of fallopian tube cancer].
PMID- 23156330
TI - [Treatment for ovarian cancer during pregnancy].
PMID- 23156331
TI - [New FIGO staging for vulvar cancer].
PMID- 23156332
TI - [Vulvar cancer and vaginal cancer: precursor lesions and diagnoses].
PMID- 23156333
TI - [Treatment of vulvar and vaginal cancer].
PMID- 23156334
TI - [The general rules for clinical and pathological management of trophoblastic
diseases--2011, the 3rd edition].
PMID- 23156335
TI - [Recent changes in the incidence of gestational trophoblastic diseases in Japan].
PMID- 23156336
TI - [Ultrasonographic findings of early-stage hydatidiform mole].
PMID- 23156337
TI - [Pathologic diagnosis of hydatidiform mole].
PMID- 23156338
TI - [Genetic diagnosis of hydatidiform mole].
PMID- 23156339
TI - [Management of hydatidiform moles].
PMID- 23156340
TI - [Diagnosis and management of invasive mole].
PMID- 23156341
TI - [The diagnosis and treatment for choriocarcinoma].
PMID- 23156342
TI - [A twin pregnancy with hydatidiform mole and coexisting fetus].
PMID- 23156343
TI - [Diagnosis and treatment of placental site trophoblastic tumor].
PMID- 23156344
TI - [Diagnosis and treatment of epithelioid trophoblastic tumor].
PMID- 23156345
TI - [Recent advances in positron emission tomography (PET)].
PMID- 23156346
TI - [Thromboprophylaxis in the therapy for gynecological cancer].
PMID- 23156347
TI - [Robotic surgery in gynecological malignancies].
PMID- 23156348
TI - [Complications of surgery for gynecologic cancer].
PMID- 23156349
TI - [Palliative care of the patient with gynecologic cancer].
PMID- 23156350
TI - [Supportive care in sexuality and cancer related infertility for gynecological
cancer patients].
PMID- 23156351
TI - [Prevention and treatment for postoperative lymphorrhea and chylous ascites in
gynecologic malignancies].
PMID- 23156352
TI - [Lower-limb lymphedema after surgery for gynecologic cancer].
PMID- 23156353
TI - [Oral contraceptives as gynecological cancer prevention].
PMID- 23156354
TI - [Hormone replacement therapy and cancer risk].
PMID- 23156355
TI - [Application of assisted reproductive technology (ART) to patients with
gynecologic malignancy].
PMID- 23156356
TI - [Current status and the issues to be solved in Japanese children with diabetes
mellitus].
PMID- 23156357
TI - [Epidemiology of diabetes in children].
PMID- 23156358
TI - [Diagnostic criteria for childhood diabetes mellitus].
PMID- 23156359
TI - [Pathophysiology, diagnosis, and treatment of type 1 diabetes in children].
PMID- 23156360
TI - [Pathophysiology, diagnosis and treatment of type 2 diabetes mellitus in children
and adolescent].
PMID- 23156361
TI - [The pathophysiology, diagnosis, and treatment for neonatal diabetes mellitus].
PMID- 23156362
TI - [Prevention of pediatric diabetes].
PMID- 23156363
TI - [Transition from pediatric to adult diabetes care systems].
PMID- 23156364
TI - [Age-dependent alteration of energy and glucose metabolism].
PMID- 23156365
TI - [Clinical characteristics in elderly patients with type 2 diabetes mellitus].
PMID- 23156366
TI - [Current treatment and management of diabetes in elderly: introduction].
PMID- 23156367
TI - [Oral hypoglycemic treatment for elderly diabetics].
PMID- 23156368
TI - [Exercise and diet therapy for elderly patients with diabetes].
PMID- 23156369
TI - [Practical use of comprehensive geriatric assessment in the care of older
patients with diabetes mellitus].
PMID- 23156370
TI - [Management of diabetic elderly with cognitive impairment].
PMID- 23156371
TI - [Pathogenesis and concept of gestational diabetes mellitus].
PMID- 23156372
TI - [Epidemiology of gestational diabetes mellitus].
PMID- 23156373
TI - [Evidence-based medicine derived from HAPO study].
PMID- 23156374
TI - [Usefulness and problems of diagnostic criteria for gestational diabetes
mellitus].
PMID- 23156375
TI - [Keynote of management and treatment for gestational diabetes mellitus].
PMID- 23156376
TI - [Ways of preventing diabetes in mothers and children].
PMID- 23156377
TI - [Follow-up of women with previous gestational diabetes mellitus].
PMID- 23156378
TI - [Management of women with preexisting diabetes mellitus].
PMID- 23156379
TI - [Treatment of hypertension in diabetic patients associated with hypertension].
PMID- 23156380
TI - [Diabetes mellitus with dyslipidemia].
PMID- 23156381
TI - [Diabetes with obesity].
PMID- 23156382
TI - [Pathophysiology and therapeutic procedures for diabetes in Cushing syndrome].
PMID- 23156383
TI - [Acromegaly].
PMID- 23156384
TI - [Pheochromocytoma].
PMID- 23156385
TI - [Glucagonoma].
PMID- 23156386
TI - [Pancreatic diabetes].
PMID- 23156387
TI - [Glucose intolerance in chronic liver disease].
PMID- 23156388
TI - [Drug-induced diabetes mellitus].
PMID- 23156389
TI - [Insulin autoimmune syndrome].
PMID- 23156390
TI - [Lipoatrophic diabetes].
PMID- 23156391
TI - [Insulin gene mutations].
PMID- 23156392
TI - [Mutations in the insulin receptor gene].
PMID- 23156393
TI - [Mitochondrial DNA mutation].
PMID- 23156394
TI - [MODY(maturity onset diabetes of the young)].
PMID- 23156395
TI - [Hereditary syndrome associated with diabetes mellitus].
PMID- 23156396
TI - [The present situation and future problems on diabetic complications in Japan].
PMID- 23156397
TI - [Genetic study for diabetic microvascular complications--recent advances and
future perspectives].
PMID- 23156398
TI - [Polyol-, hexosamine pathway and protein C kinase activation in the pathogenesis
of diabetic complications].
PMID- 23156399
TI - [Role of oxidative stress in pathogenesis of diabetic complications].
PMID- 23156400
TI - [Endothelial dysfunction].
PMID- 23156401
TI - [Role of advanced glycation end products (AGE) and soluble receptor for AGE
(sRAGE) in vascular complications in diabetes].
PMID- 23156402
TI - [Involvement of chronic inflammation in chronic diseases and diabetic
complications].
PMID- 23156403
TI - [Pathophysiological role of renin-angiotensin-aldosterone system in the
development of diabetic complication].
PMID- 23156404
TI - [Hypertension and abnormal lipid metabolism].
PMID- 23156405
TI - [Therapeutic strategy in diabetes for the prevention of its complications].
PMID- 23156406
TI - [Effect of glycemic control on development and progression of diabetic
complication].
PMID- 23156407
TI - [Treatment of hypertension].
PMID- 23156409
TI - [Acute complications of diabetes].
PMID- 23156408
TI - [Meaning of dyslipidemia management in diabetes].
PMID- 23156410
TI - [Characteristics of diabetic macroangiopathy in Japan and East Asia].
PMID- 23156411
TI - [Diabetes mellitus and cerebrovascular diseases].
PMID- 23156412
TI - [Clinical aspects of diabetic coronary].
PMID- 23156413
TI - [Diagnosis and treatment for peripheral arterial disease].
PMID- 23156414
TI - [Epidemiology of diabetic retinopathy].
PMID- 23156415
TI - [Large clinical studies on diabetic retinopathy].
PMID- 23156416
TI - [Etiology of diabetic retinopathy].
PMID- 23156417
TI - [Classification of diabetic retinopathy].
PMID- 23156418
TI - [Pathophysiology and diagnosis of diabetic retinopathy].
PMID- 23156419
TI - [Medical treatment for diabetic retinopathy].
PMID- 23156420
TI - [Vitrectomy for the treatment of diabetic retinopathy].
PMID- 23156421
TI - [Trends in drug development for diabetic retinopathy].
PMID- 23156422
TI - [Other ocular complications related to diabetes mellitus].
PMID- 23156423
TI - [Strategy for prevention from development and progression of diabetic
retinopathy].
PMID- 23156424
TI - [Epidemiology of diabetic nephropathy].
PMID- 23156425
TI - [Pathogenesis of diabetic nephropathy: the role of inflammation].
PMID- 23156426
TI - [Classification of diabetic nephropathy by Japanese Society of Nephrology and
Japanse Diabetes Society and KDIGO CKD staging].
PMID- 23156427
TI - [Pathology of diabetic nephropathy].
PMID- 23156428
TI - [Pathogenesis and diagnosis of diabetic nephropathy].
PMID- 23156429
TI - [Current therapy in diabetic patients with nephropathy].
PMID- 23156430
TI - [Significance of RAAS inhibition in diabetic nephropathy].
PMID- 23156431
TI - [iPS cell technology-based strategies for the treatment of diabetic nephropathy].
PMID- 23156432
TI - [Registry system of diabetic nephropathy in Japan].
PMID- 23156433
TI - [Epidemiology of diabetic neuropathy].
PMID- 23156434
TI - [Pathogenesis of diabetic neuropathy].
PMID- 23156435
TI - [Classification of diabetic neuropathy and clinical staging of diabetic
polyneuropathy--current understanding].
PMID- 23156436
TI - [Pathophysiology, neurological examinations and diagnosis of diabetic
polyneuropathy].
PMID- 23156437
TI - [Recent advances in treatment of diabetic polyneuropathy].
PMID- 23156438
TI - [Clinical epidemiology of diabetic foot].
PMID- 23156439
TI - [Pathogenesis of diabetic foot].
PMID- 23156440
TI - [Preventive footcare for the occurrence and progress of the diabetic foot].
PMID- 23156441
TI - [Management of diabetic-foot lesions from the view point of internal medicine].
PMID- 23156442
TI - [Surgical treatment and topical wound management for diabetic foot].
PMID- 23156443
TI - [Usefulness and problems of maggot therapy in Japan].
PMID- 23156444
TI - [Regenerative medicine (cell therapy) for diabetic ulcer].
PMID- 23156445
TI - [Periodontal disease].
PMID- 23156446
TI - [Dementia in diabetes mellitus: preventive strategy].
PMID- 23156447
TI - [Infectious disease associated with diabetes mellitus--mechanisms,
classification, diagnosis and therapy].
PMID- 23156448
TI - [Osteoporosis].
PMID- 23156449
TI - [Sleep disorder, sleep disordered breathing].
PMID- 23156450
TI - [Erectile dysfunction].
PMID- 23156451
TI - [Diabetes mellitus and major depressive disorder].
PMID- 23156452
TI - [NAFLD, NASH].
PMID- 23156453
TI - [Chronic obstructive pulmonary disease (COPD)].
PMID- 23156454
TI - [Revascularization for peripheral arterial disease in diabetic patients].
PMID- 23156455
TI - [Systematic review of cancer risk in diabetes mellitus].
PMID- 23156456
TI - [Diabetes and cancer risk: evidence from large-scale prospective study].
PMID- 23156457
TI - [Insulin, IGF-I and cancer].
PMID- 23156458
TI - [Relation between adiponectin/AdipoR and cancer in diabetes mellitus].
PMID- 23156459
TI - [Diabetes and pancreatic cancer].
PMID- 23156460
TI - [Impact of diabetes mellitus on hepatocellular carcinoma].
PMID- 23156461
TI - [Diabetes and colorectal cancer].
PMID- 23156462
TI - [Diabetes mellitus and the risk of gastric cancer].
PMID- 23156463
TI - [Diabetes mellitus and prostate cancer].
PMID- 23156464
TI - [Diabetes mellitus and women's cancer].
PMID- 23156465
TI - [Management of patients with diabetes mellitus by using clinical path].
PMID- 23156466
TI - [Medical relationship between the hospital and clinics about diabetic patients].
PMID- 23156467
TI - [Improvement of quality of diabetes care with EHR and regional disease management
mapping system].
PMID- 23156468
TI - [American Association of Diabetes Educators, the current DSME (diabetes self
management education) standards].
PMID- 23156469
TI - [Insulin injection and patient education].
PMID- 23156470
TI - [Clinical usefulness of educational admission in diabetes mellitus].
PMID- 23156471
TI - [Psychoeducation on the people with diabetes--how do we support diabetic patients
with psychological burden?].
PMID- 23156472
TI - [Circadian rhythm and diabetes].
PMID- 23156473
TI - [Hyperadiponectinemia and longevity].
PMID- 23156474
TI - [Roles of sportology for the prevention of diabetes mellitus].
PMID- 23156475
TI - [Current status and awaiting solution of training system of Board Certified
Diabetologists of the Japan Diabetes Society].
PMID- 23156476
TI - [Medical economy in the treatment of diabetes and its problems].
PMID- 23156477
TI - [The pathophysiology, diagnosis, and treatment for neonatal hypoglycemia].
PMID- 23156478
TI - [Hypoglycemia and cognitive impairment in diabetes mellitus].
PMID- 23156479
TI - [Classification and mechanism of adverse drug reaction].
PMID- 23156480
TI - [Factors affecting the occurrence of adverse drug reaction].
PMID- 23156481
TI - [Pharmacogenomics for adverse drug reactions].
PMID- 23156482
TI - [Diagnosis on adverse drug reactions].
PMID- 23156483
TI - [Reporting system for adverse drug reactions and infections].
PMID- 23156484
TI - [Classification criteria for severity of adverse drug reactions].
PMID- 23156485
TI - [Precautions for use].
PMID- 23156486
TI - [Relief system for adverse drug reactions].
PMID- 23156487
TI - [Drug-induced liver injury].
PMID- 23156488
TI - [Drug-induced nephropathy].
PMID- 23156489
TI - [Drug induced hematological disorders].
PMID- 23156490
TI - [Adverse effects of medicinal drugs to the skin].
PMID- 23156491
TI - [Respiratory disorders].
PMID- 23156492
TI - [Gastrointestinal disorder].
PMID- 23156493
TI - [Drug-induced cardiotoxicity].
PMID- 23156494
TI - [Psychotic disorder].
PMID- 23156495
TI - [Neuromuscular side effects].
PMID- 23156496
TI - [Drug-induced metabolic and endocrine disorders].
PMID- 23156497
TI - [Fluid and electrolyte disturbances].
PMID- 23156499
TI - [Adverse drug reactions of antiviral agents].
PMID- 23156498
TI - [Antibiotics].
PMID- 23156500
TI - [Myelosuppression].
PMID- 23156501
TI - [Gastrointestinal complication of cancer chemotherapy].
PMID- 23156502
TI - [Lung injury].
PMID- 23156503
TI - [Skin toxicity, alopecia].
PMID- 23156504
TI - [Glucocorticoid].
PMID- 23156505
TI - [Nonsteroidal anti-inflammatory drugs].
PMID- 23156506
TI - [Anti-rheumatic drugs].
PMID- 23156507
TI - [Insulin preparation].
PMID- 23156508
TI - [Adverse effects of insulin secretagogues (sulfonylureas and glinides)].
PMID- 23156509
TI - [DPP-4 inhibitors and GLP-1 receptor agonists].
PMID- 23156510
TI - [Biguanide, pioglitazone and alpha-glucosidase inhibitors].
PMID- 23156511
TI - [Medicines for dyslipidemia].
PMID- 23156512
TI - [Hormone replacement therapy].
PMID- 23156513
TI - [Side-effects of therapeutic agents for osteoporosis].
PMID- 23156514
TI - [Antithrombotic agents].
PMID- 23156515
TI - [Adverse effects of cardiovascular agents in Japan--update 2012].
PMID- 23156516
TI - [Calcium antagonists, diuretics, beta-blockers and alpha-blockers].
PMID- 23156517
TI - [ACE inhibitor, ARB, renin inhibitor].
PMID- 23156518
TI - [Side effects of bronchodilator and asthma medications].
PMID- 23156519
TI - [Adverse effects of drugs for peptic ulcer diseases].
PMID- 23156520
TI - [Medicines for liver diseases; interferon preparations and anti-hepatitis virus
agents].
PMID- 23156521
TI - [Adverse events of antipsychotics, antidepressants, mood stabilizers,
antiepileptics, and psychostimulants].
PMID- 23156522
TI - [Anxiolytics, hypnotics].
PMID- 23156523
TI - [Anti-dementia drugs].
PMID- 23156524
TI - [Side effects of Kampo extracts and patient compliance instruction].
PMID- 23156525
TI - [Adverse events of vaccine].
PMID- 23156526
TI - [Clinically important drug interactions].
PMID- 23156527
TI - [Interactions of drug and nutrient].
PMID- 23156528
TI - [Infants and children].
PMID- 23156529
TI - [Drugs in pregnancy and lactation].
PMID- 23156530
TI - [Adverse drug effects in elderly patients].
PMID- 23156531
TI - [Management of adverse drug reaction on the patients with allergic diseases].
PMID- 23156532
TI - [The case to the patient with renal insufficiency].
PMID- 23156533
TI - [Anaphylaxis].
PMID- 23156534
TI - [Angioedema].
PMID- 23156535
TI - [Laryngeal edema].
PMID- 23156536
TI - [Abnormality of liver functional test].
PMID- 23156537
TI - [Drug-induced cholestasis].
PMID- 23156538
TI - [Hepatitis].
PMID- 23156539
TI - [Fulminant hepatitis].
PMID- 23156540
TI - [Tubulointerstitial nephritis associated with drug reactions].
PMID- 23156541
TI - [Acute kidney injury: AKI].
PMID- 23156542
TI - [Drug-induced nephrotic syndrome].
PMID- 23156543
TI - [Tumor lysis syndrome].
PMID- 23156544
TI - [Urinary retention, voiding difficulty].
PMID- 23156545
TI - [Hemorrhagic cystitis].
PMID- 23156546
TI - [Aplastic anemia associated with drug].
PMID- 23156547
TI - [Agranulocytosis (neutropenia)].
PMID- 23156548
TI - [Thrombocytopenia].
PMID- 23156549
TI - [Drug induced thrombotic thrombocytopenic purpura].
PMID- 23156550
TI - [Heparin-induced thrombocytopenia (HIT)].
PMID- 23156551
TI - [Thrombosis--adverse effect of drugs].
PMID- 23156552
TI - [Coagulation disorder].
PMID- 23156553
TI - [Disseminated intravascular coagulation (DIC)].
PMID- 23156555
TI - [Drug and anemia].
PMID- 23156554
TI - [Bleeding tendency].
PMID- 23156556
TI - [Acute generalized exanthematous pustulosis].
PMID- 23156557
TI - [Stevens-Johnson syndrome/toxic epidermal necrolysis].
PMID- 23156558
TI - [Drug-induced hypersensitivity syndrome].
PMID- 23156559
TI - [Drug-induced urticaria].
PMID- 23156560
TI - [Contact dermatitis].
PMID- 23156561
TI - [Hand-foot syndrome].
PMID- 23156562
TI - [Drug-induced interstitial lung disease].
PMID- 23156563
TI - [Acute eosinophilic pneumonia, eosinophilic pneumonia].
PMID- 23156564
TI - [Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS)].
PMID- 23156565
TI - [Drug-induced pleural diseases].
PMID- 23156566
TI - [Respiratory depression].
PMID- 23156567
TI - [Drug-induced pulmonary edema].
PMID- 23156568
TI - [Drug-induced diffuse alveolar hemorrhage].
PMID- 23156569
TI - [Aspirin-intolerant asthma].
PMID- 23156570
TI - [Peptic ulcer (gastro-duodenal ulcer, acute gastric mucosal lesion, NSAIDs
induced ulcer)].
PMID- 23156571
TI - [Paralytic ileus].
PMID- 23156572
TI - [Pseudomembranous colitis].
PMID- 23156573
TI - [Severe diarrhea].
PMID- 23156575
TI - [Stomatitis medicamentosa].
PMID- 23156574
TI - [Drug-induced acute pancreatitis].
PMID- 23156576
TI - [Congestive heart failure].
PMID- 23156577
TI - [Ventricular tachycardia].
PMID- 23156578
TI - [Drug-induced myocarditis and cardiomyopathy].
PMID- 23156579
TI - [Arrhythmogenicity].
PMID- 23156580
TI - [Drug dependence syndrome as a side effect of medical drug use].
PMID- 23156581
TI - [Drug-induced abnormal behaviors].
PMID- 23156582
TI - [Drug-induced depression].
PMID- 23156583
TI - [Neuroleptic malignant syndrome (NMS)].
PMID- 23156584
TI - [Serotonin syndrome].
PMID- 23156585
TI - [Suicidal thinking and behavior].
PMID- 23156586
TI - [Neonatal withdrawal syndrome or neonatal abstinence syndrome].
PMID- 23156587
TI - [Ataxia].
PMID- 23156588
TI - [Guillain-Barre syndrome].
PMID- 23156589
TI - [Convulsions, epilepsy].
PMID- 23156590
TI - [Dyskinesia].
PMID- 23156591
TI - [Drug-induced leukoencephalopathy].
PMID- 23156592
TI - [Drug induced peripheral neuropathy].
PMID- 23156593
TI - [Drug induced parkinsonism].
PMID- 23156594
TI - [Drug-induced aseptic meningitis].
PMID- 23156595
TI - [Drug-related acute encephalopathy in childhood].
PMID- 23156596
TI - [Rhabdomyolysis].
PMID- 23156597
TI - [Malignant hyperthermia].
PMID- 23156598
TI - [Visual disturbance].
PMID- 23156599
TI - [Hearing loss].
PMID- 23156600
TI - [Taste disorder].
PMID- 23156601
TI - [Hypoglycemia].
PMID- 23156602
TI - [Hyperglycemia].
PMID- 23156603
TI - [SIADH].
PMID- 23156604
TI - [Pseudoaldosteronism].
PMID- 23156605
TI - [Hypothyroidism].
PMID- 23156606
TI - [Drug induced thyrotoxicosis].
PMID- 23156607
TI - [Drug-induced osteoporosis].
PMID- 23156608
TI - [Bisphosphonate-related osteonecrosis of the jaws].
PMID- 23156609
TI - [Idiopathic osteonecrosis of the femoral head].
PMID- 23156610
TI - [Ovarian hyperstimulation syndrome].
PMID- 23156611
TI - [Adverse events of molecular targeting drugs in oncology].
PMID- 23156612
TI - [High-risk drugs].
PMID- 23156613
TI - [Instruction of adverse drug reaction to patient].
PMID- 23156614
TI - Preface to the special section on human factors and automation in vehicles:
designing highly automated vehicles with the driver in mind.
AB - OBJECTIVE: This special section brings together diverse research regarding driver
interaction with advanced automotive technology to guide design of increasingly
automated vehicles. BACKGROUND: Rapidly evolving vehicle automation will likely
change cars and trucks more in the next 5 years than the preceding 50, radically
redefining what it means to drive. METHOD: This special section includes 10
articles from European and North American researchers reporting simulator and
naturalistic driving studies. RESULTS: Little research has considered the
consequences of fully automated driving, with most focusing on lane-keeping and
speed control systems individually. The studies reveal two underlying design
philosophies: automate driving versus support driving. Results of several
studies, consistent with previous research in other domains, suggest that the
automate philosophy can delay driver responses to incidents in which the driver
has to intervene and take control from the automation. Understanding how to
orchestrate the transfer or sharing of control between the system and the driver,
particularly in critical incidents, emerges as a central challenge. CONCLUSION:
Designers should not assume that automation can substitute seamlessly for a human
driver, nor can they assume that the driver can safely accommodate the
limitations of automation. Designers, policy makers, and researchers must give
careful consideration to what role the person should have in highly automated
vehicles and how to support the driver if the driver is to be responsible for
vehicle control. As in other domains, driving safety increasingly depends on the
combined performance of the human and automation, and successful designs will
depend on recognizing and supporting the new roles of the driver.
PMID- 23156615
TI - Heavy-truck drivers' following behavior with intervention of an integrated, in
vehicle crash warning system: a field evaluation.
AB - OBJECTIVE: This study is designed to evaluate heavy-truck drivers' following
behavior and how a crash warning system influences their headway maintenance.
BACKGROUND: Rear-end crashes are one of the major crash types involving heavy
trucks and are more likely than other crash types to result in fatalities.
Previous studies have observed positive effects of in-vehicle crash warning
systems in passenger car drivers. Although heavy-truck drivers are generally more
experienced, driver-related errors are still the leading factors contributing to
heavy-truck-related rear-end crashes. METHOD: Data from a 10-month naturalistic
driving study were used. Participants were 18 professional heavy-truck drivers
who received warnings during the last 8 months of the study (treatment period)
but not during the first 2 months (baseline period). Time headway and driver's
brake reaction time were extracted and compared with condition variables,
including one between-subjects variable (driver shift) and five within-subjects
variables (treatment condition, roadway types, traffic density, wiper state, and
trailer configuration). RESULTS: The presence of warnings resulted in a 0.28-s
increase of mean time headway with dense on-road traffic and a 0.20-s increase
with wipers on. Drivers also responded to the forward conflicts significantly
faster (by 0.26 s, a 15% enhancement) in the treatment condition compared with
responses in the baseline condition. CONCLUSION: Positive effects on heavy-truck
drivers' following performance were observed with the warning system.
APPLICATION: The installation of such in-vehicle crash warning systems can help
heavy-truck drivers keep longer headway distances in challenging situations and
respond quicker to potential traffic conflicts, therefore possibly increasing
heavy-truck longitudinal driving safety.
PMID- 23156616
TI - Driving with a partially autonomous forward collision warning system: how do
drivers react?
AB - OBJECTIVE: The effects of a forward collision warning (FCW) and braking system
(FCW+) were examined in a driving simulator study analyzing driving and gaze
behavior and the engagement in a secondary task. BACKGROUND: In-depth accident
analyses indicate that a lack of appropriate expectations for possible critical
situations and visual distraction may be the major causes of rear-end crashes.
Studies with FCW systems have shown that a warning alone was not enough for a
driver to be able to avoid the accident. Thus,an additional braking intervention
by such systems could be necessary. METHOD: In a driving simulator experiment, 30
drivers took part in a car-following scenario in an urban area. It was assumed
that different lead car behaviors and environmental aspects would lead to
different drivers' expectations of the future traffic situation. Driving with and
without FCW+ was introduced as a between-subjects factor. RESULTS: Driving with
FCW+ resulted in significantly fewer accidents in critical situations. This
result was achieved by the system's earlier reaction time as compared with that
of drivers. The analysis of the gaze behavior showed that driving with the system
did not lead to a stronger involvement in secondary tasks. CONCLUSION: The study
supports the hypotheses about the importance of missing expectations for the
occurrence of accidents. These accidents can be prevented by an FCW+ that brakes
autonomously. APPLICATION: The results indicate that an autonomous braking
intervention should be implemented in FCW systems to increase the effectiveness
of these assistance systems.
PMID- 23156617
TI - Simulator training with a forward collision warning system: effects on driver
system interactions and driver trust.
AB - OBJECTIVE: The study addressed the role of familiarization on a driving simulator
with a forward collision warning (FCW) and investigated its impact on driver
behavior. BACKGROUND: Drivers need a good understanding of how an FCW system
functions to trust it and use it properly. Theoretical and empirical data suggest
that exploring the capacities and limitations of the FCW during the learning
period improves operating knowledge and leads to increased driver trust in the
system and better driver-system interactions.The authors tested this hypothesis
by comparing groups of drivers differing in FCW familiarity. METHOD: During the
familiarization phase, familiarized drivers were trained on the simulator using
the FCW, unfamiliarized drivers simply read an FCW manual, and control drivers
had no contact with the FCW. During the test, drivers drove the simulator and had
to interact with traffic; both familiarized and unfamiliarized drivers used the
FCW, whereas controls did not. RESULTS: Simulator familiarization improved driver
understanding of FCW operation. Driver-system interactions were more effective:
Familiarized drivers had no collisions, longer time headways, and better
reactions in most situations. Familiarization increased trust in the FCW but did
not raise system acceptance. CONCLUSION: Familiarization on the simulator had a
positive effect on driver-system interactions and on trust in the system. The
limitations of the familiarization method are discussed in relation to the
driving simulator methodology. APPLICATION: Practicing on a driving simulator
with driving-assistance systems could facilitate their use during real driving.
PMID- 23156618
TI - Use patterns among early adopters of adaptive cruise control.
AB - OBJECTIVE: The objective of this study was to investigate use patterns among
early adopters of adaptive cruise control (ACC). BACKGROUND: Extended use ofACC
may influence a driver's behavior in the long-term, which can have unintended
safety consequences. METHOD: The authors examined the use of a motion-based
simulator by 24 participants (15 males and 9 females). Cluster analysis was
performed on drivers' use of ACC and was based on their gap settings, speed
settings, number of warnings issued, and ACC disengaged. The data were then
examined on the basis of driving performance measures and drivers' subjective
responses to trust in ACC, understanding of system operations, and driving
styles. Driving performance measures included minimum time headway, adjusted
minimum time to collision, and drivers' reaction time to critical events.
RESULTS: Three groups of drivers were observed on the basis of risky behavior,
moderately risky behavior, and conservative behavior. Drivers in the conservative
group stayed farther behind the lead vehicle than did drivers in the other two
groups. Risky drivers responded later to critical events and had more ACC
warnings issued. CONCLUSION: Safety consequences with ACC may be more prevalent
in some driver groups than others. The findings suggest that these safety
implications are related to trust in automation, driving styles, understanding of
system operations, and personalities. APPLICATION: Potential applications of this
research include enhanced design for next-generation ACC systems and
countermeasures to improve safe driving with ACC.
PMID- 23156619
TI - Fatigue and voluntary utilization of automation in simulated driving.
AB - OBJECTIVE: A driving simulator was used to assess the impact on fatigue, stress,
and workload of full vehicle automation that was initiated by the driver.
BACKGROUND: Previous studies have shown that mandatory use of full automation
induces a state of "passive fatigue" associated with loss of alertness. By
contrast, voluntary use of automation may enhance the driver's perceptions of
control and ability to manage fatigue. METHOD: Participants were assigned to one
of two experimental conditions, automation optional (AO) and nonautomation (NA),
and then performed a 35 min, monotonous simulated drive. In the last 5 min,
automation was unavailable and drivers were required to respond to an emergency
event. Subjective state and workload were evaluated before and after the drive.
RESULTS: Making automation available to the driver failed to alleviate fatigue
and stress states induced by driving in monotonous conditions. Drivers who were
fatigued prior to the drive were more likely to choose to use automation, but
automation use increased distress, especially in fatigue-prone drivers. Drivers
in the AO condition were slower to initiate steering responses to the emergency
event, suggesting optional automation may be distracting. CONCLUSION: Optional,
driver-controlled automation appears to pose the same dangers to task engagement
and alertness as externally initiated automation. APPLICATION: Drivers of
automated vehicles may be vulnerable to fatigue that persists when normal vehicle
control is restored. It is important to evaluate automated systems' impact on
driver fatigue, to seek design solutions to the issue of maintaining driver
engagement, and to address the vulnerabilities of fatigue-prone drivers.
PMID- 23156620
TI - Control task substitution in semiautomated driving: does it matter what aspects
are automated?
AB - OBJECTIVE: The study was designed to show how driver attention to the road scene
and engagement of a choice of secondary tasks are affected by the level of
automation provided to assist or take over the basic task of vehicle control. It
was also designed to investigate the difference between support in longitudinal
control and support in lateral control. BACKGROUND: There is comparatively little
literature on the implications of automation for drivers' engagement in the
driving task and for their willingness to engage in non-driving-related
activities. METHOD: A study was carried out on a high-level driving simulator in
which drivers experienced three levels of automation: manual driving,
semiautomated driving with either longitudinal or lateral control provided, and
highly automated driving with both longitudinal and lateral control provided.
Drivers were free to pay attention to the roadway and traffic or to engage in a
range of entertainment and grooming tasks. RESULTS: Engagement in the nondriving
tasks increased from manual to semiautomated driving and increased further with
highly automated driving. There were substantial differences in attention to the
road and traffic between the two types of semiautomated driving. CONCLUSION: The
literature on automation and the various task analyses of driving do not
currently help to explain the effects that were found. Lateral support and
longitudinal support may be the same in terms of levels of automation but appear
to be regarded rather differently by drivers.
PMID- 23156621
TI - Highly automated driving, secondary task performance, and driver state.
AB - OBJECTIVE: A driving simulator study compared the effect of changes in workload
on performance in manual and highly automated driving. Changes in driver state
were also observed by examining variations in blink patterns. BACKGROUND: With
the addition of a greater number of advanced driver assistance systems in
vehicles, the driver's role is likely to alter in the future from an operator in
manual driving to a supervisor of highly automated cars. Understanding the
implications of such advancements on drivers and road safety is important.
METHOD: A total of 50 participants were recruited for this study and drove the
simulator in both manual and highly automated mode. As well as comparing the
effect of adjustments in driving-related workload on performance, the effect of a
secondary Twenty Questions Task was also investigated. RESULTS: In the absence of
the secondary task, drivers' response to critical incidents was similar in manual
and highly automated driving conditions. The worst performance was observed when
drivers were required to regain control of driving in the automated mode while
distracted by the secondary task. Blink frequency patterns were more consistent
for manual than automated driving but were generally suppressed during conditions
of high workload. CONCLUSION: Highly automated driving did not have a deleterious
effect on driver performance, when attention was not diverted to the distracting
secondary task. APPLICATION: As the number of systems implemented in cars
increases, an understanding of the implications of such automation on drivers'
situation awareness, workload, and ability to remain engaged with the driving
task is important.
PMID- 23156622
TI - An adaptive driver support system: user experiences and driving performance in a
simulator.
AB - OBJECTIVE: The aim of this study was to test the implementation of an adaptive
driver support system. BACKGROUND: Providing support might not always be
desirable from a safety perspective, as support may lead to problems related to a
human operator being out of the loop. In contrast, adaptive support systems are
designed to keep the operator in the loop as much as possible by providing
support only when necessary. METHOD: A total of 31 experienced drivers were
exposed to three modes of lane-keeping support nonadaptive, adaptive, and no
support. Support involved continuously updated lateral position feedback shown on
a head-up display. When adaptive, support was triggered by performance-based
indications of effort investment. Narrowing lane width and increasing density of
oncoming traffic served to increase steering demand, and speed was fixed in all
conditions to prevent any compensatory speed reactions. RESULTS: Participants
preferred the adaptive support mode mainly as a warning signal and tended to
ignore nonadaptive feedback. Furthermore, driving behavior was improved by
adaptive support in that participants drove more centrally, displayed less
lateral variation and drove less outside the lane's delineation when support was
in the adaptive mode compared with both the no-support mode and the nonadaptive
support mode. CONCLUSION: A human operator is likely to use machine-triggered
adaptations as an indication that thresholds have been passed, regardless of the
support that is initiated. Therefore supporting only the sensory processing stage
of the human information processing system with adaptive automation may not
feasible. APPLICATION: These conclusions are relevant for designing adaptive
driver support systems.
PMID- 23156623
TI - Sharing control with haptics: seamless driver support from manual to automatic
control.
AB - OBJECTIVE: Haptic shared control was investigated as a human-machine interface
that can intuitively share control between drivers and an automatic controller
for curve negotiation. BACKGROUND: As long as automation systems are not fully
reliable, a role remains for the driver to be vigilant to the system and the
environment to catch any automation errors. The conventional binary switches
between supervisory and manual control has many known issues, and haptic shared
control is a promising alternative. METHOD: A total of 42 respondents of varying
age and driving experience participated in a driving experiment in a fixed-base
simulator, in which curve negotiation behavior during shared control was compared
to during manual control, as well as to three haptic tunings of an automatic
controller without driver intervention. RESULTS: Under the experimental
conditions studied, the main beneficial effect of haptic shared control compared
to manual control was that less control activity (16% in steering wheel reversal
rate, 15% in standard deviation of steering wheel angle) was needed for realizing
an improved safety performance (e.g., 11% in peak lateral error). Full automation
removed the need for any human control activity and improved safety performance
(e.g., 35% in peak lateral error) but put the human in a supervisory position.
CONCLUSION: Haptic shared control kept the driver in the loop, with enhanced
performance at reduced control activity, mitigating the known issues that plague
full automation. APPLICATION: Haptic support for vehicular control ultimately
seeks to intuitively combine human intelligence and creativity with the benefits
of automation systems.
PMID- 23156624
TI - Trust in smart systems: sharing driving goals and giving information to increase
trustworthiness and acceptability of smart systems in cars.
AB - OBJECTIVE: We examine whether trust in smart systems is generated analogously to
trust in humans and whether the automation level of smart systems affects
trustworthiness and acceptability of those systems. BACKGROUND: Trust is an
important factor when considering acceptability of automation technology. As
shared goals lead to social trust, and intelligent machines tend to be treated
like humans, the authors expected that shared driving goals would also lead to
increased trustworthiness and acceptability of adaptive cruise control (ACC)
systems. METHOD: In an experiment, participants (N = 57) were presented with
descriptions of three ACCs with different automation levels that were described
as systems that either shared their driving goals or did not. Trustworthiness and
acceptability of all the ACCs were measured. RESULTS: ACCs sharing the driving
goals of the user were more trustworthy and acceptable than were ACCs not sharing
the driving goals of the user. Furthermore, ACCs that took over driving tasks
while providing information were more trustworthy and acceptable than were ACCs
that took over driving tasks without providing information. Trustworthiness
mediated the effects of both driving goals and automation level on acceptability
of ACCs. CONCLUSION: As when trusting other humans, trusting smart systems
depends on those systems sharing the user's goals. Furthermore, based on their
description, smart systems that take over tasks are judged more trustworthy and
acceptable when they also provide information. APPLICATION: For optimal
acceptability of smart systems, goals of the user should be shared by the smart
systems, and smart systems should provide information to their user.
PMID- 23156625
TI - Cusp catastrophe models for cognitive workload and fatigue in a verbally cued
pictorial memory task.
AB - OBJECTIVE: The aim of this study was to evaluate two cusp catastrophe models for
cognitive workload and fatigue. They share similar cubic polynomial structures
but derive from different underlying processes and contain variables that
contribute to flexibility with respect to load and the ability to compensate for
fatigue. BACKGROUND: Cognitive workload and fatigue both have a negative impact
on performance and have been difficult to separate. Extended time on task can
produce fatigue, but it can also produce a positive effect from learning or
automaticity. METHOD: In this two-part experiment, 129 undergraduates performed
tasks involving spelling, arithmetic, memory, and visual search. RESULTS: The
fatigue cusp for the central memory task was supported with the quantity of work
performed and performance on an episodic memory task acting as the control
parameters. There was a strong linear effect, however. The load manipulations for
the central task were competition with another participant for rewards, incentive
conditions, and time pressure. Results supported the workload cusp in which trait
anxiety and the incentive manipulation acted as the control parameters.
CONCLUSION: The cusps are generally better than linear models for analyzing
workload and fatigue phenomena; practice effects can override fatigue. Future
research should investigate multitasking and task sequencing issues, physical
cognitive task combinations, and a broader range of variables that contribute to
flexibility with respect to load or compensate for fatigue. APPLICATIONS: The new
experimental medium and analytic strategy can be generalized to virtually any
real-world cognitively demanding tasks. The particular results are generalizable
to tasks involving visual search.
PMID- 23156626
TI - The impact of intonation and valence on objective and subjective attention
capture by auditory alarms.
AB - OBJECTIVE: The objective was to study the involuntary capture of attention by
spoken words varying in intonation and valence. BACKGROUND: In studies of verbal
alarms, the propensity of alarms to capture attention has been primarily assessed
with the use of subjective ratings of their perceived urgency. Past studies
suggest that such ratings vary with the alarms' spoken urgency and content.
METHOD: We measured attention capture by spoken words varying in valence
(negative vs. neutral) and intonation (urgently vs. nonurgently spoken) through
subjective ratings and behavioral measures. The key behavioral measure was the
response latency to visual stimuli in the presence of spoken words breaking away
from the periodical repetition of a tone. RESULTS: The results showed that all
words captured attention relative to a baseline standard tone but that this
effect was partly counteracted by a relative speeding of responses for urgently
compared with nonurgently spoken words. Word valence did not affect behavioral
performance. Rating data showed that both intonation and valence increased
significantly perceived urgency and attention grabbing without any interaction.
CONCLUSION: The data suggest a congruency between subjective ratings and
behavioral performance with respect to spoken intonation but not valence.
APPLICATION: This study demonstrates the usefulness and feasibility of objective
measures of attention capture to help design efficient alarm systems.
PMID- 23156627
TI - The effect of SPAM administration during a dynamic simulation.
AB - OBJECTIVE: The objective of this study was to determine whether administration of
the situation present assessment method (SPAM) affects workload and/or task
performance. BACKGROUND: SPAM probes are thought to isolate workload from the
assessment of situation awareness (SA) by including a warning signal before
asking an SA-related question. However, there is a good reason to think that SPAM
may still have an effect on dynamic workload and task performance. Specifically,
nearly all dual tasks affect workload and performance; thus, it would be
surprising if SPAM did not. METHOD: Following the methods of Durso, Bleckley, and
Dattel, I evaluated workload and performance on the Air Traffic Scenarios Test in
SPAM, non-SPAM probe, and no-probe conditions. RESULTS: Global workload was
unaffected by probe administration. However, at least with novice performers,
SPAM probes affected task performance. CONCLUSION: The use of a warning signal
does not eliminate performance decrements associated with secondary tasks.
Moreover, there may be performance decrements unique to SPAM. APPLICATION:
Cautious users of online assessment measures, such as SPAM, may want to remove
performance immediately subsequent to probes from analysis, use an interprobe
interval longer than 2.83 min, and construct their assessment measures to reduce
display search times unrelated to primary task performance.
PMID- 23156628
TI - U.S. truck driver anthropometric study and multivariate anthropometric models for
cab designs.
AB - OBJECTIVE: This study presents data from a large-scale anthropometric study of
U.S. truck drivers and the multivariate anthropometric models developed for the
design of next-generation truck cabs. BACKGROUND: Up-to-date anthropometric
information of the U.S. truck driver population is needed for the design of safe
and ergonomically efficient truck cabs. METHOD: We collected 35 anthropometric
dimensions for 1,950 truck drivers (1,779 males and 171 females) across the
continental United States using a sampling plan designed to capture the
appropriate ethnic, gender, and age distributions of the truck driver population.
RESULTS: Truck drivers are heavier than the U.S.general population, with a
difference in mean body weight of 13.5 kg for males and 15.4 kg for females. They
are also different in physique from the U.S. general population. In addition, the
current truck drivers are heavier and different in physique compared to their
counterparts of 25 to 30 years ago. CONCLUSION: The data obtained in this study
provide more accurate anthropometric information for cab designs than do the
current U.S. general population data or truck driver data collected 25 to 30
years ago. Multivariate anthropometric models, spanning 95% of the current truck
driver population on the basis of a set of 12 anthropometric measurements, have
been developed to facilitate future cab designs. APPLICATION: The up-to-date
truck driver anthropometric data and multivariate anthropometric models will
benefit the design of future truck cabs which, in turn, will help promote the
safety and health of the U.S. truck drivers.
PMID- 23156629
TI - Aesthetics: Honoring the team approach.
PMID- 23156630
TI - The impact of effective online marketing.
PMID- 23156631
TI - Predictable stabilization of the lower denture: comment and reply.
PMID- 23156632
TI - Xerostomia: etiology, diagnosis, and management.
PMID- 23156633
TI - Exploring minimally invasive options: managing demands, expectations, and
outcomes.
PMID- 23156634
TI - A simple and effective treatment for white spots.
PMID- 23156635
TI - The new age of ethical cosmetic dentistry: implementing the concept of
progressive smile design.
PMID- 23156636
TI - How do masters do it?
PMID- 23156637
TI - The CT/CBCT-based team approach to care: Part 2: communication with the surgeon
to support the final prosthesis.
PMID- 23156638
TI - Place and restore dental implants economically.
PMID- 23156639
TI - Direct composite resins continue to evolve.
PMID- 23156640
TI - Utilizing bioactive liners. Stimulating post-traumatic dentin formation.
PMID- 23156641
TI - Flexible partial denture variations. The use of circumferential, combination, and
continuous clasp designs.
AB - The new design potential of the flexible partial and its clasp allows for a new
treatment approach to the well-established problems of retention, stability, and
strength. The 4 main clasp designs include the conventional, the circumferential,
the combination, and the continuous clasp. The proper use of these various
designs can be a strong foundation upon which to develop the clinical strengths
of the flexible partial denture.
PMID- 23156642
TI - Repair technique for broken cast teeth.
PMID- 23156643
TI - Misplaced hope: misleading health service practitioner representations and
consumer protection.
AB - A series of court and tribunal decisions in the course of 2012 in Australia has
highlighted the vulnerability of seriously ill patients to overtures and
advertising by charismatic health practitioners offering panaceas of unproven
efficacy. Drawing upon the findings of the Victorian Court of Appeal in relation
to Noel Campbell, the Deputy State Coroner of Western Australia in relation to
Helfried Sartori, and the Victorian Civil and Administrative Tribunal in relation
to Reza Ghaffurian, it is argued that there is a strong public interest in the
capacity for effective early intervention by government in relation to
unscrupulous and unethical conduct by health practitioners, whether they are
registered or unregistered. For Australia a constructive reform would be
nationally consistent legislation to regulate unregistered health practitioners.
PMID- 23156644
TI - Legal capacity under the Convention on the Rights of Persons with Disabilities.
AB - Article 12 of the United Nations Convention on the Rights of Persons with
Disabilities requires states parties to ensure that persons with disabilities
"enjoy legal capacity on an equal basis with others in all aspects of life". This
column explores what is meant by "legal capacity" and its constituent elements of
legal standing and legal agency. It outlines recent research on what is meant by
"support" to exercise legal capacity and explores the issue of whether mental
health and guardianship laws that enable substituted decision-making for those
with mental and intellectual impairments contravene Article 12.
PMID- 23156645
TI - A new ball game: the United Nations Convention on the Rights of Persons with
Disabilities and assumptions in care for people with dementia.
AB - The United Nations Convention on the Rights of Persons with Disabilities is a
powerful international instrument which imposes significant responsibilities on
signatories. This column discusses changes in the definition of legal capacity
which will have significant impacts on decision-making related to people with
dementia. Various restrictions and limitations on personal freedoms are discussed
in light of the Convention. The main focus is on challenges to existing paradigms
of substitute decision-making, which are in wide use through a guardianship
model. Under Art 12 of the Convention, moves to supported decision-making will
result in significant changes in ensuring the rights of people with dementia.
There are challenges ahead in implementing supported decision-making schemes, not
only due to tension with existing practices and legislation, but also the
difficulty of developing and resourcing workable schemes. This is particularly so
with advanced dementia, which is acknowledged as a pressing issue for Australia
due to effective health care, an ageing population and changing expectations.
PMID- 23156646
TI - A fair dinkum duty of open disclosure following medical error.
AB - Supporting patients and families in circumstances where medical error has caused
significant harm is said to be governed by the principles of ordinary treatment:
honest, open communication, empathy and respect. By and large, harmed patients
look for acknowledgment of the events that occurred including errors, acceptance
of responsibility, a sincere apology, and assurance that lessons learned will be
put to preventive use. Australia's National Open Disclosure Standard purports to
respond to these reasonable expectations, yet it advises health care
professionals that while they may express regret for what has occurred, they
should take care not to state or agree that they, or other health care
professionals, or health care organisations, are liable for the harm caused to
the patient. The National Open Disclosure Standard is currently being reviewed,
and the Consultation Draft of the Australian Open Disclosure Framework appears to
move things closer to its stated finding that ethical practice prioritises
organisational and individual learning from error, rather than an organisational
risk-management approach. However, it remains the case that the sense of apology
in the Consultation Draft is one of stating regret, not of accepting
responsibility This dissonance in the Draft Framework wording may represent a
continuing disingenuousness on the part of health professionals and their
institutions regarding the kind of apologies that patients look for. Following
Berlinger, the current author argues that expressions of regret are not
apologies, since an apology presupposes the fault that health professionals are
advised they avoid admitting. But honest, open communication surely implies both
materially relevant disclosure, which would include acknowledgment of fault where
that is known, and a genuine apology, as part of the continuing doctor-patient
relationship. To the extent that open disclosure policies and practices fudge
complete disclosure, admission of fault and genuine apology, they remain
deficient instruments in the respect and beneficence owed patients harmed by
health care. Advice to health care professionals to not admit fault, and
implicitly to not apologise genuinely, are motivated by legal liability
considerations. There is strong evidence that comprehensive communication,
including genuine apology and consistent with the medical ethical principle of
veracity, is associated with reduced levels of litigation. State health
department Open Disclosure policies and State and Territory civil liability
legislation should be reviewed to remove obfuscatory and dissembling language and
increase consistency between jurisdictions and between policies and statutes. The
National Open Disclosure Standard should be revised to encourage and support full
disclosure and genuine apology. If these processes fail, statutory reform should
be considered.
PMID- 23156647
TI - Civil liberties and the critics of safe vaccination: Australian Vaccination
Network Inc v Health Care Complaints Commission [2012] NSWSC 110.
AB - Public immunisation programs have, time and again, demonstrated their
effectiveness at reducing mortality and morbidity from vaccine-preventable
diseases such as measles and pertussis. Governments, health agencies and almost
all health practitioners regard vaccines as safe and cost-effective treatments
with a low risk profile. Nevertheless, despite, or perhaps because of, their
success, immunisation programs and vaccines have increasingly been questioned by
various lobby groups, sceptical of the safety of vaccines and the motives of
those who administer them. Whereas the reach of these groups would have once been
limited by the cost of postage, the internet has delivered a global audience. The
extent to which these anti-vaccination advocates are expected to comply with the
ethical and professional standards applied to registered health professionals
remains unresolved in Australia. As demonstrated in the case of Australian
Vaccination Network Inc v Health Care Complaints Commission [2012] NSWSC 110, the
ability of professional oversight bodies to regulate the information promoted by
these lobby groups is limited by traditional conceptions of the doctor-patient
relationship and the clinical setting in which medical advice is delivered.
Acknowledging that vaccines, like all medical treatments, involve some level of
risk, this article explores the relationship between the state, parents, family,
medical professionals and such lobbyists within a human rights framework,
suggesting that most public immunisation programs deliver benefits in "the best
interest of the child" that, on balance, provide a good result for the civil
liberties of Australians.
PMID- 23156648
TI - Levelling the playing field? Sharing of influenza viruses and access to vaccines
and other benefits.
AB - With the adoption of the Pandemic Influenza Preparedness Framework, including its
annexes, by the 64th World Health Assembly, this article investigates the
disproportionate burden of risk and benefits between resource-poor countries in
the developing South and resource-rich industrialised developed nations of the
North in the World Health Organisation's Standard Material Transfer Agreement
(SMTA) for accessing and sharing influenza viruses. It concludes that the
countries of the South have a unique opportunity to level the playing field
through providing timely and affordable access to life-saving vaccine and
meaningful benefit-sharing that will deliver technology and economic development.
Importantly, the article also demonstrates that SMTAs are not merely a
redirection of existing resources from North to South but offer a solution to the
ongoing shortage of pandemic influenza vaccine by enabling the South to access
technology necessary for sustainable vaccine production and thus increasing
global vaccine capacity.
PMID- 23156649
TI - The dollars and sense of restraints and seclusion.
AB - Restraints and seclusion are a common practice in many human service settings
despite the increasing evidence questioning their efficacy and appropriateness.
There are many detrimental effects on people subject to these practices, such as
falls, injury, psychological trauma and even death. In addition to the impact on
people being served, there is also a range of negative effects on organisations
and the workforce. This article outlines and discusses the costs to organisations
in implementing restraints and seclusion, and the economic cost-benefits to be
gained in working towards the safe elimination of restraints and seclusion. A
brief outline of ethical alternatives to restraints and seclusion is explored.
The emerging research evidence suggests that it is possible to achieve the safe
elimination of restraints and seclusion in a human service organisation.
PMID- 23156650
TI - Are people who claim compensation "cured by a verdict"? A longitudinal study of
health outcomes after whiplash.
AB - This study examines whether the lure of injury compensation prompts whiplash
claimants to overstate their symptoms. Claim settlement is the intervention of
interest, as it represents the point at which there is no further incentive to
exaggerate symptoms, and neck pain at 24 months is the outcome of interest.
Longitudinal data on neck pain scores and timing of claim settlement were
regressed, controlling for the effect of time on recovery, to compare outcomes in
claimants who had and had not settled their compensation claims. The results show
clearly that removing the financial incentive to over-report symptoms has no
effect on self-reported neck pain in a fault-based compensation scheme, and this
finding concurs with other studies on this topic. Policy decisions to limit
compensation in the belief that claimants systematically misrepresent their
health status are not supported empirically Claimants do not appear to be "cured
by a verdict".
PMID- 23156651
TI - Criticisms of African trials fail to withstand scrutiny: male circumcision does
prevent HIV infection.
AB - A recent article in the JLM (Boyle GJ and Hill G, "Sub-Saharan African Randomised
Clinical Trials into Male Circumcision and HIV Transmission: Methodological,
Ethical and Legal Concerns" (2011) 19 JLM 316) criticises the large randomised
controlled trials (RCTs) that scientists, clinicians and policy-makers worldwide
have concluded provide compelling evidence in support of voluntary medical male
circumcision (VMMC) as an effective HIV prevention strategy. The present article
addresses the claims advanced by Boyle and Hill, demonstrating their reliance on
outmoded evidence, outlier studies, and flawed statistical analyses. In the
current authors' view, their claims portray misunderstandings of the design,
execution and interpretation of findings from RCTs in general and of the
epidemiology of HIV transmission in sub-Saharan Africa in particular. At the same
time they ignore systematic reviews and meta-analyses using all available data
arising from good-quality research studies, including RCTs. Denial of the
evidence supporting lack of male circumcision as a major determinant of HIV
epidemic patterns in sub-Saharan Africa is unsubstantiated and risks undermining
the evidence-based, large-scale roll-out of VMMC for HIV prevention currently
underway. The present article highlights the quality, consistency and robustness
of the scientific evidence that underpins the public health recommendations,
guidance, and tools on VMMC. Millions of HIV infections will be averted in the
coming decades as VMMC services scale-up to meet demand, providing direct
benefits for heterosexual men and indirect benefits for their female partners.
PMID- 23156652
TI - Childhood obesity, parental duties of care and strategies for intervention.
AB - Childhood obesity is an increasingly serious issue which causes significant
health problems among children. There are numerous causes of childhood obesity.
However, the ultimate responsibility for the problems and costs associated with
an obese child should be attributed to that child's parents. Parents owe a duty
of care to their child and, when their child is obese, have arguably breached
that duty. However, if parents were required to pay their child damages, this
would arguably be problematic and of little utility. Rather, intervention
strategies should be implemented which seek to treat and prevent childhood
obesity and to address the identified causes of childhood obesity.
PMID- 23156653
TI - Reappraising consent: conducting ethical psychiatric research in Singapore.
AB - Singapore is legally restrictive when it comes to research involving minors. The
age of majority is 21 and parental consent is required for participation in
medical research. This article explores the age of majority and the issues
related to obtaining consent for research in Singapore, focusing on "young
adults" (17-21 years), using an example of a translational and clinical research
project called the Longitudinal Youth at Risk Study (LYRIKS). It describes the
unique legal and social conditions pertaining to the age of majority in
Singapore, before presenting an argument for consideration as to whether the age
of consent to participate in research should be reviewed. It concludes that
rather than a set of doctrinaire rules for the age of participation in research,
there should be an assessment of the kind of tasks that minors can assume
themselves in respect to a specific project, and the degree of parental
involvement.
PMID- 23156654
TI - The regulation of preimplantation genetic diagnosis: is there anything the United
Kingdom can learn from the Australian experience?
AB - The United Kingdom fertility regulator, the Human Fertilisation and Embryology
Authority (HFEA), is set to be abolished and its functions transferred to the
Care Quality Commission. Together with the Human Fertilisation and Embryology Act
1990 (UK), the HFEA has played a central role in the regulation of
preimplantation genetic diagnosis (PGD) and human leukocyte antigen tissue typing
(HLA typing). Australia, on the other hand, does not have a national regulatory
body for assisted reproductive technologies, which are instead regulated by a
series of national guidelines, State legislation and State regulators. Using PGD
and HLA typing as a focal point, this article asks, is there anything the United
Kingdom can learn from Australia?
PMID- 23156655
TI - The legal status of the fetus in New South Wales.
AB - The issue of how to define the legal status of the fetus is complex. Three
clinical cases with fetal losses following motor vehicle accidents raise
important issues regarding the legal status of the unborn child. Legislation was
submitted to the New South Wales Parliament in the form of the Crimes Amendment
(Grievous Bodily Harm) Bill 2005 (NSW) but was subsequently repealed. Medical
technological advances make the viability of a fetus a shifting standard and
encourage the comparison between newborns and late-term fetuses, offer increased
fetal health status information and provide greater capacity to maintain the life
of babies born prematurely. In view of the sophisticated state of medical care
available in New South Wales, the three cases reviewed highlight the discrepancy
between the medical recognition of the fetus as a patient and its lack of legal
recognition.
PMID- 23156656
TI - Avoiding a fate worse than death: an argument for legalising voluntary physician
based euthanasia.
AB - The legalisation of voluntary physician-based euthanasia is currently the subject
of much political, social and ethical debate and there is evidence in Australia
of growing support for its implementation. In addressing many of the issues that
surround legalisation, the article looks at some overseas jurisdictions that have
legalised euthanasia to determine whether the social, political and ethical
concerns prominent in the Australian debate have proved problematic in other
jurisdictions. In addition, the article examines the report on the Dying with
Dignity Bill 2009 (Tas) which commented extensively on the issues relating to
voluntary physician-based euthanasia.
PMID- 23156657
TI - The many cases of XFJ: suitable to drive a taxi or "killer cabbie"?
AB - For 10 years, the refugee now known by the pseudonym XFJ attempted to gain
accreditation to drive a taxi-cab. After many internal reviews and rejections by
the Victorian Taxi Directorate, XFJ appealed to the Victorian Civil and
Administrative Tribunal (VCAT). The difficulty for XFJ was that shortly after
arriving in Australia, he had killed his estranged wife. The Supreme Court of
Victoria subsequently found him not guilty of murder on the grounds of insanity.
Since XFJ's mental health has been stable for many years, much of the legal
argument at VCAT and the court cases that followed centred around whether he was
"suitable in other respects to provide the service" of driving a taxi, as
required by s 169(1)(b)(ii) of the Transport Act 1983 (Vic). This article looks
at the tension between the expert medical evidence and the concept of "suitable
in other respects" which XFJ's opponents claimed included the maintenance of
public confidence and the meeting of community expectations.
PMID- 23156658
TI - The economics of medical technology.
PMID- 23156659
TI - Aspects of research and development contract terms in the bio/pharmaceutical
sector.
AB - PURPOSE: The cost of new drug development is increasing every year.
Pharmaceutical companies use R&D joint ventures, mergers, and outsource different
stages of pharmaceutical R&D activities for a faster and cost minimizing method
of innovation. Pharmaceutical companies outsource R&D activities to independent
small biotech or pharmaceutical companies that specialize in different stages of
pharmaceutical R&D. This chapter examines the determinants of the payment
structure of research contracts between large bio/pharmaceutical companies and
specialized research firms. METHODS: Determinants of R&D contracts are analyzed
using detailed R&D contract data between bio/pharmaceutical companies and
independent research firms for 10 years. A multinomial logit model is used in
order to understand the determinants of three different types of contracts;
royalty contracts, fixed payment contracts, and the mixed contracts. FINDINGS:
Under uncertainty, the likelihood of a royalty contract rises for the early
stages of the research and with the patent stock of the research firm. It is more
likely to observe both royalty and fixed payment if the pharmaceutical client has
past contracts with the same research firm. The results also suggest that if Food
and Drug Administration (FDA) is more stringent in any disease area in reviewing
the new drug application, then the likelihood of signing pure royalty contract
decreases. IMPLICATIONS: Understanding the nature of R&D contracts and the
effects of FDA's behavior on the pharmaceutical R&D contract is important because
these contracts not only affect the cost of new drug invention but also the
quality and the rate of invention. VALUE: Results are useful for both the
pharmaceutical companies and the economic/business researchers.
PMID- 23156660
TI - Effects of regulation on drug launch and pricing in interdependent markets.
AB - PURPOSE: This study examines the effect of price regulation and competition on
launch timing and pricing of new drugs. METHODS: Our data cover launch experience
in 15 countries from 1992 to 2003 for drugs in 12 major therapeutic classes. We
estimate a two-equation model of launch hazard and launch price of new drugs.
FINDINGS: We find that launch timing and prices of new drugs are related to a
country's average prices of established products in a class. Thus to the extent
that price regulation reduces price levels, such regulation directly contributes
to launch delay in the regulating country. Regulation by external referencing,
whereby high-price countries reference low-price countries, also has indirect or
spillover effects, contributing to launch delay and higher launch prices in low
price referenced countries. IMPLICATIONS: Referencing policies adopted in high
price countries indirectly impose welfare loss on low-price countries. These
findings have implications for US proposals to constrain pharmaceutical prices
through external referencing and drug importation.
PMID- 23156661
TI - The effect of pharmaceutical innovation on the functional limitations of elderly
americans: evidence from the 2004 National Nursing Home Survey.
AB - PURPOSE: To examine the effect of pharmaceutical innovation on the functional
status of nursing home residents. METHODOLOGY/APPROACH: Estimation of econometric
models of the ability of nursing home residents to perform activities of daily
living (ADLs) using cross-sectional, patient-level data from the 2004 National
Nursing Home Survey. The explanatory variables of primary interest are the
characteristics (e.g., the mean vintage (FDA approval year)) of the medications
used by the resident. We control for age, sex, race, marital status, veteran
status, where the resident lived prior to admission, primary diagnosis at the
time of admission, up to 16 diagnoses at the time of the interview, sources of
payment, and facility fixed effects. FINDINGS: The ability of nursing home
residents to perform ADLs is positively related to the number of "new" (post
1990) medications they consume, but unrelated to the number of old medications
they consume. I estimate that if 2004 nursing home residents had used only old
medications, the fraction of residents with all five ADL dependencies (number of
activities for which the resident is not independent) would have been 58% instead
of 50%. SOCIAL IMPLICATIONS: During 1990-2004, pharmaceutical innovation for
reduced the functional limitations of nursing home residents by between and 1.2%
and 2.1% per year. ORIGINALITY/VALUE OF CHAPTER: The first public-use survey of
nursing homes that contains detailed information about medication use, and better
data on functional status than previous surveys, is used to help explain why
there has been a significant decline in the functional limitations of older
people.
PMID- 23156662
TI - Comparative effectiveness research, technological abandonment, and health care
spending.
AB - PURPOSE: Policymakers hope that comparative effectiveness research will identify
examples of widely used therapies that are no better than less expensive
alternatives and, consequently, reduce health care spending. Comparative
effectiveness research is unlikely to reduce spending if physicians are quick to
adopt effective treatments but slow to abandon ineffective ones.
METHODOLOGY/APPROACH: We present a theoretical model that shows how physicians
will adopt new treatments in response to positive evidence more readily than they
abandon existing treatments in response to negative evidence if the marginal
costs of production decline post-adoption. We report trends in the use of two
common procedures, percutaneous coronary intervention (PCI) for patients with
stable angina and routine episiotomy in vaginal childbirth, where comparative
effectiveness research studies have failed to find evidence of a benefit.
FINDINGS: Use of PCI and episiotomy have declined over time but are still
excessive based on the standards implied by comparative effectiveness research.
PRACTICAL IMPLICATIONS (IF APPLICABLE): The findings suggest that comparative
effectiveness research has the potential to reduce costs but additional efforts
are necessary to fully realize savings from abandonment. ORIGINALITY/VALUE OF
CHAPTER: There is a large literature on technological adoption in health care,
but few studies address technological abandonment. Understanding abandonment is
important for efforts to decrease health care costs by reducing use of
ineffective but costly treatments.
PMID- 23156663
TI - How do initial signals of quality influence the diffusion of new medical
products? The case of new cancer drug treatments.
AB - PURPOSE: Objective measures of a new treatment's expected ability to improve
patients' health are presumed to be significant factors influencing physicians'
treatment decisions. Physicians' behavior may also be influenced by their
patients' disease severity and insurance reimbursement policies, firm promotional
activities and public media reports. This chapter examines how objective evidence
of the incremental effectiveness of novel drugs to treat cancer
("chemotherapies") impacts the rate at which physicians' adopt these treatments
into practice, holding constant other factors. DESIGN/METHODOLOGY: The novelty of
the analysis resides in the dataset and estimation strategy employed. Data is
derived from a United States population-based chemotherapy order entry system,
IntrinsiQ Intellidose. Quality/price endogeneity is overcome by employing sample
selection methods and an estimation strategy that exploits quality variation at
the molecule-indication level. Pooled diffusion rates across molecule-indication
pairs are estimated using nonparametric hazard models. FINDINGS: Results suggest
incremental effectiveness is negatively and nonsignificantly associated with the
diffusion of new chemotherapies; faster rates of diffusion are positively and
significantly related to low five-year survival probabilities and measures of
perceived clinical significance. Results are robust to numerous specification
checks, including a measure of alternative therapeutic availability. We discuss
the magnitude and potential direction of bias introduced by several threats to
internal validity. Evidence of incremental effectiveness does not appear to
motivate the rate of specialty physician diffusion of new medical treatment; in
all models high risk of disease mortality and perceptions of therapeutic quality
are significant drivers of physician use of novel chemotherapies.
VALUE/ORIGINALITY: Understanding the rate of technological advance across
different clinical settings, as well as the product-, provider-, and patient
level determinants of this rate, is an important subject for future research.
PMID- 23156664
TI - Technology diffusion and substitution of medical innovations.
AB - PURPOSE: The aim of this paper is to examine the diffusion of a new surgical
procedure with lower per-case cost and how its diffusion path is affected by the
simultaneous introduction of a new drug class that may be an effective treatment
to prevent surgery. In particular, we examine whether a process of technology
substitution exists that influences the diffusion process of the surgical
technology. Given their different cost implications, the interaction of these two
different technologies, surgery and drug intervention, is relevant from the
perspective of health expenditure. This is of particular interest in health care
as technology adoption and diffusion has been cited as a major driver of
expenditure growth. Such expenditure growth has been increasingly targeted
through the use of market-orientated policy tools aimed at increasing efficiency.
Our research is thus addressing the question of how economic incentives influence
the diffusion process and we discuss the impact of a set of incentives on
hospital behavior. DESIGN/METHODOLOGY: Hospital admission data for the financial
years 1998/1999 to 2007/2008 in England are used to empirically test the
contribution of prescription uptake and market-oriented reforms. Dynamic panel
data models are used to capture any changes in technology preference during the
period of study. FINDINGS: Our results suggest that the hospital sector exhibits
a strong new technology preference, tempered by the interaction of competition
for patients and the ability of the primary care sector to substitute treatments.
VALUE/ORIGINALITY: Given the current fast technological change, we examine the
technological race occurring in the health care sector. We account simultaneously
for the diffusion of different technologies not only within the same typology but
also with technologies of a different class.
PMID- 23156665
TI - Health insurance and hospital technology adoption.
AB - PURPOSE: This chapter discusses the relationship between health insurance and
hospitals' decisions to adopt medical technologies. I focus on both how the
extent of insurance coverage can increase incentives to adopt new treatments, and
how the parameters of the insurance contract can impact the types of treatments
adopted. METHODOLOGY/APPROACH: I provide a review of the previous theoretical and
empirical literature and highlight evidence on this relationship from previous
expansions of Medicaid eligibility to low-income pregnant women. FINDINGS: While
health insurance has important effects on individual-level choices of health care
consumption, increases in the fraction of the population covered by insurance has
also been found to have broader supply side effects as hospitals respond to
changes in demand by changing the type of care offered. Furthermore, hospitals
respond to the design of insurance contracts and adopt more or less cost
effective technologies depending on the incentive system. RESEARCH
LIMITATIONS/IMPLICATIONS: Understanding how insurance changes supply side
incentives is important as we consider future changes in the insurance landscape.
ORIGINALITY/VALUE OF PAPER: With these previous findings in mind, I conclude with
a discussion of how the Affordable Care Act may alter hospital technology
adoption incentives by both expanding coverage and changing payment schemes.
PMID- 23156666
TI - Reframe the health debate.
PMID- 23156667
TI - What to do when the crisis hits.
PMID- 23156668
TI - [The chicken beta-globin genes: a model system for studying transcription
regulation at the level of genomic domains].
AB - In the last quarter of the XX century, as a result of studies performed on a
number of model systems, a hypothesis was formulated according to which the
genome of higher eukaryotes consists of functionally isolated areas named genomic
domains. Each domain includes one or more genes and a regulatory system that is
normally active only in respect of this domain and allows it to achieve the
regulatory autonomy of the neighboring chromosome regions. A genomic domain is
characterized by the spectra of covalent histone modifications which define the
boundaries of the domain and the degree of chromatin condensation within it, and
so, the probability of transcription activation of genes within the domain.
Development of the domain hypothesis of genome organization became possible to a
large extent through the study of mechanisms of transcriptional regulation of the
globin genes in vertebrates. One of the most popular models in this field of
molecular biology is the chicken beta-globin gene domain. Based on this model
system, the fundamental principles of complex enhancer action in higher
eukaryotes have been described, the properties of insulators and functional units
of enhancers and promoters have been studied, the influence of covalent histone
modifications on the level of chromatin condensation and their role in the
regulation of transcription within the domain have been investigated. In this
review we summarize the data on the study of the chicken beta-globin gene domain,
as well as consider the domain hypothesis of eukaryotic genome organization.
PMID- 23156669
TI - [Protein complementation as tool for studying protein-protein interactions in
living cells].
AB - Association and degradation of protein complexes play essential role in a
majority of normal and pathologic processes, which take place in living cell.
Studying the underlying mechanisms of those interactions would give deeper
understanding of specific causes of disease progression and would allow
developing new therapeutic strategies. The majority of technical approaches
currently used for detecting protein association include in vitro protein
extraction and purification, whereas more relevant results require methods that
can be used in vivo. One of a few approaches for in vivo protein association
detection is based on reporter protein fragment complementation. Reporter systems
based on protein complementation rely on reconstitution of reporter protein
fluorescent or enzymatic activity which occurs upon reassociation of protein
fragments and could be measured by colorimetry, luminometry or fluorimetry.
Protein complementation is widely used to develop reporter systems for analysis
of protein interactions, for functional dissection of signal transduction
pathways and for performing high-throughput screenings to discover new protein
interaction partners. Currently developed approaches that utilize protein
fragment complementation have possibilities that extend far beyond simple
detection of interaction in a pair of proteins.
PMID- 23156670
TI - [Oncolytic enteroviruses].
AB - Increasing information concerning molecular biology of viruses and virus-cell
interactions makes it possible to use viruses as a tool in effort to treat cancer
diseases. As a rule, tumor cells are highly sensitive to viruses that may be used
in cancer therapy. Therewith, applications of viral oncolysis in treatment of
cancer diseases assume maximum possible safety of used viruses for patient and
environment. Human enteroviruses are one of the most convenient sources to
generate oncolytic viruses. Many of enteroviruses are non-pathogenic for humans
or cause mild disease. Progress in genetic engineering permits to develop
attenuated enterovirus variants with high safety and selectivity. This review
focuses on the main members of Enterovirus genus, such as Coxsackieviruses, and
vaccine strains as promising source for development of oncolytic agents,
applicable for cancer therapy. It reviews data concerning recently developed and
tested oncolytic variants of enteroviruses and discusses perspectives of their
application in cancer therapy and problems, concerning their improvement and
practical use.
PMID- 23156671
TI - [Recombinational repair in Schizosaccharomyces pombe: the role of mediator
proteins].
AB - Repair of double-stranded DNA breaks that occur spontaneously or under the
influence of external factors, are critical for cell survival. Evolutionarily
conserved mechanism for error-free recombinational repair plays a major role in
maintaining genome integrity. Repair pathway is conservative and has a number of
similarities in lower eukaryotes and vertebrates. This review examines the
current state of studying the mechanism of recombinational repair double-stranded
DNA breaks in the fission yeast Schizosaccharomyces pombe, notes the differences
of this type of repair in Saccharomyces cerevisiae and higher eukaryotes.
PMID- 23156672
TI - [Detection of nonsense and frame shift mutations in human BRCA1 gene using new
plasmid vector pPhoA-frame].
AB - The technique for the detection of frame shift and nonsense mutations in BRCA1
gene was suggested. The technique presumes the construction of recombinant
plasmids where the tested DNA fragment placed in-frame with alkaline phosphatase
gene of Escherichia coli (phoA). A plasmid pPhoA-frame was constructed for such
analysis, the plasmid contains DNA fragment coding for alkaline phosphatase of E.
coli. Synthetic DNA fragment with BglII, StuI, ApaI and SacII sites was inserted
into the DNA fragment coding for alkaline phosphatase of E. coli between Ala218
and Gly219 codons to facilitate the cloning of BRCA1 gene fragments. Occurrence
of the frame shift or nonsense mutation in the tested DNA fragment can be
detected after transformation of E. coli by the recombinant plasmid containing
the tested fragment. E. coli colonies with the newly constructed recombinant
plasmids are plated out on the indicator agar. In the case of frame shift or
nonsense mutation the colonies are not colored, DNA fragments without such
mutations result in the formation of the blue colonies.
PMID- 23156673
TI - N-acetylcysteine enhances neuronal differentiation of P19 embryonic stem cells
via Akt and N-cadherin activation.
AB - We examined whether N-acetylcysteine (NAC) enhanced embryonic body (EB) formation
and neuronal differentiation in terms of EB formation, neuronal marker
(microtubule-associated protein 2; MAP-2) expression, and neuron maturation using
P19 embryonic stem cells. The size and numbers of EBs were greatly increased,
together with the up-regulated N-cadherin expression. Also, MAP-2 expression and
neurite outgrowth were much increased with activation of serine/threonine protein
kinase (Akt) and blocked by addition of an Akt inhibitor (LY294002). Our results
suggested that NAC increased EB formation by up-regulating the N-cadherin
expression. Furthermore, NAC-enhanced neuronal differentiation was mediated by
activation of Akt.
PMID- 23156674
TI - [Fragment of mRNA coding part that is complementary to region 1638-1650 of wheat
18S rRNA functions as a translational enhancer].
AB - Possible involvement of 18S rRNA fragment 1638-1650 including basements of the
helices h44 and h28 and nucleotides of the ribosomal decoding site in the cap
independent translation initiation on plant ribosomes is studied. This rRNA
fragment is shown to be accessible for complementary interactions within the 40S
ribosomal subunit. It is found that the sequence complementary to the 18S rRNA
fragment 1638-1650 is able to enhance efficiency of a reporter mRNA translation
when placed just after the initiation codon. The results obtained indicate that
in the course of the cap-independent translation initiation, complementary
interactions can occur between mRNA coding sequence and 18S rRNA fragment in the
region of the ribosomal decoding site.
PMID- 23156675
TI - [Repressional effects of the glutamate antibodies on expression of Dffb gene in
the brain of rats with experimental Alzheimer's disease].
AB - The intranasal administration of glutamate antibodies in the dose of 300
microg/kg one hour after damage on the level of mRNA expression of Dffb gene
which codes caspase-activated DNase which participates in intranucleosome
fragmentation of genome DNA in apoptosis was investigated in experimental
Alzheimer's disease induced by injection of neurotoxic fragment of beta-amyloid
protein Abeta25-35 in Meynert basal magnocellular nuclei on rats. On the Day 3
after Abeta25-35 injection is observed significant decrease of the level of mRNA
expression of Dffb gene in prefrontal cortex in 37%, and in hippocampus in 62% in
the experiment group versus the control group. These differences were not found
in the hypothalamus when comparing the experimental and control animals. It was
suggested that repressive effect of glutamate antibodies on the level of mRNA
expression of Dffb gene reflects stabilization of processes taking place in brain
cells in experimental Alzheimer's disease, and in its turn the intensiveness of
nerve and glial cells apoptotic death is decreased.
PMID- 23156676
TI - [Early detection of cancer/testis mRNAs in tumor cells circulating in the
peripheral blood of colorectal cancer patients].
AB - Recent studies have suggested that mRNAs transcribed from cancer/testis genes
might be used as biomarkers of cancer cells migrating through the bloodstream.
Using RT-PCR we evaluated the expression of several cancer/testis mRNAs (MAGEA1
6, GAGE1-8, NY-ESO-1, SSX1, 2, and 4, XAGE1 and MAGEC1) in primary tumors and
peripheral blood samples of colorectal cancer patients. The detection rate of at
least one of the transcripts was 95% (37/39 samples) for primary tumors and 81%
(52/64 samples) for the peripheral blood. Moreover, selected mRNAs were
detectable in cellular fraction of the peripheral blood at all stages the disease
(14 out of 14 cases), whereas in extracellular fraction of plasma were found only
at stages III and IV. Obtained data open a possibility of early diagnosis of
colorectal cancer in people at high risk by peripheral blood analysis.
PMID- 23156677
TI - [Methylation of some miRNA genes is involved in the regulation of their target
genes RAR-beta2 and NKIRAS1 expression in lung cancer].
AB - To date, there are more than two thousand human miRNAs, each of them may be
involved in the regulation of hundreds of protein coding target genes.
Methylation of CpG-islands, in turn, affects miRNAs gene expression. Our aim was
to evaluate the role of methylation in the regulation of miRNA gene expression
and, consequently, in the regulation of expression of target genes in primary
lung tumors. Using a common collection of non-small cell lung cancer samples we
performed a comprehensive study, including analysis of the methylation status and
expression levels of some miRNA genes and their potential target genes on
chromosome 3: RAR-beta2 and NKIRAS1. Increased frequency of methylation in lung
tumors compared to histologically normal tissue was revealed for miR-9-1 and miR
34b/c genes with significant statistics (P < or = 0.05 by Fisher exact test) and
for miR-9-3 and miR-193a was marginally significant (P < or = 0.1). Significant
correlation was revealed between alterations of methylation and expression level
of miR-9-1 gene (P = 5 x 10(-12) by Spearman) in the lung tumors, this suggests
the role of methylation in the regulation of expression of this miRNA genes.
Besides, a statistically significant negative correlation (P = 3 x 10(-12)-5 x
10(-13) by Spearman) was found between alterations of expression levels of miR-9
1 and miR-17and RAR-beta2 target gene and also between expression level
alterations of miR-17 and NKIRAS1 that was not previously analyzed. The inverse
relationship between expression levels of miRNA genes and their target genes is
consistent with the known mechanism of suppression of protein coding genes
expression under the action of miRNAs. For the first time significant
correlations (P = 3 x 10(-10)-4 x 10(-13) by Spearman) were shown between
alterations of methylation status of miRNA genes (miR-9-1, miR-9-3, miR-34b/c,
miR-193a) and the expression level of RAR-beta2 target gene and between
alterations of methylation status of miR-34b/c, and miR-193a and the expression
level of NKIRAS1 target gene in the primary lung tumors, which suggests the
possibility of indirect effects of methylation of miRNA genes on expression level
of target genes.
PMID- 23156678
TI - [Heterogeneous expression of CD38 gene in tumor tissue in patients with
colorectal cancer].
AB - The CD38 gene codes a membrane protein which takes part in cell adhesion and
catalyzes the formation of cyclic ADP-ribose. Using RT-PCR method we tested the
presence of full-size and alternative forms of mRNA CD38 in samples of tumor
tissue of patients with colorectal cancer and in tumor cell lines. It was shown
that there are the cells in the tumor tissue which expressed CD38 gene. In tumor
tissue of patients the alternative form of mRNA CD38 was detected less frequently
than full-size form. Cells of lines Colo-205, T-84, HCT15 and HCT116 contained
mRNA CD38, in cells of lines Caco-2 and SW-620 mRNA CD38 was absent. In cells of
tumor tissue on the first stage of colorectal cancer CD38 gene was expressed in
100% of cases. On the second, third and fourth stages of the disease gene
expression was observed less often. The frequency of mRNA CD38 detection not
depend on tumor localization, tumor grade and presence of metastases. Using
method of restriction analysis CpG methylation was detected in binding sites of
transcription factor Sp1 and receptor of retinoic acid (RARE) in all tested
samples of tumor tissue independently of the presence or absence of mRNA CD38.
The obtained data suggest that in the tumor cells of patients with colorectal
cancer the expression of the CD38 gene is heterogeneous.
PMID- 23156679
TI - [Irregular activity oscillations of rotary molecular motor. A simple kinetic
model of F1-ATPase].
AB - F1-ATPase is a catalytic portion of the rotary molecular motor, F1Fo-ATP
synthase. Cooperative ATP hydrolysis at the three catalytic sites of the F1
ATPase is connected with rotation of the central gamma-subunit inside a cylinder
made of three a subunits and three beta subunits. Various experimental works have
shown that the gamma-subunit rotates with irregular dwells. A simple kinetic
model of this paper explains dwells during rotation as a result of the
deterministic chaos. It is shown that the deterministic chaos occurs under the
rate constants close to the known experimental estimations. Time duration of
dwells in the model are close to those observed experimentally. Our model
explains the known irregular occupancy of catalytic sites of F1-ATPase by
nucleotides.
PMID- 23156680
TI - [Protein families specific for plastoms in small taxonomy groups of algae and
protozoa].
AB - Protein clustering is useful for refinement of protein annotation as well as
cluster finding by its phylogenetic profile. We performed clustering of plastid
encoded proteins from Rhodophyta as well as other plastid containing species
related to Rhodophyta branch on species tree. Data base for cluster finding by
its phylogenetic profile is available on http://lab6.iitp.ru/ppc/redline. By
means of the database distinctive proteins for plastoms from small taxonomy
groups of algae and protozoa were found. We performed finding and analysis of RNA
polymerases encoded in Apicomplexa nuclei.
PMID- 23156681
TI - Universal primers for amplification of the complete mitochondrial control region
in marine fish species.
AB - Through multiple alignment analysis of mitochondrial tRNA-Thr and tRNA-Phe
sequences from 161 fishes, new universal primers specially targeting the entire
mitochondrial control region were designed. This new primer set successfully
amplified the expected PCR products from various kinds of marine fish species,
belonging to various families, and the amplified segments were confirmed to be
the control region by sequencing. These primers provide a useful tool to study
the control region diversity in economically important fish species, the possible
mechanism of control region evolution, and the functions of the conserved motifs
in the control region.
PMID- 23156682
TI - [Development of biochip for determination of Y-haplogroups occuring in Russian
populations].
AB - Biochip has been developed which allowed to determine the following Y-chromosome
haplogroups: C, DE, G, H, I, J, L, N, O, R in a DNA sample. The following SNPs
were choosen as haplogroup markers: M130, M145, P257, M69, U179, M304, M185,
M231, M175, P224, correspondingly. The genotyping included two-round PCR with
fluorescent label incorporation into PCR product followed by hybridization with
immobilized probes on biochip. The analysis of fluorescent signal ratios in pairs
of immobilized probes "wild-type probe"--"group specific probe" for each of
choosen polymorphic markers showed high accuracy of Y-haplogroup genotyping using
biochip. The reliability of genotyping was confirmed by direct sequencing.
PMID- 23156683
TI - [Co-localization of selenium-containing protein V (seIV) and its partners in
mammalian cells].
PMID- 23156684
TI - [Ultramicrobacteria: Formation of the concept and contribution of
ultramicrobacteria to biology].
PMID- 23156685
TI - [Changes in the species composition of a thermotolerant community of acidophilic
chemolithotrophic microorganisms upon switching to the oxidation of a new energy
substrate].
PMID- 23156686
TI - [Rates of sulfide mineral oxidation by acidophilic chemolithotrophic microbial
communities from various sources].
PMID- 23156687
TI - [Differences in the carbohydrate composition between the yeastlike and mycelial
cells of Mucor hiemalis].
PMID- 23156688
TI - [Characterization of the Pragia fontium Lipopolysaccharides].
PMID- 23156689
TI - Characterization of the novel xylanase from the thermophilic Geobacillus
thermodenitrificans JK1.
AB - Thermophilic strain JK1 was isolated from compost using xylan as a single carbon
source. On the basis of 16S rRNA gene phylogenetic analysis and spo0A gene
sequence similarity analysis, strain JK1 was identified as Geobacillus
thermodenitrificans strain. During the exponential culture growth, the strain JK1
was found to produce the single xylan degrading enzyme -45 kDa in size. Xylose
was not an inducer of this xylanase. Cloning, expression and characterization of
the recombinant xylanase were performed. Xylanase of G. thermodenitrificans JK1
was cellulase-free; pH and temperature optimums were found to be 6.0 and 70
degrees C, respectively. The metal ions Na+, K+, Ca2+, and Co2+ showed partial
inhibition of the activity, while Mn2+ had slight stimulating effect on the
enzymatic activity. Recombinant xylanase was thermostable over the temperature
range of 55-70 degrees C. It presented the highest stability after incubation at
55 degrees C for 60 min showing 84% residual activity. 50% residual activity was
revealed after incubation at 60 degrees C for 60 min as well as at 65 and 70
degrees C for 30 min. Results of the thermostability experiments showed xylanase
of JK1 having quite low thermostability when compared with the respective enzymes
of the other geobacilli.
PMID- 23156690
TI - [Cell wall teichoic acids of Bacillus licheniformis VKM B-511T, Bacillus pumilus
VKM B-508T, and other strains previously assigned to Bacillus pumilus].
PMID- 23156691
TI - [Reactivation of dormant and nonculturable bacterial forms from paleosoils and
subsoil permafrost].
PMID- 23156692
TI - [A novel filamentous planctomycete of the Isosphaera-Singulisphaera group
isolated from a Sphagnum peat bog].
PMID- 23156693
TI - [ Change in the temperature preferences of Beauveria bassiana sensu lato isolates
in the latitude gradient of Siberia and Kazakhstan].
PMID- 23156694
TI - [First report on bacteria of the family Spirochaetaceae from digestive tract of
endemic gastropods from Lake Baikal].
PMID- 23156695
TI - [Factors controlling the activity of the microbial community of the alkaline Lake
Beloe (Transbaikal Region)].
PMID- 23156696
TI - [Microbial decomposition of organic matter in the bottom sediments of small lakes
of the urban landscape (Lithuania)].
PMID- 23156697
TI - [Diversity of cultivable bacteria isolated from the water column and bottom
sediments of the Kara Sea shelf].
PMID- 23156698
TI - [Application of the inhibition of bacterial bioluminescence test for assessment
of toxicity of carbon-based nanomaterials].
PMID- 23156699
TI - A simple purification procedure of D-amino-acid oxidase from Candida
guilliermondii H(see symbol)-4.
AB - D-amino-acid oxidase (EC 1.4.3.3) was purified about 1480-fold from the yeast
Candida guilliermondii H(see symbol)-4 using chromatofocusing method. The
purification procedure gave an enzyme preparation which is greater than 90%
homogenous on SDS-polyacrylamide gels with a specific activity of 11.54 U/mg at
30 degrees C with D-proline as substrate with the yield of total activity 9.3%.
The molecular weights of subunit and native enzyme were determined to be 38.4 and
78.6 kDa by SDS-polyacrylamide gel electrophoresis and gel-filtration,
respectively, suggesting that the native enzyme exists as a homodimer. A single
molecular form with an isoelectric point of 6.85 was detected in analytical
isoelectrofocusing. The optimum pH and temperature were 8.0 and 33 degrees C. An
enzyme shows stability in the pH range from 7.4 to 9.0 and at the temperature no
higher than 38 degrees C. Activation energy for D-amino-acid oxidase reaction was
calculated to be 60 kJ/mol at 30 degrees C. The strict D-isomer specificity of
the enzyme is confirmed, since no reaction could be detected with L-amino acids,
and a large number of D-amino acids could be substrates for this enzyme. K(m) and
V(max) values were determined for D-proline and D-alanine, which, among 22
tested, were the best substrates of the enzyme. D-amino-acid oxidase from the
yeast C. guilliermondii is a flavoprotein oxidase in which the prosthetic group
is tightly, but not covalently, bound FAD. The enzyme is completely inhibited by
sodium benzoate, SH-oxidizing agents, but not by sodium azide, toluene or
chloroform.
PMID- 23156700
TI - [Green microalgae isolated from associations with white sea invertebrates].
PMID- 23156701
TI - Iron storage disorders in captive wild mammals: the comparative evidence.
AB - Excessive burden of iron, or iron storage disease (ISD), has been reported in a
large variety of captive mammal species, including browsing rhinoceroses; tapirs;
fruit bats; lemurs; marmosets and some other primates; sugar gliders; hyraxes;
some rodents and lagomorphs; dolphins; and some carnivores; including procyonids
and pinnipeds. This report collates the comparative evidence for species'
susceptibility, recognizing that the data for mammal species are limited.
Differences reported in the occurrence of ISD between facilities, or within
facilities over periods that span management changes, have been reported in
individual cases but are underused in ISD research. Given the species
composition, the hypothesis that evolutionary adaptations to the iron content and
availability in the natural diet determine a species' susceptibility to ISD (in
the face of deviating iron content and availability in diets offered in
captivity) seems plausible in many cases. But exceptions, and additional species
putatively susceptible based on this rationale, should be investigated. Whereas
screening for ISD should be routine in zoo animal necropsy, screening of live
individuals may be implemented for valuable species, to decide on therapeutic
measures such as chelator application or phlebotomy. Whatever the reasons for ISD
susceptibility, reducing dietary iron levels to maintenance requirements of the
species in question seems to be a logical, preventive measure.
PMID- 23156702
TI - Iron homeostasis and its disorders in mice and men: potential lessons for rhinos.
AB - During the last decade, there have been remarkable advances in the understanding
of iron homeostasis and its disorders. This review summarizes our presentation at
the International Workshop on Iron Storage Disease in Black Rhinos that was held
in Orlando, Florida, USA, from 23 to 26 February 2011, and it is directed to
veterinarians and nutritional experts who treat rhinoceroses. This review
summarizes the current knowledge in humans and mice regarding the physiology and
molecular basis of iron overload, and it explores how it can be applied to the
problem of iron overload in captive rhino populations.
PMID- 23156703
TI - Avian iron storage disease: variations on a common theme?
AB - Many frugivorous avian species kept in captivity develop iron storage disease
(ISD) as indicated by high concentrations of hepatic iron and hemosiderin
deposits in hepatocytes or phagocytes. In several susceptible species fed diets
containing moderate levels of iron, ISD develops because of an inability to match
rates of iron absorption to tissue needs. Evidence suggests that the
pathophysiologic basis of excess iron absorption is due to high levels of
expression of divalent metal transporter-1 that transports iron into enterocytes
in the proximal intestine, and ferroportin that exports iron to the circulation.
The regulatory basis for this inability to sufficiently down-regulate iron
absorption is unknown, but disruptions in the hepcidin-ferroportin axis are
likely candidates based on recent research in humans and laboratory rodents. It
is likely that ISD-susceptible avian species evolved on foods that were very low
in bioavailable iron, so there was strong selection pressure for the efficient
capture of the small amount of dietary iron but low selection pressure for
preventing iron toxicities. Thus, the transporters and regulatory networks for
iron absorption seem to be heavily skewed toward iron storage even when food
items that are high in iron are consumed. Infections, trauma and neoplasias that
trigger an acute phase response may exacerbate ISD in susceptible species and may
be the primary cause in species that are normally resistant to ISD (i.e., those
that are normally able to shut down intestinal iron absorption when iron stores
are replete). The evolutionary basis that resulted in some avian species to be
susceptible to ISD (e.g., dietary cause) seems to differ from many inherited ISD
disorders in humans that are thought to have evolved to bolster protection
against infectious diseases. However the evolutionary basis of ISD in other
mammalian species might be more similar to that in ISD-susceptible avian species.
PMID- 23156704
TI - Hemochromatosis and fatty liver disease: building evidence for insulin resistance
in bottlenose dolphins (Tursiops truncatus).
AB - Hemochromatosis in bottlenose dolphins (Tursiops truncatus) is associated with
high postprandial plasma insulin levels, suggestive of insulin resistance. In
humans, insulin resistance is associated with liver pathologies, including
excessive iron deposition and nonalcoholic fatty liver disease. Dolphin liver
tissues, in addition to excessive iron storage, were evaluated for other
pathologies supportive of underlying insulin resistance. Archived liver tissues
collected postmortem during 1985-2010 from 18 dolphins (median age 27.9 yr, range
0.7-51.4) that were part of the Navy Marine Mammal Program's managed collection
were assessed for the presence and severity of hemosiderin deposition, fatty
liver disease, and hepatitis. Demographics, clinical pathology values, and
percentage weight loss were compared among dolphins with and without these
changes. Twelve (66.7%) dolphins had mild to moderate hemosiderin deposition, 7
(38.9%) had mild to severe fatty liver disease, and 11 (61.1%) had mild to
moderate hepatitis. Of the 12 dolphins with hemosiderosis, deposition occurred in
the Kupffer cells among 11 (91.7%). Dolphins with fatty liver disease were more
likely to have higher postprandial serum hyperglycemia (>140 mg/dl), leukocytosis
(>11,000 cells/microl), and hyperglobulinemia (>3.5 g/dl). Unlike in many
nonhuman terrestrial animals, fatty liver disease was not associated with rapid
weight loss or hypoglycemia. Interestingly, there were no significant
associations among dolphins with hemosiderosis, fatty liver disease, and
hepatitis. This study supports that both hemochromatosis and fatty liver disease
were present in the dolphin study population, and histopathology and clinical
pathology among these animals suggest a nonhereditary, metabolic etiology.
KEYWORDS: Bottlenose dolphin, fatty liver disease, hemochromatosis,
hemosiderosis, hepatic lipidosis, hepatitis, Tursiops truncatus.
PMID- 23156705
TI - Black rhinoceros (Diceros bicornis) natural diets: comparing iron levels across
seasons and geographical locations.
AB - Although excessive iron storage in black rhinoceros (Diceros bicornis) has been a
cause for continuous concern over the last four decades and differences in the
iron content of diet items fed in captivity and in the wild have been documented,
no reports exist on the iron content of the total diet ingested by free-ranging
animals. Here, the results of field studies using backtracking to record the
ingested diets of black rhinoceros from three habitats across three seasons are
reported. Levels of iron and of condensed tannins, which might reduce iron
availability, averaged at 91 +/- 41 ppm dry matter and 3.0 +/- 1.0% dry matter,
respectively, across all habitats and seasons. Although geographic and seasonal
variation was significant, these differences are of a much lower magnitude than
differences between the averages of these diets and those fed to black rhinoceros
in captivity. The results can provide guidelines for the iron content of diets
designed for black rhinoceros and suggest that the effect of tannins in these
species should be further investigated.
PMID- 23156706
TI - Serum iron and selected biochemical values in free-ranging black rhinoceros
(Diceros bicornis) from South Africa.
AB - Serum samples collected from 20 black rhinoceros (Diceros bicornis) were analyzed
for iron values from six different areas in South Africa. In addition,
biochemical profiles were performed on individual samples. Comparisons of iron
values from free-ranging black rhinoceros and from 28 free-ranging white
rhinoceros (Ceratotherium simum) were conducted by location and age. Among the
free-ranging black rhinoceros, samples were compared from different regions to a
set of samples from black rhinoceros that had been captured and held in bomas.
Serum iron levels were not significantly different (P = 0.55) among the three
locations with more than one animal (medians 5.57, 5.70, 6.47 ppm), but the
median value from the boma group was significantly lower (2.91 ppm; P = 0.042),
contrary to previous studies. Similar to reports in captive black rhinos, serum
iron levels appeared to show a trend toward increasing values between subadult
and adult animals, although differences were not statistically significant among
black rhinoceros. Comparison of serum iron levels between free-ranging black and
white rhinoceros showed significantly higher median value in black rhinoceros
(5.73 ppm) versus white rhinoceros (3.38 ppm, P= 0.001). Other significant
differences (P < 0.05) in biochemical values between species included lower
median aspartate aminotransferase (37 versus 76.5 U/L), higher copper (1.50
versus 1.34 ppm), higher zinc (1.36 versus 0.37 ppm), lower total protein (8.0
versus 10.35 g/dL), higher gamma glutamyltransferase (13.0 versus 12.5 U/L), and
lower globulin (6.6 versus 7.6 g/dL) in black rhinoceros. Further investigations
should be conducted to examine the role of age, location, and time in boma
confinement on iron values in South African rhinoceros to understand iron
metabolism in these species.
PMID- 23156707
TI - A potential link between insulin resistance and iron overload disorder in
browsing rhinoceroses investigated through the use of an equine model.
AB - Iron overload disorder afflicts captive rhinoceros but has not been documented in
the wild. The specific cause for the disorder has not been identified but is
likely associated with diet and management. Compared with wild counterparts,
captive rhinoceros eat diets containing more iron, have greater fat stores, and
exercise less. It has been suggested that the problem may be linked to
development of insulin resistance in the captive population. Given that
controlled experiments with sufficient numbers of rhinoceros are logistically not
possible, an equine model was used to look for a relationship between iron status
and insulin resistance; the nutritional requirements of horses are used as a
guide for rhinoceros, because they have similar gastrointestinal tracts. Sixteen
horses were tested to determine blood insulin responses to an oral drench of
dextrose (0.25 g/kg bodyweight) and a meal of pelleted corn (1.5 g/kg
bodyweight). Fasting blood samples were taken 30 and 0 min before administration.
Further blood samples were taken every 30 min for 4 hr after administration to
determine peak insulin and total area under the insulin curve (AUC). Fasting
samples were tested for serum ferritin concentrations. Correlations were
determined between ferritin and peak insulin concentrations and insulin AUC after
administration of oral dextrose and pelleted corn. The strongest correlation was
between ferritin and insulin AUC after dextrose administration (r = 0.61; P =
0.01) followed by AUC after feeding a meal of pelleted corn (r = 0.60; P = 0.01),
with the correlation for peak insulin being 0.53 (P = 0.03) after dextrose
administration and 0.56 (P = 0.02) after pelleted corn. When evaluating responses
by gender, a significant correlation existed only for females, influenced by one
insulin resistant individual. These data suggest a potential link between insulin
resistance and body stores of iron and also suggest that approaches to reduce the
susceptibility to insulin resistance should be incorporated into management of
captive browsing rhinoceros.
PMID- 23156708
TI - Browse diversity and iron loading in captive sumatran rhinoceroses (Dicerorhinus
sumatrensis): a comparison of sanctuary and zoological populations.
AB - Iron storage disease (ISD) is now recognized as a serious clinical disorder
acquired by two species of browsing rhinoceroses, the African black (Diceros
bicornis) and the Asian Sumatran (Dicerorhinus sumatrensis) rhinoceroses, when
displaced from their natural habitats. The most complete knowledge of ISD comes
from studies of the black rhinoceros, but the Asian species is also at risk.
Sumatran rhinoceroses housed in traditional zoological settings outside of range
countries have suffered significant morbidity and mortality potentially related
to ISD induced by diet and/or other confinement conditions. With so few animals
in captivity, very little information exists on iron loading in the Sumatran
rhinoceros. To better characterize the problem, we retrospectively compared
captive management conditions of Sumatran rhinoceroses housed under traditional
zoological care with those in two native sanctuary environments. In general, zoo
rhinoceroses are offered a paucity of plants and browse species compared with
their sanctuary and wild counterparts managed in native rainforest habitats. Iron
analyte levels and limited histopathologic observations in these populations
suggest variable tendencies to overload iron, dependent upon differences in
managed diet and individual food preferences. More detailed investigation of
these markedly dissimilar ex situ populations is warranted to better understand
the role of nutrition and other conditions affecting iron loading in browser
rhinoceroses.
PMID- 23156709
TI - Plant phenolics and their potential role in mitigating iron overload disorder in
wild animals.
AB - Phenolic compounds are bioactive chemicals found in all vascular plants but are
difficult to characterize and quantify, and comparative analyses on these
compounds are challenging due to chemical structure complexity and inconsistent
laboratory methodologies employed historically. These chemicals can elicit
beneficial or toxic effects in consumers, depending on the compound, dose and the
species of the consumer. In particular, plant phenolic compounds such as tannins
can reduce the utilization of iron in mammalian and avian consumers. Multiple zoo
managed wild animal species are sensitive to iron overload, and these species
tend to be offered diets higher in iron than most of the plant browse consumed by
these animals in the wild and in captivity. Furthermore, these animals likely
consume diets higher in polyphenols in the wild as compared with in managed
settings. Thus, in addition to reducing dietary iron concentrations in captivity,
supplementing diets with phenolic compounds capable of safely chelating iron in
the intestinal lumen may reduce the incidence of iron overload in these animal
species. It is recommended to investigate various sources and types of phenolic
compounds for use in diets intended for iron-sensitive species. Candidate
compounds should be screened both in vitro and in vivo using model species to
reduce the risk of toxicity in target species. In particular, it would be
important to assess potential compounds in terms of 1) biological activity
including iron-binding capacity, 2) accessibility, 3) palatability, and 4)
physiological effects on the consumer, including changes in nutritional and
antioxidant statuses.
PMID- 23156710
TI - Management strategies of iron accumulation in a captive population of black
rhinoceroses (Diceros bicornis minor).
AB - During routine health screens for black rhinoceroses (Diceros bicornis minor) in
a captive setting, serum iron and ferritin were analyzed as well as total iron
binding capacity and total iron saturation. Trends for ferritin and percent iron
saturation showed steady increases since 2003 in four of four animals (three
males; one female) with two animals (one male; one female) consistently showing
higher elevations over conspecifics. The historical diet had been comprised of a
commercial or in-house complete pelleted feed; several species of fresh browse,
Bermuda grass, alfalfa and timothy hays, as well as enrichment and training items
(apples, carrots, sweet potatoes, and a small amount of leafy greens and
vegetables). In 2009, one of the three male rhinoceroses showed a threefold
increase in ferritin and concurrently exhibited clinical signs of lethargy,
decreased appetite, and disinterest in training. The lone female showed a twofold
increase; she also became reproductively acyclic in the prior year. The male was
immobilized for examination and phlebotomy. During the same time period, a new
version of the complete pelleted feed, with a reduced amount of iron, was
introduced. Subsequent to the diet change, the male's ferritin levels have
consistently declined, and the female started cycling again. Even with these
corrective steps to reduce iron levels, levels of iron saturation remained high,
and ferritin levels were still above 1,500 ng/ml. Therapeutic phlebotomy was
instituted via a rigorous training program that allowed phlebotomies over a 30
min time frame. This was possible because of a long-term training program for the
animals, consistent training personnel, routine collection of samples on a
monthly basis, and general comfort level of the animals in the restraint chute.
The results of this integrated approach showed some significant improvements and
an overall positive impact on the animals.
PMID- 23156711
TI - Review of laboratory and necropsy evidence for iron storage disease acquired by
browser rhinoceroses.
AB - Necropsies of two browser rhinoceroses, African black (Diceros bicornis) and
Sumatran (Dicerorhinus sumatrensis), often reveal extensive iron-pigment
deposition in various tissues. This condition (hemosiderosis) has not been
observed in species that are natural grazers, African white (Ceratotherium simum)
and Asian greater one-horned (Indian; Rhinoceros unicornis), nor in any species
free ranging in the wild. The causes, clinical significance, and consequences of
captivity-acquired hemosiderosis have remained controversial despite two decades
of compelling evidence that iron tends to accumulate logarithmically in all
members of affected species in proportion to periods of expatriation; total-body
iron loads can reach 10-fold in less than 3 yr and eventually exceed reference
ranges by two to three orders of magnitude; iron overburdens are accompanied by
laboratory and histopathologic evidence of cellular injury, necrosis and other
clinical consequences characteristic of chronic pathologic iron storage
[corrected] disorders (ISD) in humans and other species (hemochromatosis); and
that ISD develops in many other exotic wildlife species displaced from their
natural habitats. The historical evolution of evidence establishing the
development of pathologic ISD in browser (but not in grazer) rhinoceroses and the
possible relevance of ISD to other conditions affecting these two species will be
reviewed. Evidence reviewed includes new as well as published data derived from
quantitative measurements of iron analytes in sera and necropsy tissues and
histopathologic evaluations of current and past necropsies of captive and free
ranging rhinoceroses of all four available species. The evolutionary, husbandry,
and conservation implications of ISD in rhinoceroses are relevant to
understanding ISD acquired by many other species of exotic wildlife when
displaced from their natural environments.
PMID- 23156712
TI - IOD in rhinos--veterinary group report: report from the Clinical Medicine and
Pathology Working Group of the International Workshop on Iron Overload Disorder
in Browsing Rhinoceros (February 2011).
PMID- 23156713
TI - IOD in rhinos--nutrition group report: Report from the Nutrition Working Group of
the International Workshop on Iron Overload Disorder in Browsing Rhinoceros
(February 2011).
PMID- 23156714
TI - IOD in rhinos--epidemiology group report: report from the Epidemiology Working
Group of the International Workshop on Iron Overload Disorder in Browsing
Rhinoceros (February 2011).
PMID- 23156715
TI - IOD in rhinos--immunity group report: report from the Immunity, Genetics and
Toxicology Working Group of the International Workshop on Iron Overload Disorder
in Browsing Rhinoceros (February 2011).
PMID- 23156716
TI - [Roles of gap junctions in proliferation mediated by Hcy in the spontaneous
hypertensive rat vascular smooth muscle cells].
AB - OBJECTIVE: To investigate whether homocysteine (Hcy) participates the
proliferation of the spontaneously hypertensive rat(SHR) vascular smooth muscle
cell (VSMCs) and the molecular mechanism. METHODS: The rat's arota were removed.
The primary SHR VSMCs were isolated and cultured in vitro, then the SHR VSMCs
were divided into four groups: (1) control group, (2) Hcy group, (3) 18alpha
glycyrrhetinic acid (GA) group, (4) Hcy + 18alpha-GA group. We detected
proliferation of the SHR VSMCs by MTT and flow cytometry. The expression and co
localization of the connexin (Cx) 43 and Cx40 proteins in the SHR VSMCs were
deteced by immunofluorescence. The expression of the Cx43 and Cx40 proteins in
SHR VSMCs were detected by Western blot. The molecular dye transfer method
(scrape dye transfer method) was applied to detect the gap junction function in
the SHR VSMCs. RESULTS: (1) The Cx43 and Cx40 proteins expression in the SHR
VSMCs were positive, confocal microscopy supported the co-localization of Cx43
and Cx40 in the cytoplasm. (2) The S value deteced by cell cycle and A value
detected by MTT in the Hcy group were increased obviously compared with those in
the control group (P < 0.05), decreased in 18alpha-GA group (P < 0.05). Compared
with the Hcy group, the S and A value in the Hcy + 18alpha-GA group were
significantly decreased, respectively (P < 0.05). (3) The expression of Cx43 and
Cx40 proteins in Hcy group were increased compared with the control group (P <
0.05), decreased in 18alpha-GA group (P < 0.05). Compared with the Hcy group, the
expression of Cx43 and Cx40 proteins in the Hcy + 18alpha-GA group were
significantly decreased, respectively (P < 0.05). (4) The function of gap
junction detected by scrape dye transfer method in the Hcy group were enhanced
compared with the control group (P < 0.05), weakened in the 18alpha-GA group (P <
0.05). Compared with the Hcy group,the function of gap junction in the Hcy +
18alpha-GA group was significantly weakened (P < 0.05). CONCLUSION: Hcy can
enhance the function of gap junctional to stimulate the proliferation of SHR
VSMCs through the expression of Cx43 and Cx40 proteins promoted.
PMID- 23156717
TI - [Generation of Tau/App/PS1 triple-transgenic mouse model and the study of its
biological characteristics].
AB - OBJECTIVE: To establish the triple-transgenic mouse model and study their
biological characteristics by molecular biology, behavior and pathology. METHODS:
Hybrid the Tau and amyloid precursor protein (APP)/presenilins (PS1) transgenic
mouse, the genotype of offspring mice were identified by PCR. Transcribed target
genes were detected by RT-PCR. The protein expression of exogenous genes was
detected by Western-blot. The pathological change of neurofibrillary tangles and
senile plaque were observed by Bielschowsky silver staining and ABC
immunohistochemical method. The changes time of learning and memory were observed
by Morris water maze. RESULTS: APP, PS1 and Tau genes were transcript in
Tau/APP/PS1 mice. In 6 to 8 months old Tau/APP/PS1 mice, the neurofibrillary
tangles and senile plaque could be found in cortex and hippocampus. In 6 months
old Tau/APP/PS1 mice, the learning and memory abilities were worse. CONCLUSION:
With the behavior change and pathological changes in Tau and beta-amyloid protein
(AP), the Tau/APP/PS1 triple-transgenic mice can be used as a further study
animal model of AD's pathogenesis and the target of drug treatment.
PMID- 23156718
TI - [The variation of PPAR pathway molecules in the lung tissue of rats under
hyperbaric oxygen exposure].
AB - OBJECTIVE: To study the expression pattern of peroxisome proliferator-activated
receptor (PPAR) pathway molecules in rat lung tissue under hyperbaric oxygen
exposure. METHODS: Twenty seven male SD rats were randomly divided into
hyperbaric normoxia group (0.23 MPa air), hyperbaric oxygen treatment time series
group (0.23 MPa oxygen, were exposed for 2 h, 4 h, 6 h or 8 h), continuous small
flow of ventilation to maintain cabin O2 concentration > 99%. HE staining of lung
tissue morphological changes and application oligo microarray to each time point
lung were observed. Part of the PPAR pathway genes were validated by RT-PCR.
RESULTS: Compared with hyperbaric normoxia group, the lung injury caused by
hyperbaric oxygen treatment gradually deteriorated during the time series.
Expression microarray analysis of gene ontology (Go) enrichment analysis results
in a class of PPAR pathway class included multiple PPAR pathway molecule. RT-PCR
results suggested that PPAR-8 and PPAR-Y were up-regulated in the lung tissue
after a long time exposure to hyperbaric oxygen. CONCLUSION: Pro-longed
hyperbaric oxygen exposure causing pulmonary oxygen toxicity can induce the
activation of the PPAR pathway.
PMID- 23156719
TI - [Effects of taurine on the ultrastructure and P2X7 receptor expression in brain
following traumatic brain injury in rats].
AB - OBJECTIVE: To explore the effects of taurine on the ultrastructure and P2X7
receptor protein expression in brain following traumatic brain injury (TBI) in
rats. METHODS: Forty male SD rats, were divided randomly into four groups that
were sham-operated group, TBI group, TBI plus low-dose taurine group and TBI plus
high-dose taurine group. The TBI model was established by Marmarou's method, the
expression of P2X7 receptor protein in parietal cortex and hippocampus was
detected by the immunohistochemical method, the ultrastructure of parietal cortex
were observed by transmission electron microscope. RESULTS: Compared with sham
operated group, the positive expression cells of P2X7 receptor protein in
parietal cortex and hippocampus of TBI group were significantly increased (P <
0.01). Compared with TBI group, the positive expression cells of P2X7 receptor
protein in parietal cortex and hippocampus of TBI plus low-dose taurine group and
TBI plus high-dose taurine group were significantly decreased (P <0.01 or P
<0.05). Compared with TBI plus low-dose taurine group, the positive expression
cells of P2X7 receptor protein in parietal cortex and hippocampus of TBI plus
high-dose taurine group were significantly decreased (P < 0.05 or P < 0.01). The
pathological damage of parietal cortex in the TBI plus high-dose taurine group
was obviously lightened. CONCLUSION: Taurine exerts the neuroprotective effect on
TBI in rats, the protective mechanism might be associated with down-regulating
the expression of P2X7 receptor protein in parietal cortex and hippocampus.
PMID- 23156720
TI - [Effects of microRNA-1 on negatively regulating L-type calcium channel beta2
subunit gene expression during cardiac hypertrophy].
AB - OBJECTIVE: To investigate the negative regulation of microRNA-1 (miR-1) on L-type
calcium channel beta2 subunit (Cavbeta 2) during cardiomyocyte hypertrophy and
its mechanism. METHODS: Cardiomyocyte hypertrophy was induced by isoproterenol
(ISO). The cell surface area was measured by image analysis system (HJ2000). The
targets of miR-1 were predicted by online database microCosm. The 3' untranslated
region sequence of Cavbeta 2 was cloned into luciferase reporter vector and then
transiently transfected into HEK293 cells. The luciferase activities of samples
were measured to verify the expression of luciferase reporter vector. The
expression of atrial natriuretic peptide (ANP), beta-myosin heavy chain (beta
MHC), miR-1 and the Cavbeta 2 mRNA were detected by qRT-PCR. The protein
expression of Cavbeta 2 was detected by Western blot. The level of miR-1 was up
regulated by miR-1 mimic transfection and the expression level of Cavbeta 2 was
down-regulated by RNAi, then effects of which on cardiomyocyte hypertrophy were
investigated. RESULTS: (1) The expression of miR-1 was significantly reduced in
cardiomyocyte hypertrophy. Upregulating the miR-1 level could suppress the
increase of cell surface area, the expression of ANP and beta-MHC mRNA (P <
0.05). (2) Cavbeta 2 was the one of potential targets of miR-1 by prediction
using online database microCosm. The luciferase activities of HEK293 cells with
the plasmid containing miR-1 and wide type Cavbeta 3' UTR sequence was
significantly decreased when compared with that of control group (P < 0.01). Up
regulation of the miR-1 level could suppress the protein expression of Cavbeta 2.
(3) The expression of Cavbeta 2 was significantly increased in cardiomyocyte
hypertrophy induced by ISO. Downregulation of Cavbeta by RNAi could markedly
inhibit the increase of cell surface area, the expression of ANP and beta-MHC
mRNA. CONCLUSION: Cavbeta2 is one of potential targets of miR-1 by bioinformatics
prediction. The experiment data confirms that Cavbeta2 is truly the target of miR
1. MiR-1 can negatively regulate the expression of Cavbeta 2, resulting in the
decrease of intracellular Ca2+ content and the attenuation of cardiomyocyte
hypertrophy.
PMID- 23156721
TI - [The role of JNK in apoptosis of renal tubular epithelial cells in diabetic rats
with fluctuant high blood glucose].
AB - OBJECTIVE: To explore the signal transduction mechanisms of apoptosis in renal
tubular epithelial cells in diabetic rats with fluctuant high blood glucose.
METHODS: Healthy SD rats were randomly divided into 3 groups: normal control
group (A), stable high blood glucose group (B) and fluctuant high blood glucose
group (C). Diabetic rats were induced by intraperitoneal injection of
streptozotocin (STZ, 65 mg/kg), and the fluctuant high blood glucose animal model
was induced by intraperitoneal injection of ordinary insulin and glucose at
different time point every day. The superoxide dismutase (SOD) activity and the
content of malonaldehyde (MDA) in renal tissue homogenate were detected with
colorimetry. The protein expression of Nox4 and JNK were examined by
immunohistochemistry and Western blot. Apoptosis was assessed by terminal
deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL). RESULTS:
After 12 experimental weeks, significantly increased cell apoptosis, up
regulation of Nox4 and P-JNK expression in renal tubular epithelial cells were
observed in B and C groups compared with those in A group. The MDA content
increased and SOD activity decreased in renal tissue in B and C groups. Above
effects were more obviously shown in C group. CONCLUSION: Fluctuant high blood
glucose induced more apoptosis of renal tubular epithelial cell than stable high
blood glucose in diabetic kidney, which might be related to the activation of JNK
signal transduction pathway.
PMID- 23156722
TI - [Effects of progesterone on the expression of HIF-1alpha in cerebral cortex with
hypoxic-ischemic injury in neonatal rats].
PMID- 23156723
TI - [Research on the antioxidant effect of Enshi banqiao radix codonopsis on brain
ischemia/reperfusion (I/R)injury].
PMID- 23156724
TI - [Research of the mechanism for high glucose induced glomerular mesangial cell
express TNF-alpha].
PMID- 23156725
TI - [The attenuation of myocardial susceptibility to ischemia/reperfusion injury by
ischemic postconditioning in hypercholesteremia rats and the role of hypoxia
inducible factor-1alpha].
AB - OBJECTIVE: To explore whether ischemic postconditioning can attenuate the
myocardial injury induced by ischemia/reperfusion (I/R) in hypercholesteremic
rats and whether hypoxia inducible factor-1alpha (HIF-1alpha) play a role in the
protection. METHODS: Adult male Wistar rats received a high fat diet for 8 weeks
to prepare the hypercholesteremic models. Myocardial damage induced by
ischemia/reperfusion was evaluated by infarct size, creatine kinase (CK) activity
and myocardial apoptosis. HIF-1alpha mRNA level was detected by real time-RT-PCR
and the protein level was detected by Western blot. RESULTS: Myocardial infarct
size, CK activity, and caspase-3 activity induced by I/R were markedly increased
in hypercholesteremic rats compared with those in normal rats. Ischemic
postconditioning attenuated the myocardial injury in both normal rats and
hypercholesteremic rats, and increased HIF-1alpha protein level. There was a
significant linear inverse relationship between HIF-1alpha protein level and
infarct size (r = -0.802, P <0.01). CONCLUSION: Hypercholesteremia enhanced the
susceptibility of myocardia to ischemia/reperfusion injury. While ischemic
postconditioning markedly attenuated the increase of myocardial susceptibility to
I/R induced by hypercholesteremia. HIF-1alpha might be one of the mechanisms of
protection by ischemic postconditioning.
PMID- 23156726
TI - [Effects of rabbit limbs ischemia/ reperfusion on myocardial necrosis and
apoptosis].
AB - OBJECTIVE: To investigate the effects of rabbit limbs ischemia/reperfusion on
myocardial necrosis and apoptosis in vivo. METHODS: Thirty-six healthy new
zealand rabbits were randomly divided into 3 groups: (1) Sham group; (2)
I/R(Ischemia/reperfusion) group; (3) RPostC (remote postconditioning) group. The
activity of blood serum creatine kinase (CK) and lactate dehydrogenase (LDH) were
measured at baseline, the end of ischemia after 60 min and 120 min of reperfusion
respectively. The extent of myocardial ischemia and the scope of myocardial
infarction were assessed by evans blue and Triphenyl tetrazolium chloride (TTC).
The myocardial cell's apoptosis at the area of myocardial ischemia was estimated
by Tunel. Protein expression of caspase-3, Bcl-2 and Bax in myocardial ischemic
area were analyzed with the method of immunohistochemistry. RESULTS: Compared
with I/R group, the myocardial infarct size and the CK activity were
significantly reduced in RPostC group. The Tunel positive index of RPostC group
in ischemic myocardium was significantly lower than that in I/R group (21.79% +/-
1.07% vs 35.81% +/- 1.10%, P < 0.05). Caspase-3 positive cells index was
calculated with randomly selected five regions in each slide and then the
positive cells in per hundred cells were calculated. The RPostC group of caspase
3 positive cells was significantly lower than that in I/ R group(25.03% +/- 1.16%
as 39% +/- 2.43%, P < 0.05). Compared with the sham group, the Bax protein
expression index and the Bcl-2 protein expression index of I/R group and RPostC
group were increased. The Bax/Bcl-2 ratio of RPostC group decreased, while it was
increased in I/R. Compared with the I/R group, the Bax protein expression and
Bax/Bcl-2 ratio of RPostC group significantly reduced, but the expression index
of Bcl-2 ratio was significantly increased, the differences were statistically
significant. CONCLUSION: Limbs ischemia/postconditioning could significantly
reduce necrosis and apoptosis of ischemia/reperfusion myocardium. The mechanism
of reducing the myocardial cell apoptosis may have relation to inhibiting the
activation of pro-apoptotic gene caspase-3 and increased expression of Bcl-2.
PMID- 23156727
TI - [Changes of protein kinase A expressions in central amygdaloid nuclei during the
process of chronic morphine-induced conditioned place aversion in rats].
AB - OBJECTIVE: To explore neurobiological mechanisms of the withdrawal-induced
aversion. The changes of protein kinase A were measured in central amygdaloid
nucleic (CeA) of conditioned place aversion (CPA) model rats. METHODS: (1) All 72
male SD rats were divided into three groups, model group (MN group), and control
group (MS group and SN group). MN group was injected with morphine,6.5 days, 10
mg/kg, intraperitoneally (ip), twice per day, naloxone injection, 0.3 mg/kg, ip,
along with conditioned place aversion training, to develop the CPA model. The MS
group was administrated equivalent volume of morphine and saline. Also the SN
group was injected with equivalent volume of saline and naloxone. (2) During the
process of morphine-induced CPA, the expression of protein kinase A was assayed
with immunohistochemistry in the CeA. RESULTS: In the MN group, protein kinase A
expressions in the CeA occurred adaptive changes at different points of CPA (P <
0.05). Protein kinase A expressions after establishment(Day7,134.43 +/- 4.481, P
< 0.05), and after extinction (Day 13, 141.01 +/- 3.360, P < 0.01), and after
reinstatement (Day 14,137.18 +/- 40.330, P < 0.05) were also lower than those
before the establishment of the CPA (Day 5, 124.48 +/- 6.722). However, PKA
expressions were not significantly different both in MS group (P > 0.05)and SN
group (P > 0.05). CONCLUSION: (1) Protein kinase A expression, in turn regulating
the aversion expression, in the CeA probably is a key pathway contributing to the
development of CPA. (2) The neuroadaptation mediated by protein kinase A may be
one of the important molecular underpinnings of CPA.
PMID- 23156728
TI - [Effects of captopril on the protein expression of Bax and Bcl-2 in chronic
pressure overload rats].
PMID- 23156729
TI - [Effects of angiotensin II on the type of the skeletal muscle of amyotrophic
rat].
PMID- 23156730
TI - [The effect of Hsp72 on IL-6, IL-8 expression and activation of NF-kappaB in
synoviocytes of rheumatoid arthritis].
AB - OBJECTIVE: To investigate the effects of heat shock protein 72 (Hsp72) on the
expression of IL-6 and IL-8 and activation of NF-kappaB in synoviocytes from
patients suffered from rheumatoid arthritis (RA). METHODS: IL6 and IL8
concentrations in culture supernatants were measured using enzyme-linked
immunosorbent assays (ELISA). Nuclear translocation of NF-kappaB and degradation
of the inhibitory protein IkappaBalpha were examined using immunohistochemistry
and Western blot. RESULTS: Hsp72 down-regulated IL-6 and IL-8 production in RA
synoviocytes induced by tumor necrosis factor-alpha (TNF-alpha). Hsp72 inhibited
nuclear translocation of NF-kappaB and degradation of IkappaBalpha induced by TNF
alpha. CONCLUSION: Hsp72 has an anti-inflammatory effect on RA by down-regulation
of IL-6 and IL-8 in synoviocytes, which is mediated through inhibiting the
activation of NF-KalphaB signal pathways.
PMID- 23156731
TI - [Study of soft capsule of compound oil of jujube, arborvitae, and gardenia on
enhancing hypoxia tolerance and anti-fatigue in mice].
PMID- 23156732
TI - [Effect of telmisartan and pyridoxamine on oxidative stress in brain tissue of
spontaneously hypertensive rats].
AB - OBJECTIVE: To explore the effect of telmisartan and pyridoxamine on oxidative
stress in brain tissue of spontaneously hypertensive rats. METHODS: Twenty-four
spontaneously hypertensive rats were randomly divided into four groups (n = 6):
hypertensive control group (HC group), telmisartan group (T group ), pyridoxamine
group (P group ), telmisartan and pyridoxamine group (TP group). Wistar-Kyoto
(WKY) rats of the same age were served as a normal control group (NC group). Drug
treatment lasted for 16 weeks the level of hyde (MDA) in rat brain tissue, as
well as superoxide dismutase (SOD) activity and nicotinamide adenine dinucleotide
phosphate(NADHP) oxidase p47phox mRNA expression were observed in this study.
RESULTS: The MDA level in brain in HC group were higher than that in NC group and
the SOD activity were lower (P < 0.05). T group, P group and TP group had lower
MDA level and higher SOD activity than HC group (P < 0.05). The NADPH mRNA in
brain in HC group were significantly higher than that in NC group (P < 0.01). T
group and TP group had decreased levels of NADPH mRNA (P < 0.01), there was no
significant difference between HC group and P group (P > 0.05). CONCLUSION: The
brain tissue of spontaneous hypertensive rats had been under the status of
oxidative stress. Single application of either telmisartan or pyridoxamine could
inhibit oxidative stress of brain tissue. However, compare with single treatment
of telmisartan, no beneficial effects were observed in combined use of
telmisartan and pyridoxamine.
PMID- 23156733
TI - [Effects of CGRP on the E-cadherin expression in human bronchial epithelial
cells].
AB - OBJECTIVE: To discuss the effect of calcitonin gene-related peptides (CGRP) on
epithelial cadherin (E-cd) expression in human bronchial epithelial cells (HBECs)
in vitro. METHODS: The effect of CGRP on E-cd protein and mRNA expression in both
normal and O3-challenged HBECs were determined by immunocytochemistry and RT-PCR.
The signal transduction pathways of CGRP were observed by using protein kinase
C(PKC) inhibitor (H-7), calmodulin(CaM) inhibitor (W-7) and PKA inhibitor (H-89).
RESULTS: CGRP increased E-cd mRNA and protein expressions of normal and O3
challenged HBECs in a dose-dependent manner. CGRP had no effect on cytoplasm E-cd
expression. Pre-treatment with H-89, H-7 and W-7, the up-regulatory effect of
CGRP on E-cd expression was partly abolished. CONCLUSION: CGRP increased in
cytomembrane E-cd expression of normal and O3-challenged HBECs in a dose
dependent manner. E-cd expression on HBECs was strengthened by CGRP via PKA, PKC
and CaM pathways.
PMID- 23156734
TI - [Effect of resveratrol on expression of cdk5 in activation effect of LPS on N9
microglia cells].
PMID- 23156735
TI - [Changes in the mRNA expression of adiponectin, adiponectin receptors, and leptin
in adipose tissue of Wannanhua pigs at different stages of development].
AB - OBJECTIVE: To explore the changes in the mRNA expression of adiponectin (Adp),
adiponectin receptors(AdpR), and leptin in different adipose tissues of Wannanhua
pigs at different stages of development, and their sexual dimorphism. METHODS:
Five Wannanhua boars and five Wannanhua gilts were sampled at birth, 30, 45, 90,
and 180 days of age respectively. The delta delta Ct relative quantification real
time PCR was used to detect the transcription levels of Adp, AdpR1, AdpR2, and
leptin mRNAs in subcutaneous (SC) and perirenal (PR) adipose tissues, and beta
actin were used as internal standards. RESULTS: The expression level of Adp,
AdpR1, AdpR2, and leptin mRNA in SC and PR adipose tissue were changed with age
significantly (P < 0.01). In general, Adp mRNA expression in SC adipose tissue
was significantly lower than that in PR adipose tissue (P < 0.05), while AdpR1,
AdpR2, and leptin mRNA expression in SC adipose tissue were significantly higher
than those in PR adipose tissue (P < 0.05 or P < 0.01). Although the sexual
dimorphism were found in apart genes or apart days of age, Adp, AdpR1, AdpR2, and
leptin mRNA expression both in SC adipose tissue and PR adipose tissue had no
significant differences between Wannanhua gilts and boars in general. Significant
positive correlation was found between Adp and AdpR1, AdpR2 (P < 0.05 or P <
0.01), and significant negative correlation was found between Adp and leptin (P <
0.05) in SC adipose tissue and PR adipose tissue respectively (P < 0.05).
CONCLUSION: The expression of Adp, AdpR1, AdpR2, and leptin mRNA in adipose
tissue of Wannanhua pigs followed specific developmental patterns and tissue
specificity. Adp correlated with its receptors.
PMID- 23156736
TI - [Effects of HiLo for two weeks on erythrocyte immune adhesion and leukocyte count
of swimmers].
AB - OBJECTIVE: To investigate the effects of living high-training low (HiLo) on
innate immunity in blood of elite swimmers. METHODS: Six female swimmers
undertook HiLo for two weeks, erythrocyte adhesion function and counts of
leukocyte were tested in different time of training period. RESULTS: Red blood
cell C3b receptor ring rate (RBC-C3bRR) decreased and red blood cell immune
complex matter ring rate (RBC-ICR) increased significantly (P < 0.05), the two
markers returned to base line 1 week after training. Counts of leukocyte and
granulocyte decreased significantly (P < 0.05), and they recovered 1 week after
training; Counts of lymphocyte and monocyte decreased without significance during
training and did not recovered after training. CONCLUSION: Immunity of
erythrocyte and granulocyte decreased quickly, but lymphocyte and monocyte
recovered slowly, swimmers were adaptive to the training.
PMID- 23156737
TI - [Effect of chronic unpredictable stress on conditioning fear behavior and
somatosensory evoked potential of rats].
PMID- 23156738
TI - [Effect of Angelica on hippocampal neurons and gliocytes of neonatal rats after
intrauterine hypoxia].
PMID- 23156739
TI - [The effect of advanced glycosylation end products on the expression of
fibronectin and the regulation of protein kinase C in human peritoneal
mesothelial cells].
AB - OBJECTIVE: To study the effects of advanced glycosylation end products (AGEs) on
the production of fibronectin (FN) in human peritoneal mesothelial cells (HPMC)
in vitro and the role of protein kinase C (PKC) in this course. METHODS: The AGE
human serum albumin (HSA) (0, 100, 500, 1 000 microg/ml) was used in culture
medium to stimulate the HPMC. The mRNA level of FN was measured with real-time
PCR, moreover, the protein level of FN in HPMC was detected by ELISA. With the
method of ELISA, the PKC activities were observed. Inhibitors or activators of
PKC were used to observe the roles of PKC pathways on the AGE-HSA stimulated
productions of FN in HPMC. RESULTS: AGE-HSA activated PKC in HPMC in a dose, time
dependent manner (P < 0.05). AGE-HSA up-regulated the expression of FN mRAN and
protein in dose- and time-dependently (P < 0.01); PKC activator phorbol 12
myristate 13-acetate (PMA) induced FN expression, respectively depletion of PKC
and calphostin C, a PKC inhibitor, effectively prevented both PMA and AGE-HSA
induced expression of the FN (P < 0.05). CONCLUSION: AGEs can increase the
activities of PKC. AGEs can directly increase FN expression in HPMC which may
contribute to peritoneal fibrosis and this is regulated by PKC.
PMID- 23156740
TI - [Change of adhesion molecules in the lungs of rat with decompression sickness].
AB - OBJECTIVE: To investigate the change of adhesion molecules in the lungs of rats
suffered with decompression sickness (DCS). METHODS: Male SD rats were placed in
the hyperbaric chamber, the chamber was compressed within 3 minutes to depths of
7 absolute atmosphere (ATA) and held at the designated depth for 60 min, then
rapidly decompressed (3 min) to the surface. Rats were observed for signs of DCS
after decompression. The brains, hepatis, and lungs were removed at 30 min, 6 h,
24 h post decompression, fixed and stained with hematoxylin eosin for routine
histologic analysis. Lung paraffin sections were immunostained for the expression
of intercellular adhesion molecule-1 (ICAM-1), E-selectin and major
histocompatibility complex class II molecule (MHC-II). 2% evans blue dye in
normal saline was injected 30 minutes prior to 6 h, 24 h before decompression.
After 30 min, animals were perfused with 0.9% normal saline and lungs were
harvested. Evans blue in the plasma was quantified by wavelength
spectrophotometric analysis at 620 nm. RESULTS: Results showed that there were
hemorrhage and edema changes in the lungs, liver and brain at 30 min post
decompression. Compared with control animals maintained at 1 ATA, the levels of E
selectin, ICAM-1 and MHC-II in the lungs of DCS rats were significantly increased
post decompression. Compared with control animals, evans blue in the plasma was
much higher at 6 h, 24 h post decompression. CONCLUSION: The bubble-induced
adhesion molecule-mediated endothelial activation may be involved in the
pathogenesis of DCS.
PMID- 23156741
TI - [Study on neuroprotective effects of astragalan in rats with ischemic brain
injury and its mechanisms].
AB - OBJECTIVE: To study the effects of astragalan (AG) on the expression of the
neural cell adhesion molecule(NCAM) and c-fos of hippocampus CA1 region after the
ischemic brain injury in rats. METHODS: One hundred male Wistar rats (180-220 g)
were divided into ten groups randomly, they were sham operated group (SOG, n =
10), three model group(MG-ld, 3d, 7d, n = 10), as well as three low and high dose
astragalan treatment groups (L/H-AGTG-1d, 3d, 7d, n = 10), respectively. And
then, middle cerebral artery of MG and AGTG were intercepted by operation
inducing brain injured. Their cerebral blood vessel were reperfused on 1, 2, 3 d,
respectively, after the L/H-AGTG were treated with the AG (5 mg/kg and 15 mg/kg,
ip). After neurologic impairment(NIP) was scored, animals were decapitated to
take out hippocampus for counting apoptosis , determining the expression of the
NCAM and c-fos by immunohistochemistry method and RT-PCR semiquantitative
analysis, respectively. RESULTS: The NIP scores and apoptotic cell of the L-AGTG
and H-AGTG were significantly lower than MG (P < 0.05 or P < 0.01). The
expression of NCAM and c-fos were significantly higher than the MG (P < 0.05 or P
< 0.01). CONCLUSION: Astragalan could improve significantly neural function of
ischemia brain injury in rats,the mechanism concerned probably with blocking or
reversing apoptosis of hippocampus by promoting the expression of the NCAM and c
fos of hippocampus CA1 region.
PMID- 23156742
TI - [Protective effect of terpenes from fructus corni on the cardiomyopathy in
alloxan-induced diabetic mice].
AB - OBJECTIVE: To investigate the protective effects of terpenes from fructus corni
(TFC) on diabetic cardiomyopathy (DCM). METHODS: Diabetes was produced by a
single injection of alloxan (220 mg/kg, i.p.) in mice. The fasting blood glucose
of mice were tested 15 days later and that greater than 13.9 mmol/L were regarded
as the diabetic mice which were divided randomly into the model and TFC groups.
TFC dissolved by physiological saline (P.O, 80 mg/kg) was administrated to the
TFC group for successive 8 weeks since the 15th day. RESULTS: Compared to the
control group, the weight index increased significantly. The level of superoxide
dismutase (SOD) was markedly decreased and malondialdehyde(MDA), the inflammatory
factors (TNF-alpha, IL-6) were obviously increased in myocardium. The
histopathological examination suggested that myocardial cells disarranged,
swelling and the intercellular space increased in model group. It also showed the
infiltration of inflammatory cells and fibroblasts in TFC group. The above change
was improved significantly. CONCLUSION: TFC ameliorated the alterations of
cardiomyopathy in diabetic mice induced by alloxan. the mechanism might be
related to decrease blood glucose, antioxidative stress and inflammatory factors.
PMID- 23156743
TI - [Construction and identification of the expression plasmid of SK2 (KCNN2) gene
from human atrial myocytes with overlapping PCR].
AB - OBJECTIVE: Small conductance calcium activated potassium channels type 2 (SK2)
play a crucial role in atrial repolarization. It is difficult to acquire the full
length of its coded gene KCNN2 by RT-PCR with one step. We aim to get the full
length of KCNN2 gene and construct the plasmid by Overlapping PCR, and further
more discuss the application of Overlapping PCR. METHODS: Total RNA was extracted
from human right atrial tissue and cDNA was acquired with reverse transcription.
Overlapping PCR was conducted with three pairs of primers which were designed
according to the sequence of KCNN2 (AY258141) gene. The expression plasmid of
pIRES-hrGFP-SK2 was constructed by directed cloning with restriction enzyme site
and identified by enzyme cutting and sequencing. RESULTS: Three parts of PCR
amplification were consistent with predicted size. The sequence of the plasmid
was consistent with the gene-bank data except two sites, however, which were the
same as gene in different tissues. CONCLUSION: The expression plasmid pIRES-hrGFP
SK2 was constructed successfully. Overlapping PCR is a good choice for amplifying
these genes with long size or low expression.
PMID- 23156744
TI - [The influence of laser induced damage points on characters of the laser
transmission].
AB - The production and increase of damage points in optical components under high
energy repetitive pulsed lasers is closely dependent on the effects of light beam
intensity modulation. In the present paper, the appearance of laser-induced
damage points on surface of K9 glass was observed. The damage is increased toward
center. In this way, the center of the focus of laser beam is fully cracked, and
the shell-like factures and the refractive-index changing region, which is caused
by phase transition, are arranged outward orderly. The transmittance spectrum
through the K9 glass and damage point were measured, indicating that the optical
transmittances can reduce by over 20% and the declining rate is related to the
area of damage points instead of the wavelength, which means that the full
fracture of the material will absorb laser energy completely and is similar to
the black body. The laser density detection with CCD shows that the damage points
can cause the distortion of laser transmission and the scattering effect plays a
major role. This kind of modulation effects by damage points can cause
inhomogeneity of the laser light intensity distribution, which can induce
diffusion of damage in optical components.
PMID- 23156745
TI - [Research on cells ablation characters by laser plasma].
AB - The study on the mechanism of laser ablated cells is of importance to laser
surgery and killing harmful cells. Three radiation modes were researched on the
ablation characteristics of onion epidermal cells under: laser direct
irradiation, focused irradiation and the laser plasma radiation. Based on the
thermodynamic properties of the laser irradiation, the cell temperature rise and
phase change have been analyzed. The experiments show that the cells damage under
direct irradiation is not obvious at all, but the focused irradiation can cause
cells to split and moisture removal. The removal shape is circular with larger
area and rough fracture edges. The theoretical analysis found out that the laser
plasma effects play a key role in the laser ablation. The thermal effects,
radiation ionization and shock waves can increase the deposition of laser pulses
energy and impact peeling of the cells, which will greatly increase the scope and
efficiency of cell killing and is suitable for the cell destruction.
PMID- 23156746
TI - [Study of cuttings identification using laser-induced breakdown spectroscopy].
AB - Cutting identification is one of the most important links in the course of
cutting logging which is very significant in the process of oil drilling. In the
present paper, LIBS was used for identification of four kinds of cutting samples
coming from logging field, and then multivariate analysis was used in data
processing. The whole spectra model and the feature model were built for cuttings
identification using PLS-DA method. The accuracy of the whole spectra model was
88.3%, a little more than the feature model with an accuracy of 86.7%. While in
the aspect of data size, the variables were decreased from 24,041 to 27 by
feature extraction, which increased the efficiency of data processing observably.
The obtained results demonstrate that LIBS combined with chemometrics method
could be developed as a rapid and valid approach to cutting identification and
has great potential to be used in logging field.
PMID- 23156747
TI - [Research on demodulation system for human body temperature measurement of
intelligent clothing based on arrayed waveguide grating].
AB - A system for demodulating distributed fiber Bragg grating sensors of the
intelligent clothing was researched and realized, which is based on arrayed
waveguide grating. The principle of demodulation method based on arrayed
waveguide grating was analyzed, intensity--demodulating method was used to
interrogate the wavelength of the fiber Bragg grating based on the building up of
an experimental platform, and demodulation experiment of pre and post series of
fiber Bragg grating was completed. The results show that the wavelength
demodulation of the system has high linearity for fiber Bragg grating, the system
gives a wavelength accuracy of 0.001 nm, and demodulation error caused by
crosstalk between different sensors is 0.0005 nm. The measurement error of human
body temperature is +/- 0.16 degrees C. It can be applied to the human body
temperature measurement.
PMID- 23156748
TI - [Variation of irradiance in the arctic pole during the summer].
AB - The variation of irradiance affect the melting rate of the sea ice in the arctic
pole, and the research on it is an important component of the global climate
change research. The present research was based on the spectrum data collected
during the 4th scientific research on the arctic of China in 2010, analyzed the
variation of irradiance in the arctic pole during the summer and discussed the
reasons for the change. This research shows that many factors lead to the change,
among which the weather and the solar elevation angle affect the irradiance
directly. The weather factors determine the amount of solar radiation that
reached the ground after the absorption and attenuation of the clouds; In high
latitude areas, there is a low solar elevation angle and the attenuation of solar
radiation was obvious. Our research shows that the spectrum at shorter wavelength
is more sensitive to the changes in altitude of the sun, while the impact of
weather on the irradiance increases with wavelength. Moreover, moisture content
in the atmosphere also affects the solar radiation reaching the ground and the
its impact is in a particular band but not for the entire spectrum range.
PMID- 23156749
TI - [Impact analysis of atmospheric state for target detection in hyperspectral
radiance image].
AB - Target detection based on hyperspectral radiance images can improve data
processing efficiency to meet the requirements of real-time processing. However,
the spectral radiance acquired by the remote sensor will be affected by the
atmosphere. In the present paper, hyperspectral imaging process is simulated to
analyze the effects of the changes in atmospheric state on target detection in
hyperspectral radiance image. The results show that hyperspectral radiance image
can be directly used for target detection, different atmospheric states have
little impacts on the RXD detection, whereas the MF detection is dependent on the
accuracy of the input spectrum, and good results can only be obtained by the MF
detector when the atmospheric states are similar between the radiance spectrum of
the target to be detected and the simulated hyperspectral image.
PMID- 23156750
TI - [The solution of nonlinear function of ion mobility based on FAIMS spectrum peak
position].
AB - FAIMS's ion separation mechanism is based on analyte's characteristic nonlinear
relationship between its ion mobility and applied electric field strength.
Present characterization methods for this nonlinear relationship are based on
precarious assumptions which incur substantial errors under many circumstances. A
rigorous method for solving the second and fourth taylor series coefficient of
this relationship based on dispersion voltage value (assuming half-sinusoidal
waveform) and associated compensation voltage value of spectrum peak is
presented, alongside with rigorous analytical functions. FAIMS spectrums were
obtained for ethanol, metaxylene and n-butanol using custom-built FAIMS
spectrometer, and corresponding second and fourth taylor series coefficients were
obtained with the proposed method. Evaluation shows that this method
substantially reduces the RMS error between interpolated and measured peak
compensation voltage values under different dispersion voltages, confirming its
superiority over present methods. This rigorous method would help improve
spectral resolutions of FAIMS spectrometer, facilitating high precision FAIMS
spectrum database construction and accurate analyte discrimination.
PMID- 23156751
TI - [Research on the universal analytic potential function applied to diatomic
molecules].
AB - A new method on constructing analytical potential energy functions is presented,
and from this a analytical potential energy function applied to both neutral
diatomic molecules and charged diatomic molecular ions is obtained. In this
paper, the potential energy function is examined by 21 examples of eight
different basic kinds of diatomic molecules or ions--homonuclear ground-state for
neutral diatomic molecule Na2-X1 sigma g+, homonuclear excitation-state for
neutral diatomic molecule C2-A1 pi(u), homonuclear ground-state for charged
diatomic molecular ion He2+ -X2 sigma u+, homonuclear excitation-state for
charged diatomic molecular ion N2+ -B2 sigma(u), heteronuclear ground-state for
neutral diatomic molecule NaLi-X1 sigma g+, heteronuclear excitation-state
neutral diatomic molecule BH-B1 sigma+, heteronuclear ground-state for charged
diatomic molecular ion (BC)- -X3 pi, and heteronuclear excitation-state for
charged diatomic molecular ion (CS)+ -A2 pi etc. The theoretical values of the
vibrational energy level of molecules calculated by the potential energy function
are compared with RKR (Rydberg-Klein-Rees) or experimental data, and as a
consequence, all the results are precisely consistent with RKR data.
PMID- 23156752
TI - [Photostimulated luminescence and color centers research in BaCl(x)Br(2-x):Eu2+
phosphors].
AB - Eu2+ doped BaCl(x)Br(2-x), phosphors were prepared by solid state method in the
present paper. The crystal structure and luminescent properties were studied by
XRD, excitation, emission, and photostimulation. The XRD patterns indicate
thatthe samples are single phase of BaCl(x)Br(2-x). The X-ray diffraction peak
shifts to larger angle as the value of X increases. The emission spectra is a
narrow band with a peak locating at 405 nm, which is attributed to the transition
of 4f(6)5d-->4f(7). The excitation spectrum excited by 405 nm is a broad band
ranging from 250-380 nm with a peak locating at 303 nm. The photostimulation
spectrum is a broad band ranging from 480-800 nm with a peak locating at 575 nm.
Through fitting the spectrum curve, the photostimulation spectrum is composed of
three bands with peaks locating at about 550, 610 and 685 nm. The three fitting
bands correspond to the three color-centers belonging to F(Cl-), F(C1-Br) and
F(Br-) centers, respectively. The photostimulation peaks show a blue shift with
increasing the ratio of Cl/Br.
PMID- 23156753
TI - [Study of using regional mineral spectra library and section noise filtering to
improve mineral identification accuracy].
AB - Aiming at the low accuracy of mineral identification with hyperspectral data, the
present article established regional spectra library on the basis of the study
area geological background, and presented a pretreatment method that filters the
original spectra by section. First, continuum based fast Fourier transform was
used to filter the noise among 2000-2200, 2250-2300 and 2350-2500 nm. Then apply
the rapid quantificational identification model with regional spectrum library
was used to dispose the processed spectra. The highest effective rate of the
result is 80%, and the highest accuracy rate is 67%. Compared with the
identification result of original spectra, the average accuracy rate was upgraded
by 17.7%, and the average effective rate was upgraded by 5.1%. Compared with the
identification result of all-filtered spectra, the average accuracy rate was
upgraded by 5.8%, while the average effective rate was upgraded by 39.8%. This
method, which could guarantee that the identification result contains the most
correct minerals and the fewest error ones, promoted mineral identification
accuracy. The result with higher accuracy is significant to rapid mineral
extraction work in field.
PMID- 23156754
TI - [Micro-FTIR mapping tracer for the heterogeneity growth of nitrogen impurities in
natural diamond from three localities in China].
AB - The geographic locality determination of diamonds is of great significance in
understanding the mantle evolution, restricting the illegal trade of conflict
diamonds, etc. In the present article, the in-situ analysis of micro-FTIR surface
scan technique was first applied to analyze 14 IaAB natural diamond specimens
from China's three commercial localities. According to the FTIR spectra of
diamonds, the nitrogen contents were calculated (1616 data points of FTIR) and
used for mapping tracer. Th results showed that the nitrogen contents and its
aggregation often varied in the process of diamond growth, and the nitrogen
contents in initial nucleation stage could be higher or lower than in other
stages. It is not an unidirectional variation for nitroge contents in different
growth stages, indicating that the carbon and nitrogen had a complex exchange
with mantle fluid during the diamond's crystallization course. It was regionally
different between the diamonds from the three localities in the frequency
distribution of nitrogen contents and NB%/N(T). Micro-FTIR mapping is more
intuitive than the method of selecting discontinuous points, and it can trace the
heterogeneous growth of nitrogen impurities in natural diamonds consecutively.
PMID- 23156755
TI - [Quantitative prediction of soil salinity content with visible-near infrared
hyper-spectra in northeast China].
AB - Studying the spectral property of salinized soil is an important work, for it is
the base of monitoring soil salinization by remote sense. To investigate the
spectral property of salinized soil and the relationship between the soil
salinity and the hyperspectral data, the field soil samples were collected in the
region of Northeast China and then reflectance spectra were measured. The partial
least squares regression (PLSR) model was established based on the statistical
analysis of the soil salinity content and the reflectance of hyperspectra. The
feasibility of soil salinity prediction by hyperspectra was decided by analyzed
calibration model and independent validation. Models accuracy was also analyzed,
which was established in the conditions of different treatment methods and
different re-sampling intervals. The results showed that it was feasible to
predict soil salinity content based on measured reflectance spectrum. The results
also revealed that it was necessary to smooth measured hyperspectra for spectral
prediction accuracy to be improved significantly after smoothing. The best model
was established based on smoothed and log(l/x) transformed hyperspectra with high
determination coefficients (R2) of 0.6677 and RPD = 1.61, which showed that this
math transformation could eliminate noise effectively and so as to improve the
prediction accuracy. The largest re-sampling interval is 8 nm that could meet the
accuracy of the soil salinity prediction. Therefore, it provided scientific
reference of monitoring soil salinization by remote sensing from satellite
platform.
PMID- 23156756
TI - [Transfer calibration for alcohol determination using temperature-induced
shortwave near infrared spectra].
AB - The authors studied the temperature influence on short-wave near-infrared spectra
of ethanol aquatic solution and utilized four methods to establish the transfer
partial least squares (PLS) calibration model: direct transfer calibration,
global calibration, orthogonal signal correction (OSC) and generalized least
squares weighting (GLSW). The PLS models were built at four temperatures: 15, 25,
35 and 40 degrees C. The results showed that direct calibration provided high
prediction bias: significantly high positive prediction bias for a temperature
lower than calibration temperature and negative bias for higher temperatures. By
using the global correction, OSC and GLSW, the systematic errors could be
reduced. However, the global correction needed more calibration samples and built
a more complex model. The OSC and GLSW methods provided better predictions using
fewer latent variables. By using the GLSW method, prediction bias less than 0.1%
and RMSEP less than 0.9% were obtained. The absolute prediction error of GLSW
method was less than 1.5%. Additionally, the GLSW provided smaller prediction
error at every researched temperature using fewer latent variables than OSC.
Thus, GLSW was superior to OSC and could establish more robust transfer
calibration model.
PMID- 23156757
TI - [Infrared spectrum denoising with combination of lifting wavelet domain
thresholding and median filtering].
AB - Infrared spectra are often corrupted by noise, which may greatly influence the
accuracy and precision of the analytical result. To improve the analytical
precision, the authors need to denoise the spectrum data first. In the present
paper, a spectrum denoising method by the second generation wavelet transform
domain thresholding combined with the median filtering is introduced. The
spectrum of a certain kind of wheat was used to test the performance of the
proposed denoising method. In the experiment,noise with signal to noise ratio
21.17 dB was first added to the spectrum, and then removed by the proposed
denoising method. The signal to noise ratio (SNR), the root mean square error
(RMSE), the average relative error of the peak value (AREPV) and the average
error of the peak position (AEPP) were used to evaluate the performance of the
proposed denoising method. Experimental results show that the proposed method can
remove the spectrum noise and keep the useful information more effective than
Donoho's soft and hard threshold method. At the same time, it can achieve a
higher PSNR, a lower RMSE, a lower AREPV and a lower AEPP than the other two
denoising methods.
PMID- 23156758
TI - [Research on the combustion mechanism of asphalt and the composition of harmful
gas based on infrared spectral analysis].
AB - By using the Rosemount gas analyzer and the test platform of fixed bed built by
carbon furnace, the harmful gaseous compositions and the release rules of asphalt
and mortar under high temperature rate were analyzed quantitatively based on
infrared spectral analysis technology. The results indicated that the combustion
process of the asphalt and mortar can be approximately divided into two stages
stage of primary volatile combustion, and stage of secondary volatile release
combined with fixed carbon combustion in isothermal condition with high heating
rate. The major gaseous products are CO2, CO, NO, NO2 and SO2. the volatile
content is one of the key factors affecting the release rules of gaseous
combustion products in asphalt, and reducing the volatile content in asphalt
materials can effectively reduce the generation of gaseous combustion products,
especially CO.
PMID- 23156759
TI - [Nondestructive discrimination of strawberry varieties by NIR and BP-ANN].
AB - Strawberry variety is a main factor that can influence strawberry fruit quality.
The use of near-infrared reflectance spectroscopy was explored discriminate among
samples of strawberry of different varieties. And the significance of difference
among different varieties was analyzed by comparison of the chemical composition
of the different varieties samples. The performance of models established using
back propagation-artificial neural networks (BP-ANN), least squares-support
vector machine and discriminant analysis were evaluated on spectra range of 4545
9090 cm(-1). The optimal model was obtained by BP-ANN with a topology of 12-18-3,
which correctly classified 96.68% of calibration set and 97.14% of prediction
set. And the 94.95%, 97% and 98.29% classifications were given respectively for
"Tianbao" (n=99), "Fengxiang" (n=100) and "Mingxing" (n=117). One-way analysis of
variance was made for comparison of the mean values for soluble solids content
(SSC), titratable acid (TA), pH value and SSC-TA ratio, and the statistically
significant differences were found. Principal component analysis was performed on
the four chemical compositions, and obvious clustering tendencies for different
varieties were found. These results showed that NIR combined with BP-ANN can
discriminate strawberry of different varieties effectively, and the difference in
chemical compositions of different varieties strawberry might be a chemical
validation for NIR results.
PMID- 23156760
TI - [Rapid determination of fatty acids in soybean oils by transmission reflection
near infrared spectroscopy].
AB - In the present research, a novel method was established for determination of five
fatty acids in soybean oil by transmission reflection-near infrared spectroscopy.
The optimum conditions of mathematics model of five components (C16:0, C18:0,
C18:1, C18:2 and C18:3) were studied, including the sample set selection,
chemical value analysis, the detection methods and condition. Chemical value was
analyzed by gas chromatography. One hundred fifty eight samples were selected,
138 for modeling set, 10 for testing set and 10 for unknown sample set. All
samples were placed in sample pools and scanned by transmission reflection-near
infrared spectrum after sonicleaning for 10 minute. The 1100-2500 nm spectral
region was analyzed. The acquisition interval was 2 nm. Modified partial least
square method was chosen for calibration mode creating. Result demonstrated that
the 1-VR of five fatty acids between the reference value of the modeling sample
set and the near infrared spectrum predictive value were 0.8839, 0.5830, 0.9001,
0.9776 and 0.9596, respectively. And the SECV of five fatty acids between the
reference value of the modeling sample set and the near infrared spectrum
predictive value were 0.42, 0.29, 0.83, 0.46 and 0.21, respectively. The standard
error of the calibration (SECV) of five fatty acids between the reference value
of testing sample set and the near infrared spectrum predictive value were 0.891,
0.790, 0.900, 0.976 and 0.942, respectively. It was proved that the near infrared
spectrum predictive value was linear with chemical value and the mathematical
model established for fatty acids of soybean oil was feasible. For validation, 10
unknown samples were selected for analysis by near infrared spectrum. The result
demonstrated that the relative standard deviation between predict value and
chemical value was less than 5.50%. That was to say that transmission reflection
near infrared spectroscopy had a good veracity in analysis of fatty acids of
soybean oil.
PMID- 23156761
TI - [Infrared spectroscopic analysis of Guilin watermelon frost products].
AB - The objective of the present study is to analyze different products of Guilin
watermelon frost by Fourier transform infrared spectroscopy (FTIR), second
derivative infrared spectroscopy and two-dimensional correlation spectroscopy (2D
IR) under thermal perturbation. The structural information of the samples
indicates that samples from the same factory but of different brands had some
dissimilarities in the IR spectra, and the type and content of accessories of
them were different compared with conventional IR spectra of samples, peaks at
638 and 616 cm(-1) all arise from anhydrous sodium sulfate in watermelon frost
spray and watermelon frost capsule; the characteristic absorption peaks of the
sucrose, dextrin or other accessories can be seen clearly in the spectra of
watermelon frost throat-clearing buccal tablets, watermelon frost throat tablets
and watermelon frost lozenge. And the IR spectra of watermelon frost lozenge is
very similar to the IR spectra of sucrose, so it can be easily proved that the
content of sucrose in watermelon frost lozenge is high. In the 2D-IR correlation
spectra, the samples presented the differences in the position, number and
relative intensity of autopeaks and correlation peak clusters. Consequently, the
macroscopical fingerprint characters of FTIR, second derivative infrared spectra
and 2D-IR spectra can not only provide the information about main chemical
constituents in medical materials, but also analyze and identify the type and
content of accessories in Guilin watermelon frost. In conclusion, the multi-steps
IR macro-fingerprint method is rapid, effective, visual and accurate for
pharmaceutical research.
PMID- 23156762
TI - [Noninvasive measurement of serum total protein content by near-infrared
reflection spectra with tongue inspection].
AB - The technology of tongue near-infrared reflectance spectra was used for human
serum total protein (TP) content of noninvasive testing for the first time.
Reflectance spectrum on the tongue tips of 58 volunteers was collected, and the
biochemical values of serum total protein were recorded at the same time. The
samples were separated into two parts: training set and prediction set. Two
prediction models were established using PCA combined with BP neural network and
PLS. Using PCA-BP model to predict the prediction set, the average relative error
is 7.35%, RMSEP was 6.3771 g x L(-1), and the correlation coefficient was 0.9021.
Using PLS model to predict the prediction set, the average relative error is
4.77%, RMSEP was 0.1304 g x L(-1), and the correlation coefficient was 0.9718. It
was approved that reflectance spectra of tongue can be used to predict TP
accurately and noninvasively.
PMID- 23156763
TI - [Measuring soil water content by using near infrared spectral characteristics of
soil].
AB - Different textured soils (sandy loam, silty clay loam and clay) from Manas
County, Xinjiang were researched with indoor spectral reflectance, continuum
removal was used to process soil spectra curve, and correlation analysis was made
about normalized spectral reflectance and water content for modeling. The results
show that different textured soils have reflectance in a order that clay>silty
clay loam>sandy loam; the critical points of field capacity in sandy loam, silty
clay loam and clay were 20.01%, 24.10% and 30.43% respectively, and water content
was inversely proportional to spectral reflectance below such critical points
while proportional above the points. Within 1390-1623 nm band, the negative
correlation coefficients of soil water content and normalized spectra reflectance
show better negative correlation and reaching significant levels, R2 of the model
established for soil water content prediction exceeded mostly 0.8, and the
average relative error of the model was 10%. The model could accurately reflect
the soil moisture content, Its advantages such as accuracy, non-destruction and
rapidness provide a new approach to measuring soil water content.
PMID- 23156764
TI - [Sugar characterization of mini-watermelon and rapid sugar determination by near
infrared diffuse reflectance spectroscopy].
AB - In the present paper, the distribution of sugar level within the mini-watermelon
was studied, a new sugar characterization method of mini-watermelon using average
sugar level, the highest sugar level and the lowest sugar level index is
proposed. Feasibility of nondestructive determination of mini-watermenlon sugar
level using diffuse reflectance spectroscopy information was investigated by an
experiment. PLS models for measuring the 3 sugar levels were established. The
results obtained by near infrared spectroscopy agreed with that of the new method
established above.
PMID- 23156765
TI - [Study on rapid non-destructive detection of the freshness of paddy based on
NIRS].
AB - A prediction model of paddy storage time was established based on near infrared
reflectance (NIRS) and chemometrics. A spectroradiometer was used for collecting
spectra in the wavelength range from 950 to 1 650 nm. The NIR spectra were
collected from 90 samples of paddy. The best pretreatment method was obtained
while choosing the total spectra area combined with PLS using the UNSCRAMBLER
9.7. The best pretreatment method is first derivative combined with S. Golay, and
the number of principal components is 7. The model is feasible, because the r2 is
0.9679, RMSEP is 54.51 and the result of T-test is passable while validation
method is cross validation In this paper, a feasible method is established to
measure the storage time of paddy based on near infrared reflectance(NIRS)and
chemometrics.
PMID- 23156766
TI - [Similar spectrum of infrared spectrum and its application in identification of
Chinese herbs].
AB - In the present paper, the similar spectra of 18 samples, which include
Astragalus, red-blue Astragalus and Codonopsis, were obtained in the range of
1600-700 cm(-1). The result showed that all kinds of herbs have their own
characteristic similar spectra, and 18 samples can be identified according to the
characteristic similar spectra. Furthermore, three correlation coefficients of 93
ganoderma samples were calculated which is in the range of 1560-1502, 1460-1421
and 1319-1260 cm(-1) according to the information of similar spectrum of infrared
spectrum of ganoderma. Without priori knowledge of the classification of these
samples, the K-means cluster analysis can successfully divide them into four
classes, i.e., Ganoderma lucidum and Ganoderma sinensis, Ganoderma atrum,
Ganoderma aoshiba, Ganoderma multiplicatum. This result is consistent with the
result of morphological classification.
PMID- 23156768
TI - [Raman spectroscopic investigation of hydrogen storage in nitrogen gas hydrates].
AB - Recently, hydrogen storage using clathrate hydrate as a medium has become a
hotspot of hydrogen storage research In the present paper, the laser Raman
spectroscopy was used to study the hydrogen storage in nitrogen hydrate. The
synthetic nitrogen hydrate was reacted with hydrogen gas under relatively mild
conditions (e.g., 15 MPa, -18 degrees C). The Raman spectra of the reaction
products show that the hydrogen molecules have enclathrated the cavities of the
nitrogen hydrate, with multiple hydrogen cage occupancies in the clathrate
cavities. The reaction time is an important factor affecting the hydrogen storage
in nitrogen hydrate. The experimental results suggest that nitrogen hydrates are
expected to be an effective media for hydrogen storage.
PMID- 23156767
TI - [Study on rapid quantitative analysis of the active ingredient in ABC
extinguishing agent and type identification of extinguishing agent powders using
near infrared spectroscopy].
AB - A new quantitative method to determine the NH4H2PO4 in ABC powder extinguishing
agent and to distinguish between ABC and BC powder extinguishing agents using
near infrared diffuse reflectance spectroscopy is proposed. A PLS calibration
model for the NH4H2PO4 content in extinguishing agent powder was established,
with RMSECV = 2.1, RMSEP = 2.4. An identification model for ABC and BC powder
extinguishing agents was built by SIMCA and the identification accuracy rate is
100%. This method, compared to the present standard method, has the
characteristics of rapidness and easy operation, whichis fit for the quantitative
analysis and type distinguishing of the fire products on site.
PMID- 23156769
TI - [Infrared and Raman spectra study on Tianhuang].
AB - The Tianhuang stones, from Shoushan in China, were studied by using X-ray powder
diffractometry (XRD), infrared (IR) spectroscopy and Raman spectroscopy to obtain
the spectra characterization. Wave numbers 3621, 3629 and 3631 cm(-1) in the IR
spectra and 3626, 3627 and 3632 cm(-1) in the Raman spectra are the
characteristic peaks of dickitic Tianhuang, nacritic Tianhuang and illitic
Tianhuang, respectively. Raman spectra assigned to OH are in good agreement with
the IR results at 3550 -3750 cm(-1). Dickitic Tianhuang includes ordered dickite
and disordered dickite. Compared with ordered dickite, the band assigned to OH3
of disordered dickite shifts to low-frequency by 8 cm(-1) and the relative
intensity becomes stronger. The disorder structure may relate to the high level
of Fe. The IR absorption spectra of nacritic Tianhuang superimposes strong peaks
of dickite, indicating that IR absorption bands of dickite are stronger than that
of nacrite at 3550-3750 cm(-1). The main mineral composition of illitic Tianhuang
is 2M(1), while illite Tianhuang contains a small amount of 1M. All these
characters provide a theoretical basis for the scientific identification of
Tianhuang.
PMID- 23156771
TI - [Raman spectroscopy analysis of carbon structural evolution of diesel particulate
matters with the treatment of nonthermal plasma].
AB - Original and nonthermal plasma treated particulate matters (PM) samples of a
diesel were obtained and characterized by Raman spectroscopy. A five-bands model
was adopted for Raman spectrum curve fitting. As parameters involving most
information about carbon structure, variation of FWHM of D1 band and D3 relative
intensity were analyzed. It was found that original PM presented higher graphical
structural order and lower chemical heterogeneity with the increase in the diesel
load. After the treatment of NTP, the graphical structural order and chemical
heterogeneity of PM kept at a relative stable level, affected very slightly by
diesel load. Meanwhile, the amount of molecular carbon in PM increased. Further
study for relation between structural evolution and chemical reactivity of PM
with chemical kinetics would make Raman spectroscopy of great promise to become
an important method for PM characterization, which could provide basis for more
effective removal.
PMID- 23156770
TI - [Self-assembled film of gold nanoparticles at a air/water interface used as a
SERS substrate to detect melamine].
AB - Self-assembled monolayer film of gold nanoparticles (55 nm) was formed at air
water interface by the driving force of wettability-shift of gold nanoparticles
from hydrophilic property to hydrophobic property when encapsulated with 1
dodecanethiol. SEM image shows that the structure of the surface is nearly
monolayer with closed arrays of uniform particle size when the film is
transferred onto Si wafer. The substrate can be used for SERS substrate to
realize semiquantitative analysis of melamine and the detection limit can reach l
x 10(-9) g x L(-1). This SERS substrate is of wide application, not only for
melamine but also for nonpolar molecule such as polycyclic aromatic hydrocarbons.
PMID- 23156772
TI - [Curve fitting based on genetic algorithms for quantitative resolution in
overlapped fluorescence spectra].
AB - The exponentially modified Gaussian (EMG) model-based genetic algorithm was used
as a fitness function for fitting fluorescence spectrogram. The method was
effective for solving the interference of fluorescent substance in the course of
the multi-component quantitative analysis. As an example, the interference of
endogenous fluorophores in different urines with the fluorescence of gatifloxacin
(GFLX) was examined. A good eradicating efficacy was achieved by using the
fitting fluorescence spectrogram. Under the optimized experimental conditions,
the good linear relationship between the fluorescence intensity and GFLX
concentration was obtained in the range of 0.06-3.5 microg x mL(-1) with a
correlation coefficient of 0.9994. The detection limit and recovery were 0.02
microg x mL(-1) and 99.2%-109.4%, respectively, with the relative standard
deviation from 1.3% to 2.7%. The proposed fitting fluorescence spectrometric
method was rapid, simple and highly sensitive for the determination of GFLX in
different human urine without preseparation. The recovery, selectivity,
linearity, precision and accuracy of the method are convenient for routine assays
and pharmacokinetic studies.
PMID- 23156773
TI - [Effects of PEMF on fluorescence spectra of rats serum].
AB - To investigate the relationship between the fluorescence spectra of serum and the
brain injury effect, the alteration of fluorescence emission in serum was
collected by fluotescence spectroscopy, the pathologic changes in the rat brain
were obvious by histopathology after exposure to PEMF. Sprague-Dawley male rats
were randomized into sham exposed and PEMFs exposed groups. After exposure to
PEMF (3.5 ns rising time, 14 ns pulse width, and amplitude up to 200 kV/400 kV at
1 Hz repetitive rate) at 0.5, 1, 3, 6 and 12 h, the expression of S100B and the
fluorescence spectra in serum were detected, the changes in brain morphology were
observed. The results showed that the fluorescence intensity of 400 kV groups
were higher than 200 kV groups at different time points after exposure to PEMF.
It suggests that the extent of brain injury was associated with the pulse
frequency. The trends of fluorescence spectra in serum coincide with the
expression of S100B and pathologic changes. It shows that fluorescence
spectroscopy could apply to analysis of the effect of brain injury after exposure
to PEMF.
PMID- 23156774
TI - [Interaction between latex microspheres and antibody proteins revealed by
fluorescence spectroscopy].
AB - Latex-antibody complexes were prepared by the method of covalent coupling and the
properties of the complexes were studied by fluorescence spectrophotometric
method for the purpose of revealing the interaction between latex microspheres
and antibody proteins. Analysis of intrinsic fluorescence spectra showed that
after being coupled with latex microspheres, the emission maximum of antibody
protein showed an obvious blue shift, the intensity of emission maximum decreased
significantly, the tertiary structure of antibody protein changed to some extent,
the interaction between latex microspheres and antibody proteins had a great
quenching effect on the intrinsic fluorescence spectra of antibody proteins, the
quenching effect was enhanced along with the increasing pH value and latex
concentration, and the quenching mechanism was static quenching. Results of
exogenous fluorescence spectra showed that the fluorescence intensity of emission
maximum was enhanced significantly after being coupled with latex microspheres,
the hydrophobicity of antibody protein was decreasing with the increase in the pH
values, however, due to the increasing latex concentration, the hydrophobicity
antibody protein was increasing.
PMID- 23156775
TI - [Studies on micelle behaviors of sophorolipid biosurfactant by steady-state
fluorescence probe method].
AB - The critical micelle concentration (CMC) of sophorolipid was determined by steady
state fluorescence probe method in which pyrene was used as fluorescence probe.
Meanwhile, the changes in the sophorolipid CMC were examined in the addition of
NaCl and aliphatic alcohol, respectively. The results showed that the CMC of
sophorolipid was 1.3 x 10(-4) mol x L(-1) and had a slight decrease as NaCl
concentration increased. However, the CMC of sophorolipid appeared to increase in
the presence of aliphatic alcohol. The aggregation numbers and the micelle size
of sophorolipid solution were investigated by fluorescence quenching and laser
light scattering method. The aggregation numbers were 4-8 with the concentrations
of sophorolipid in the range of 4 -8 CMC and the micelle mean diameter for
sophorolipid with the concentration of 6 CMC was about 90 nm. These experimental
results indicated that the micelle should be incompact.
PMID- 23156776
TI - [Ultraviolet absorption spectrum analysis and identification of medicinal plants
of Paris].
AB - Species of Paris are important medicinal plants of China. They possess
anticancer, hot alexipharmic, detumescence, acesodyne, and arrest blood and
remove blood stasis effects. They are the main raw material for several Chinese
patent drugs such as "Yunnan Baiyao", "Gong Xue Ning", "Re Du Qing" and "Ji De
Sheng Sheyaopian". The present paper, through optimizing the chloroform, absolute
ethyl alcohol and water extraction condition of Paris by orthogonal test L3(4)
(16), using mean value, smoothness and second differential methods on the
observed UV spectrum, to inspects the RSD of stability and repeatability of
different waveband. By SIMCA and the common and variant peak ratio dual index
sequence analysis method, it evaluated the quality and quantity of Paris. The
results showed that at the time of 50, 40 and 50 min, chloroform, absolute ethyl
alcohol and water had the highest extraction ratios. Within 20 h, the RSDs of
stability were 0.06-1.88, 0.05-2.42 and 0.03-0.35; the RSDs of accuracy were 0
1.48, 0.05-0.37 and 0.09-0.44; and the RSDs of repeatability were 0-1.23, 0.04
0.30 and 0.12-0.25 respectively. The qualitative analysis revealed large
differences between different Paris species and different areas. The quantitative
analysis indicated that the highest common peak ratio among the Paris samples was
80.00% and the lowest variant peak ratio was 6.25%. The method evaluated Paris of
different species and from different producing areas, and also quantitatively
assessed the arbitrary two samples, clarified the similarity between the species
and areas of Paris, which provided basis of distinguishing the real and false,
identification of variety and quality evaluation for Chinese herbal medicine.
PMID- 23156777
TI - [Study on the mechanism of liesegang pattern development during carbonating of
traditional sticky rice-lime mortar].
AB - Liesegang patterns in traditional sticky rice-lime mortar undergoing carbonation
were investigated by means of FTIR, XRD and SEM. Results indicate that well
developed Liesegang patterns only occur in the mortar prepared with aged lime and
sticky rice. The smaller Ca(OH)2 particle size in aged lime and the control of
the sticky rice for the crystallization of calcium carbonate lead to the small
pores in this mortar. These small pores can make Ca2+ and CO3(2-) highly
supersaturated, which explains the reason why Liesegang pattern developed in the
sticky rice-aged lime mortar. The formed metastable aragonite proves that
Liesegang pattern could be explained based on the post-nucleation theory.
PMID- 23156778
TI - [Study on a method for fast selecting feature wavelengths from the spectral
information of crop nitrogen].
AB - Research on a method for fast selecting feature wavelengths from the nitrogen
spectral information is necessary, which can determine the nitrogen content of
crops. Based on the uniformity of uniform design, the present paper proposed an
improved particle swarm optimization (PSO) method. The method can choose the
initial particle swarm uniformly and describe the optimization space well by
fewer sample points, which is helpful to avoiding the local optimum and
accelerate the convergence. Then, the method was applied to fast select the
nitrogen spectral wavelengths of soybean, cotton and maize. Calibration models
based on the partial least square (PLS) method and selected wavelengths were
constructed. The results illustrate that compared with the original wavelengths,
the number of selected wavelengths decreases about 93%, which means the
computation is simplified. Also, the precision of PLS prediction mode based on
the selected wavelengths improves by 34% at least, and the prediction ability of
calibration model increases greatly. Therefore, the proposed method is both
correct and effective.
PMID- 23156779
TI - [Study of spectrum drifting of primary colors and its impact on color rendering
properties].
AB - LEDs are currently used widely to display text, graphics and images in large
screens. With red, green and blue LEDs as three primary colors, color rendition
will be realized through color mixing. However, LEDs' spectrum will produce
drifts with the changes in the temperature environment. With the changes in the
driving current simulating changes in the temperature, the three primary color
LEDs' spectral drifts were tested, and the drift characteristics of the three
primary colors were obtained respectively. Based on the typical characteristics
of the LEDs and the differences between LEDs with different colors in composition
and molecular structure, the paper analyzed the reason for the spectrum drifts
and the drift characteristics of different color LEDs, and proposed the equations
of spectrum drifts. Putting the experimental data into the spectrum drift
equations, the paper analyzed the impacts of primary colors on the mixed color,
pointed out a way to reduce the chromatic aberration, and provided the theory for
engineering application of color LEDs.
PMID- 23156780
TI - [Improving component analysis ability of the complex mixed solutions by multi
dimensional diffuse transmittance spectrometry].
AB - The multi-dimensional diffuse transmittance spectrums were collected by the
traditional near-infrared transmittance method combined with a scanning device,
and then used for component analysis of the complex mixed solution. A xenon
light, an electric control translation stage and a spectrometer were gathered to
set up a device; Intralipid-20%, India-ink and C6H12O6 were used to prepare 225
kinds of complex mixed solutions; the diffuse transmittance spectrums were
measured at 20 points off the transmission center distributed from 0-5 mm
(interval 0.25 mm); the single and multi-point diffuse transmittance spectrums
were analyzed by partial least squares regression for modeling and prediction.
The results show that the modeling and prediction accuracy of the concentrations
of the intralipid-20% and India-ink increased with the growing of the
transmittance points, but the concentration of the C6H12O6 did not increase. It
is proved that the spectrums collected by different points can raise the signal
to noise radio of the strong absorption and scattering substance, and the signal
to noise radio of the weak absorption and scattering substance would be improved
by increasing the current system accuracy.
PMID- 23156781
TI - [Study of residue preservatives thiabendazole, o-phenylphenol and diphenyl in
fruits and vegetables by SPE-separation technology].
AB - The residue of thiabendazole, o-phenylphenol and diphenyl in vegetables and
fruits was detected by solid-phase extraction and ultraviolet-spectrophotometry.
Samples were extracted under basic conditions with petroleum ether: ethyl acetate
(2:1). The analytes were first enriched, purified and separated through a C18
solid-phase extraction column. Thiabendazole, o-phenylphenol and diphenyl in the
C18 solid-phase extraction column were eluted with 30% ethanol-acid solution (pH
2.5), 55% methanol -alkaline solution (pH 11.5) and 75% ethanol-acid solution (pH
2.5) respectively ,then detected by ultraviolet-spectrophotometry. The linear
ranges were from 1 to 10 microg x mL(-1) with a good linear relationship (r >
0.9998) for thiabendazole, o-phenylphenol and diphenyl. The recovery range was
from 72.1% to 103.5%, with the relative standard deviations between 1.2% and
7.7%. The limit of detection (S/N = 3) was 0.09 Mg x mL(-1) (TBZ), 0.5 microg x
mL(-1) (OPP) and 0.1 microg x mL(-1) (DP). The method was successfully applied to
residues of preservatives in fruits and vegetables. These results indicated that
this method is simple, rapid and sensitive for the simultaneous determination
requirements of residues in vegetables and fruits.
PMID- 23156782
TI - [Cool/Hot target effect of the water fog infrared stealth].
AB - Artificial spray fog will come into being cool target because of the strong
evaporation and convection but weak radiation heat flux, when it is used for
defence of infrared imaging guided missile. Also, when it is the contrary
condition, the water fog will come into being hot target. In order to open out
the phenomenon particularly, a math model which can account for the cool/hot
effect produced by water fog shielding the thermal radiation is established by
coupling the calculation of radiation transfer equation and energy conversation
equation, based on the Mie theory. This model is proved to be accurate in
comparison with the Monte-Carlo method and Lambert-Beer' law. The water fog is
seemed as absorbing, emitting and anisotropic scattering medium, and the medium
radiation, multiple scattering, target radiation flux, and environment influence
such as the conductivity, convection turbulent heat diffusion and evaporation is
calculated. The phenomenon of cool/hot target effect can be shown in detail with
this model.
PMID- 23156783
TI - [Preparation and characterization of modified kaolins and their photocatalytic
property].
AB - In order to develop the cheap and efficient photocatalysts, kaolins were modified
through calcination and acid leaching. In succession, the prepared samples were
characterized using thermal gravimetric-differential thermal analysis (TG-DTA),
scanning electron microscope (SEM) coupled with energy dispersive spectroscopy
(EDS), X-ray diffraction (XRD), ultraviolet-visible spectroscopy (UV-Vis) and BET
specific surface area measurements (BET). Methyl orange, used as a model
reactant, was degraded under UV light irradiation to evaluate the photocatalytic
activities of the prepared samples. From UV-Vis spectroscopy analyses, an obvious
increase in the red shift of the absorption edge was observed for the samples
treated with acid. The acid sites generated during the modification of kaolin
were determined through adsorbed pyridine analysis using infrared spectroscopy
(Py-IR). Kaolins modified using over 30% H2SO4 contained both Bronsted and Lewis
acid sites. Combining the results of photocatalytic experiment with the
conclusions of Py-IR and XRD, the acid properties of the prepared samples were
the main factors that affected their catalytic activity.
PMID- 23156784
TI - [Research on spectral response of CdSe quantum dots dopted polymer solar cell].
AB - In the present paper, bulk heterojunction polymer solar cells based on P3HT:PCBM
and P3HT:PCBM:QDs active layer were fabricated and measured respectively. The
experimental result showed that the addition of QDs can broaden the spectral
response and enhance photoinduced electron transfer. The conversion efficiency of
device with QDs is about 25% higher than that without QDs.
PMID- 23156785
TI - [MTCARI: A kind of vegetation index monitoring vegetation leaf chlorophyll
content based on hyperspectral remote sensing].
AB - The chlorophyll content of plant has relative correlation with photosynthetic
capacity and growth levels of plant. It affects the plant canopy spectra, so the
authors can use hyperspectral remote sensing to monitor chlorophyll content. By
analyzing existing mature vegetation index model, the present research pointed
out that the TCARI model has deficiencies, and then tried to improve the model.
Then using the PROSPECT+SAIL model to simulate the canopy spectral under
different levels of chlorophyll content and leaf area index (LAI), the related
constant factor has been calculated. The research finally got modified
transformed chlorophyll absorption ratio index (MTCARI). And then this research
used optimized soil background adjust index (OSAVI) to improve the model. Using
the measured data for test and verification, the model has good reliability.
PMID- 23156786
TI - [Geometric distortion correction for hyperspectral image using a rotating scan
reflector].
AB - Offner imaging spectrometer is a kind of pushbroom imaging system. Hyperspectral
images acquired by Offner imaging spectrometers require relative motion of sensor
and scene that is translation or rotation. Via rotating scan with a reflector at
the front of sensor's len, large objects can be entirely captured. But for the
changes in object distances, geometric distortion occurs. A formula of space
projection from an object point to an image point by one capture was derived.
According to the projection relation and slit's motion curve, the object points'
coordinates on a reference plan were obtained with rotation angle for a variable.
A rotating scan device using a reflector was designed and installed on an Offner
imaging spectrometer. Clear images were achieved from the processing of
correction algorithm.
PMID- 23156787
TI - [Detection of activity of POD in tomato leaves based on hyperspectral imaging
technology].
AB - Activities of POD in tomato leaves were measured rapidly using hyperspectral
imaging technology combined with chemometrics method. Operation process was:
extracting spectra curve, pretreatment of spectra data, extracting characteristic
wavelengths with SPA, and establishing prediction model for determining POD
activities. In comparison with other methods such as SG, SNV, MSC, 1-Der and 2
Der, DOSC was the optimal pretreatment. It was shown in this research that SPA
PLS model was the optimal effective model among all models (SPA-MLR, SPA-PLS, SPA
BPNN and SPA-LS-SVM) for forecasting POD activities. The model was based on
reflectance information of effective wavelengths (443, 464, 413, 410, 401, 402,
426 and 926 nm) extracted by SPA. Rp and RMSEP were 0.9353 and 37.80 U x g(-1),
respectively. The result indicated that it was feasible to determine the POD
activities with hyperspectral imaging technology, and the prediction accuracy of
model was satisfactory. It was a new method for dynamic observation of POD
activities and growth state of tomato.
PMID- 23156788
TI - [Research of heavy metals determination in cereals by inductively coupled plasma
mass spectrometry].
AB - The present paper established the determination method of heavy metals such as
As, Pb, Hg and Cd in cereals by inductively coupled plasma mass spectrometry (ICP
MS) with microwave digestion. The pretreatment conditions were improved and the
instrument operating parameters were optimized. 72Ge, 115In and 209Bi were
selected as the internal standard elements to overcome the matrix effects and
instrument fluctuations effectively. Interference correction equations were used
to eliminate the interference of polyatomic ions. Satisfactory linearity of
standard curves was obtained with elemental correlation coefficients over 0.9999.
The detection limits were in the range of 0.0006-0.016 mg x L(-1), the recoveries
of samples were 90%-110%, and the RSD was within 5%. The accuracy of the method
was evaluated with national standard reference materials and the interference
test was experimented using standard solution. Studies have shown that the method
is suitable for rapid determination of heavy metals As, Pb, Hg and Cd in cereals
with wide linear range, good precision and high accuracy.
PMID- 23156789
TI - [Variation in soil Mn fractions as affected by long-term manure amendment using
atomic absorption spectrophotometer in a typical grassland of inner Mongolia].
AB - The effect of sheep manure amendment on soil manganese fractions was conducted in
a 11 year experiment at inner Mongolia grassland, using sequential extraction
procedure in modified Community Bureau of Reference, and determined by atomic
absorption spectrophotometer. Five treatments with dry sheep manure addition rate
0, 50, 250, 750, and 1500 g x m(-2) x yr(-1), respectively, were carried out in
this experiment. Results showed that the recovery rate for total Mn was 91.4%
105.9%, as the percentage recovered from the summation of the improved BCR
results with aqua regia extractable contents, and it was 97.2%-102.9% from
certified soil reference materials. Plant available exchangeable Mn could be
enhanced by 47.89%, but reducible and total Mn contents decreased significantly
under heavy application of manure at depth of 0-5 cm. The effect of manure
amendment on Mn fractions was greater in 0-5 cm than in 5-10 cm soil layer. The
results are benefit to micronutrient fractions determination and nutrient
management in grassland soils.
PMID- 23156790
TI - [Determination of soil exchangeable base cations by using atomic absorption
spectrophotometer and extraction with ammonium acetate].
AB - A method to determine soil exchangeable calcium (Ca), magnesium (Mg), potassium
(K), and sodium (Na) by using atomic absorption spectrophotometer (AAS) and
extraction with ammonium acetate was developed. Results showed that the accuracy
of exchangeable base cation data with AAS method fits well with the national
standard referential soil data. The relative errors for parallel samples of
exchangeable Ca and Mg with 66 pair samples ranged from 0.02%-3.14% and 0.06%
4.06%, and averaged to be 1.22% and 1.25%, respectively. The relative errors for
exchangeable K and Na with AAS and flame photometer (FP) ranged from 0.06%-8.39%
and 0.06-1.54, and averaged to be 3.72% and 0.56%, respectively. A case study
showed that the determination method for exchangeable base cations by using AAS
was proven to be reliable and trustable, which could reflect the real situation
of soil cation exchange properties in farmlands.
PMID- 23156791
TI - [Infrared spectroscopy and XRD studies of coral fossils].
AB - Coral fossil is an old remain of multicellular animal on the earth, and formed by
various geological processes. The structural characteristics and compositions of
the coral fossils with different color and radial texture on the surface were
studied by infrared absorption spectroscopy and X-ray powder diffraction
analyses. The results show that the studied coral fossils mainly are composed of
SiO2, and the radial microstructure characterized by the calcareous coral cross
section is preserved. It is formed by metasomatism by SiO2. The infrared
absorption spectra of the coral fossil with different color and texture are
essentially the same, showing typical infrared absorption spectra of the quartz
jade. XRD analysis shows that the main components of the coral fossils with
different color and texture are consistent and mainly composed of SiO2 with a
trace amount of other minerals and without CaCO3.
PMID- 23156792
TI - [Determination of 16 elements in the different pine pollen by TXRF].
AB - After microwave digestion, 16 elements in pine pollen were simultaneously
determined by TXRF. The results show that all the 16 elements were found in all
pine pollens. There was a significant difference in the average content of the
element such as Ca, Ti, Mn, Zn and Rb between different groups of pine pollen (P
< or = 0.01). There was a difference in the average content of the element such
as K, V, Fe, Co, Cu and Sr between them (P < or = 0.05). And there was no
difference in the average content of the element such as Cr, Ni, As, Pb and Se
between them. The results also show that pine pollen has the spectral
characteristics of warm property or cold property drug. They were closely related
to the tree species and the growth environment or the growth area.
PMID- 23156793
TI - [Chemical composition and chromaticity characteristic of Jilan glaze of Ming and
Qing official kilns].
AB - Color glazes of Ming and Qing official kilns are excellent representatives of the
famous ancient Chinese porcelains. The study of official ware with Jilan glaze
has been an important topic. But it made slow progress due to the rarity of
samples with strict production management and using system. The recipes, chemical
composition and chromaticity characteristic of the Jilan samples excavated from
official kilns in the Ming and Qing dynasties were first discussed by
systematical testing with the energy dispersive X-ray fluorescence (EDXRF) and
color difference meter. The results showed that the porcelain stone content in
Jilan bodies of official kiln in the Ming dynasty is higher than the samples of
the Qing dynasty. The manganese content in Jilan glazes of the Ming dynasty is
higher than that in the Qing dynasty, while the glaze ash addition and the
lightness value in the glaze are opposite.
PMID- 23156794
TI - [An automated method to fit stellar continuum based on statistic windows].
AB - A novel statistic window based method to fit stellar continuum is proposed. First
a stellar spectrum is divided into a series of statistic windows in which a
certain percent of flux points is selected according to S/N ratio; then low order
polynomial iteration fitting is carried out based on the selected flux points to
obtain the stellar continuum. Experimental results show that the continuum
obtained by the proposed method is more close to the real continuum, compared to
other existed methods. This method has a better practical applicability and
robustness to all kinds of spectra (except M-type spectrum) in SDSS. It also
works well for Guoshoujing Telescope (LAMOST) pilot survey spectra.
PMID- 23156795
TI - [Lossless compression of hyperspectral image for space-borne application].
AB - In order to resolve the difficulty in hardware implementation, lower compression
ratio and time consuming for the whole hyperspectral image lossless compression
algorithm based on the prediction, transform, vector quantization and their
combination, a hyperspectral image lossless compression algorithm for space-borne
application was proposed in the present paper. Firstly, intra-band prediction is
used only for the first image along the spectral line using a median predictor.
And inter- band prediction is applied to other band images. A two-step and
bidirectional prediction algorithm is proposed for the inter-band prediction. In
the first step prediction, a bidirectional and second order predictor proposed is
used to obtain a prediction reference value. And a improved LUT prediction
algorithm proposed is used to obtain four values of LUT prediction. Then the
final prediction is obtained through comparison between them and the prediction
reference. Finally, the verification experiments for the compression algorithm
proposed using compression system test equipment of XX-X space hyperspectral
camera were carried out. The experiment results showed that compression system
can be fast and stable work. The average compression ratio reached 3.05 bpp.
Compared with traditional approaches, the proposed method could improve the
average compression ratio by 0.14-2.94 bpp. They effectively improve the lossless
compression ratio and solve the difficulty of hardware implementation of the
whole wavelet-based compression scheme.
PMID- 23156796
TI - [EUV flat field grating spectrometer and performance measurement].
AB - A high-resolution extreme ultraviolet (EUV) spectrometer has been developed to
diagnose the magnetically confined plasmas. A holographic spherical varied line
spacing concave grating which provides a flat focal plane is used as the
diffraction element working with the grazing incidence angle of 3 degrees. The
nominal groove density is 1200 lines x mm(-1). A deeply cooled back-illuminated
CCD camera is used as the spectra detector and a mechanical shutter is used to
control the time of exposure. It covers the wavelength range of 5-50 nm with the
CCD cameral moving along the spectra focal plane to cover different wavelength
range interested. Spectrometer design is presented and it was tested by a Penning
discharge light source. By the wavelength calibration, the actual parameters of
the optical system were calculated and the wavelength accuracy is 0.003 nm.
Results show that the spectral resolution is about 0.015 nm at 20 nm with the
width of entrance slit opened at 30 microm, which agrees with the design goal.
PMID- 23156797
TI - [Design and implementation of real-time processing platform for movement error
correction of hyperspectrual imaging].
AB - The approach that deals with compressed and packed image data transmitted from
satellite to the ground is too slow for real-time application occasion, it also
has huge image, multi-processing step and complexity recovery arithmetic
synchronously, so it is urgent to build accurate and fast data processing
platform for real-time processing. For the moment, the platform for data recovery
and error correction is much less, the so-called successful platform may directly
affect the effect of target detection and identification because of processing
speed, precision, flexibility, configuration and upgrade. The platform we build
is to set spatial modulation spectrometer as the research goal, We design and
implement a hardware platform based on Xilinx Virtex-5 FPGA, It is combined with
ISE IP soft-core resources which is configurable, high-precision and flexible by
focusing on analyzing key aspects of the hardware platform. And the relevant test
data were drawn, then a good way for spectrum recovery and error correction was
explored.
PMID- 23156798
TI - [A method of precise adjustment and calibration for high-resolution echelle
spectrograph].
AB - Echelle spectrograph is a new type of high-resolution, high-precise spectrograph,
and its resolution can be up to tens of thousands to hundreds of thousands. In
this case, a little error of the structure will affect the resolution and
precision greatly, so an accurate adjustment is of importance for the echelle
spectrograph. According to the design features, the present paper discusses the
adjustment method for echelle spectrograph. This is an uncomplicated, quick
method, and adapts to mini, airproof structure of echelle spectrograph. Using
this method, the actual state is consistent with the design result. The result of
wavelength calibration is given out, and the error is less than 0.002 nm, which
satisfies the requirement of the system.
PMID- 23156799
TI - [The effects of signal to noise ratio of instrument and number of wavelengths on
the accuracy of spectral analysis].
AB - In order to study the influence of the two factors, the signal to noise ratio
(SNR) of instrument and number of wavelengths, on the accuracy of quantitative
analysis in spectral modeling analysis, the influences of different SNRs, the
number of wavelengths participating in partial least square regression, and multi
wavelength modeling in different SNR bands were taken into account. The
relationships between these factors and quantitative analysis accuracy were
explored by modeling analysis experiments. The results show that the analysis
accuracy is directly related to the SNR of instrument. And increasing
wavelengths, especial the ones with high SNR, reflects a phenomenon that four
times of wavelength number will bring 2 times accuracy increasing, which can
compensate for the lack of SNR. The research provides the experimental basis and
theoretical guidance to improve the model's quality and reduce the prediction
error by the utilization and improvement of the instrument's SNR and the
reasonable choice of wavelengths and bands of modeling.
PMID- 23156800
TI - [The analysis for improving the SNR of blood components noninvasive measurement
with DS method].
AB - In order to increase the accuracy of blood components measurement and enhance the
stability of prediction model, the quantitative signal-noise-ratio (SNR) analysis
of measuring instruments based on dynamic spectrum (DS) and preprocessing method
was conducted. The SNR of DS is increased after adding boxcar integrator,
decreasing wavelength revolution, balancing the DS's SNR and excluding gross
errors in preprocessing according to experiment results. Two volunteers were
tested continuously for many times using the DS data acquiring system. The
correlation coefficients of the each volunteer's DS data was increased from 0.934
and 0.953 to 0.991 and 0.987, respectively. Moreover, the gap between the
correlation coefficient of the same volunteer's DS and different volunteers' DS
is increased too, which shows that the SNR can be improved by these methods. The
quantitative SNR analysis can guide the way of choosing preprocessing method
efficiently, which will create the condition for clinical application of the
blood components noninvasive measurement.
PMID- 23156801
TI - [Motion control of moving mirror based on fixed-mirror adjustment in FTIR
spectrometer].
AB - The performance of the uniform motion of the moving mirror, which is the only
constant motion part in FTIR spectrometer, and the performance of the alignment
of the fixed mirror play a key role in FTIR spectrometer, and affect the
interference effect and the quality of the spectrogram and may restrict the
precision and resolution of the instrument directly. The present article focuses
on the research on the uniform motion of the moving mirror and the alignment of
the fixed mirror. In order to improve the FTIR spectrometer, the maglev support
system was designed for the moving mirror and the phase detection technology was
adopted to adjust the tilt angle between the moving mirror and the fixed mirror.
This paper also introduces an improved fuzzy PID control algorithm to get the
accurate speed of the moving mirror and realize the control strategy from both
hardware design and algorithm. The results show that the development of the
moving mirror motion control system gets sufficient accuracy and real-time, which
can ensure the uniform motion of the moving mirror and the alignment of the fixed
mirror.
PMID- 23156802
TI - [Detection of sorbic acid in food by homemade micro-spectrometer analytical
system].
AB - A homemade micro-spectrometer analytical system was developed for the
quantitative determination of the sorbic acid in the food based on the
photometric principle. And with the standard addition method it was applied to
eliminate the interference coming from the food substrate. The detecting result
illustrated a good relativity in the range of 0-10.0 mg x L(-1) with the linear
correlation coefficient of 0.9989, and the sample recovery was 99.2%-99.5% with
RSD of 0.58%. The micro-spectrometer analysis system has shown potential
prospective application in the fields of rapid and high performance detection for
food additives.
PMID- 23156803
TI - [Clinical examination of olfactory and gustatory function].
AB - OBJECTIVE: To explore changes of olfactory and gustatory functions in patients
with olfactory dysfunction. METHOD: The 284 study subjects included 92 healthy
volunteers, 92 with hyposmia and 100 with functional anosmia. Their olfactory and
gustatory functions were examined using T&T olfactometer, olfactory event-related
potentials (OERPs) and triple drop method, respectively. RESULT: The T&T results
showed that the difference between patients with hyposmia and functional anosmia
and healthy subjects had statistical significance. The OERPs results showed that
patients with olfactory dysfunction had N1 and P2 waves of prolonged latency and
reduced amplitude when compared to healthy subjects with the difference of
statistical significance. When compared to healthy subjects, patients with
olfactory dysfunction had clear hypogeusia and the difference had statistical
significance. There was no significant difference between female and male groups.
CONCLUSION: It is suggested that the apparently concomitant hypogeusia is in
patients with olfactory dysfunction. Decreased of olfactory and gustatory
function exhibited little or no relationship with gender. Combined examinations
of OERPs, T&T and triple drop method, could make it possible to reflect the
overall chemical sensory functions in subjects systematically and provide
scientific evidence for clinical diagnosis and treatment early.
PMID- 23156804
TI - [Expression of fascin and correlation with MVD in sinonasal inverted papilloma].
AB - OBJECTIVE: To investigate the expression of Fascin in sinonasal inverted
papilloma (SNIP) and the relationship between Fascin expression and microvessel
density (MVD). METHOD: The expression of Fascin and CD34 were determined by
immunohistochemistry in 30 cases of SNIP, 12 cases of nasal squamous cell
carcinoma (NSCC) and 10 cases of normal inferior turbinate (IT) tissues.
Meanwhile, CD34, measure of MVD, was counted at the same time. RESULT: Fascin was
expressed in 17 of 30 (56.6%) cases of SNIP, 10 of 12 (83.3%) cases of NSCC and 2
of 10 (20.0%) cases of normal IT tissues. Expression of Fascin was significantly
increased in SNIP and NSCC compared to normal tissues (P < 0.01). MVD counts was
23.64 +/- 2.74, 45.10 +/- 5.45, 74.76 +/- 7.32, respectively (P < 0.01). There
was a positive correlation between the expression of Fascin and MVD counts.
CONCLUSION: The high expression of Fascin and angiogenesis are significantly
associated with biological behaviour of SNIP. Fascin may play an important role
in the pathogenesis of SNIP and NSCC and synergic role with angiogenesis in
progression of SNIP.
PMID- 23156805
TI - [The expression and significance of smac, XIAP, caspase-3 in nonnasal inverted
papilloma].
AB - OBJECTIVE: To explore the expression and significance of second mitochondria
derived activator of caspase (Smac), X-linked inhibitor of apoptosis protein
(XIAP)and cysteine containing aspartate specific protease 3 (caspase-3) in the
growth, development and carcinogenesis of the nonnasal inverted papilloma (NIP).
METHOD: Immunohistochemical method was used to detect the expression of Smac,
XIAP, caspase-3 in 10 cases of nasal cavity mucosae (NM) and 45 cases of NIP, the
group of NIP including 25 cases of NIP without dysplasia, 11 cases of NIP with
dysplasia, and 9 cases of NIP with malignant transformation to squamous cell
carcinoma (SCC). RESULT: The intensity of the positive expression of Smac,
Caspase-3 in NIP were lower than NM, the intensity of the positive expression
decreased with the decreasing degree of histological differentiation. There was a
significant difference between NIP without dysplasia and SCC. It was presented
with a progressive tendency for the expression of XIAP in the group of NM and
NIP. The lower degree of histological differentiation, the higher intensity of
the positive expression. The expression between NIP without dysplasia and SCC had
a significant difference. Smac negatively correlated with XIAP (r(s) = -0.323, P
< 0.05), XIAP negatively correlated with caspase-3 (r(s) = -0.408, P < 0.01),
Smac positively correlated with caspase 3 (r(s) = 0.424, P < 0.01). CONCLUSION:
Smac, XIAP, caspase 3 might be associated with the growth and carcinogenesis of
NIP.
PMID- 23156806
TI - [The anatomy research of expanding vision of endoscopic maxillary sinus
operation].
AB - OBJECTIVE: To get the anatomical method of expanding vision of endoscopic
maxillary sinus operation to providing guidance for the satisfactory surgical
vision by measurement of nasal cavity and maxillary sinus relative structure.
METHOD: By anatomical measurement from 30 human cranium preparations (21 male, 9
female), which were marinated by 10% formaldehyde solution, we tried to find out
anatomical factors that influence expanding vision of endoscopic maxillary sinus
operation. RESULT: Measurement of cranium preparations: respective distance
between bone nasolacrimal canal anterior wall superior extremity, central
extremity, bottom extremity and borderline of maxillary sinus anterior wall and
medial wall were 0 mm, (1.90 +/- l.03) mm, (3.29 +/- 1.04) mm. Distance between
anterior inferior part of bone nasolacrimal canal and anterior edge of inferior
concha was (5.13 +/- 0.62) mm, and vertical distance between anterior inferior
part of bone nasolacrimal canal and nasal bottom was (16.89 +/- 0.97) mm. The
difference between right and left side had no significant statistic sense (P >
0.05). Removal of the bone area: the upper and lower diameter of part of the
inferior turbinate attachment was (9.43 +/- 1.72) mm, anteroposterior diameter
from top to bottom was (9.76 +/- 0.83) mm, (11.39 +/- 0.50) mm, (12.85 +/- 0.66)
mm, the upper and lower diameter of the following part of the inferior turbinate
attachment was (13.52 +/- 0.83) mm, anteroposterior diameter from top to bottom
was (19.89 +/- 1.37) mm, (16.59 +/- 0.77) mm, (12.48 +/- 0.91) mm. CONCLUSION:
Dissection from inferior turbinate anterior part approach to maxillary sinus
could expand the endoscopic operation vision.
PMID- 23156807
TI - [The effect of biyuanshu oral liquid on the formation of Pseudomonas aeruginosa
biofilms in vitro].
AB - OBJECTIVE: To observe the effect of biyuanshu oral liquid on the formation of
pseudomonas aeruginosa biofilms in vitro. METHOD: Pseudomonas aeruginosa biofilm
was established by plate culture and detected by Scanning electron microscopy and
AgNO3 staining. After treated with different dosages of biyuanshu oral liquid and
erythromycin, the pseudomonas aeruginosa biofilms were observed by AgNO3 staining
and the number of viable bacteria were measured by serial dilution. RESULT: The
pseudomonas aeruginosa biofilms could be detected by SEM at the seventh culture
day and it was consistent with the detection of AgNO3 staining. The biyuanshu
oral liquid and erythromycin have the effect on inhibiting the formation of
pseudomonas aeruginosa biofilms. But with the already formed pseudomonas
aeruginosa biofilms the inhibition was not significant. The serial dilution
method showed that the viable counts of bacteria of biyuanshu oral liquid and
erythromycin treated groups were significantly lower than those untreated groups
(P < 0.05). CONCLUSION: The biyuanshu oral liquid and erythromycin can inhibit
the formation of pseudomonas aeruginosa biofilms in vitro.
PMID- 23156808
TI - [Endoscopic endonasal surgery for cranial base tumor].
AB - OBJECTIVE: To explore the application of endoscopic endonasal approach in surgery
for skull base tumor. METHOD: From August 2000 to February 2009, retrospective
analyses were performed on clinical data of 21 patients with skull base lesions
treated by endoscopic endonasal surgery. There were 3 chordoma, 6 olfactory
neuroblastoma, 4 squamous cancer, 5 malignant melanoma, 1 mucoepidermoid
carcinoma, 2 sphenoidal malignant adenoma. RESULT: Total tumor removal was
obtained in 21 cases,subtotal removal in 2 cases. With follow up of 24 to 108
months, 4 cases were recurred, 5 cases were dead. The complications included
cerebrospinal fluid (CSF) leak in 2 patients, intracranial infection after the
endoscopic surgery in 1 patient. In the two patients with CSF leak, one case
cured by internal medicine and another cured by endoscopic surgery. CONCLUSION:
The endoscopic endonasal surgery could provide sufficient treatment for skull
base tumor, and is a safe, minimally invasive and efficient procedure, but
indication should be exactitude selected.
PMID- 23156809
TI - [The study of risk factors of nasal septal perforation in rats].
AB - OBJECTIVE: To study the risk factors and interaction of nasal septal perforation
(NSP) in rats. METHOD: Animals (n=120) that underwent unilateral nasal
obstruction using Merocel nasal packing or gelfoam with/without standard
staphylococcus aureus inoculation were observed for the formation of NSP at 2, 3,
5, and 7 days after operation by endoscope system. Following sacrifice at 7 days,
the obtained nasal secretions were prepared for bacterial culture. Experimental
interventions were compared with normal controls (n=10). RESULT: Perforation of
nasal septum was observed in 80% of the animals accepted nasal obstruction using
Merocel nasal packing with standard staphylococcus aureus inoculation in 3 days
(P < 0.01), while in 70% of those using abacterial Merocel nasal packing in 5
days (P < 0.05) and no significant difference than that of before (P > 0.05).
There was a weak region in anteroinferior nasal septum in rats, which the almost
NSPs located in. The position of NSP does not overlap Merocel. CONCLUSION: The
interaction of risk factors contributes to NSP. The occurrence of NSP mainly
depends on the construction of nasal septum, while dysaemia is also necessary.
Obstruction of nasal drainage and infection promote the development of NSP.
PMID- 23156810
TI - [A longitudinal study of balance in migraineurs].
PMID- 23156811
TI - [A meta-analysis compare rapid rhino with merocel for nasal packing].
AB - OBJECTIVE: To assess the efficacy and adverse reaction of nasal packing materials
Rapid Rhino and Merocel. METHOD: We searched the database PubMed, EMBASE,
Cochrane Library, CBM, CNKI, VIP and WANFANG database on line by computer, and
traced the related references. Randomized controlled trials(RCTs) of rapid rhino
and merocel as nasal packing materials were included. The quality of the included
documents was evaluated by the criterion of Cochrane handbook 5.1. The cochrane
collaboration's Revman 5.1 software was used for data analysis. RESULT: Four RCTs
involving 115 patients were identified. Meta-analyses showed that Rapid Rhino
produced significantly lower pain and discomfort during insert of pack [MD =
1.37, 95% CI (0.13, 2.60), P < 0.05], whereas less pain and discomfort during
removal of pack [MD = 2.88, 95% CI (2.34, 3.41), P < 0.01]. Rapid Rhino
associated with a significantly slighter degree of fullness raised after
insertion [MD = 1.15, 95% CI (0.75, 1.55), P < 0.01, and the same situation
happened after 6 hours [MD = 1.15, 95% CI (0.75, 1.55), P < 0.01]. Rapid rhino
caused to less reactionary bleeding when pack removal [MD = 0.26, 95% CI (0.12,
0.39), P < 0.01], rapid rhino was easier for the healthcare worker during insert
and removal. There was no significant difference between two packs on the
efficiency of hemostatic [OR = 1.00, 95% CI (0.38, 2.61), P > 0.05]. CONCLUSION:
The application of Rapid Rhino caused less pain and fullness, leaded to slighter
bleed than Merocel when insertion and removal. There was no significant
difference between two packs on the efficiency of hemostatic when used for
epistaxis or after routine nasal surgery.
PMID- 23156812
TI - [Comparison the therapeutic effects of the comprehensive treatment of surgery
combined with radiotherapy and radiotherapy treatment only in laryngopharyngeal
carcinoma cases].
AB - OBJECTIVE: Comparing the difference between the effect of comprehensive treatment
and that of radiotherapy only in laryngopharyngeal carcinoma cases. METHOD:
Analyzing clinical data of 68 cases of laryngopharyngeal carcinoma treated in our
department from June 2003 to December 2009. Among them, 40 cases were treated by
comprehensive treatment of surgery combined with radiotherapy (group A), 28 cases
by radiotherapy only (group B). RESULT: The three-year survival rate of group A
and B were 75.6% (31/41) and 26.7% (4/15), respectively, and the five-year
survival rate of the two groups were 56.1% (23/41) and 13.3% (2/15),
respectively. CONCLUSION: For laryngopharyngeal carcinoma cases, the therapeutic
effect of comprehensive treatment was much better than that of the radiotherapy
only, not only could improve the survival rate, but also could make the life
quality after treatment better.
PMID- 23156813
TI - [Clinical investigation of 26 cases of fungal rhinosinusitis endoscopic surgery].
PMID- 23156814
TI - [Fifty two patients with chronic dacryocystitis treated by dacryocystorhinostomy
under endoscope and T drainage tube inserting].
PMID- 23156815
TI - [A report of the solitary fibrous tumor in nasal cavity].
AB - A 56-year-old woman, with a 1-day history of bilateral nose haemorrhagia,
predominantly on the right side, sometimes manifested rhinocnesmus, sneeze and
water rhinorrhea, no nose obstruction, and no fever. Endoscopy revealed a smooth
and pinkish mass that completely obstructed the right nasal cavity and extended
to the base of nose. Computed tomography showed a large mass that occupied the
entire right nasal cavity and part of the right maxillary sinus, ethmoidal sinus
and frontal sinusitis.
PMID- 23156816
TI - [Delayed abscess of nasal septum caused by bipolar coagulation treatment for
nosebleed: a case report].
AB - Clinical manifestation bipolar coagulation treatment for nosebleed. The patient
was affected by nasal obstruction, fever and headache three weeks after
operation. Clinical and laboratory examination nasal septum's bilateralism
knuckle, soft quality, puncture with purulent secretion. Diagnose: abscess of
nasal septum.
PMID- 23156817
TI - [Delayed abscess of nasal septum caused by bipolar coagulation treatment for
nosebleed: a case report].
AB - Clinical manifestation bipolar coagulation treatment for nosebleed. The patient
suffered from obstruction,fever and headache three weeks after operation.
Clinical and laboratory examination nasal septum bilateralism knuckle, soft
quality, puncture with purulent secretion. Diagnose: abscess of nasal septum.
PMID- 23156818
TI - [The research of intensity focused ultrasound on the treatment of allergic
rhinitis].
AB - Allergic rhinitis is a common disease in otorhinolaryngology, there are lots of
physiotherapies now, the overview of the research of intensity focused ultrasound
on the treatment of allergic rhinitis was mainly reviewed.
PMID- 23156819
TI - Doctors of interest. Recipients of suspect drug-company payments academic medical
centers, have drawing attention of federal fraud enforcers.
AB - As the federal government begins to focus more on wasteful healthcare spending,
doctors' relationships with drug companies are coming under scrutiny. Many times,
those relationships are legitimate, says Mary Riordan, left, a senior counsel to
HHS' inspector general's office. "There are other situations where the
relationship between the doctor and the manufacturer is suspect".
PMID- 23156820
TI - Ryan: plan is bipartisan. The 'time has come' for premium support, he says.
PMID- 23156821
TI - Bare necessities. Little state progress on defining coverage requirements.
PMID- 23156822
TI - Challenging the alternative. Rule targets advantage of some transplant systems.
PMID- 23156823
TI - Ups and downs. Investment portfolios see no returns in 2011.
PMID- 23156824
TI - Medicare, front and center. Ryan re-energized the debate; now it's time for
everyone to show their plans.
PMID- 23156825
TI - Reducing readmissions. Data system helps address complex questions, improve
medicine.
PMID- 23156826
TI - Supply-side economics. Purchasing practices at hospitals and health systems
continue to evolve, with the supply chain continuing to be a target for large non
labor cost savings.
PMID- 23156828
TI - Electronic medical records professional.
PMID- 23156827
TI - Evolving accreditation. Rise of ACOs prompts group to expand services beyond
ambulatory care.
PMID- 23156829
TI - Foreword: celebrating the first ten years of research excellence from the Jackson
Heart Study.
PMID- 23156830
TI - Foreword: applauding research efforts addressing disparities in cardiovascular
disease.
PMID- 23156831
TI - Foreword: a tribute to the work of JHS investigators, the Jackson community and
NIH scientists.
PMID- 23156832
TI - Introduction: Jackson Heart Study--building a 21st century platform for
discovery, service and training to address an American health priority.
PMID- 23156833
TI - Cardiovascular disease outcomes: priorities today, priorities tomorrow for
research and community health.
AB - The disparities and differences in heart disease and stroke among Black, White
and Hispanic populations tell a compelling and continuing story that should drive
research agendas to improve health outcomes. With Black men and women having the
highest prevalence of hypertension, Black females having higher rates of coronary
heart disease, stroke and breast cancer than White females, and Blacks, at all
ages, having a greater risk for stroke mortality than Whites, researchers and
health care providers must understand the clinical appropriateness of treatment
for different states of disease among distinct populations. Further, to eliminate
health disparities, the health care systems and legal regulatory climate must
facilitate access to care while biases, prejudices and stereotyping by health
care providers and all those in the health care system must be eliminated.
Importantly, research continues to illustrate that many are dying prematurely or
have advanced stages of disease because of disparate care. This article explores
four strategies to address inequitable care and to work toward eliminating poorer
health outcomes among minorities. First, those who deliver health care must adopt
a quality-focused approach that improves the care of all patients while
facilitating the reduction and elimination of health disparities. Second,
cultural awareness and cultural competency must be improved. Third, we must
remove barriers to access and promote public policies that lead to greater health
awareness and healthier environments. Lastly, but most importantly, we need a
prevention focus as the reduction in the onset of disease is the first step
towards improving health outcomes.
PMID- 23156834
TI - The social context of cardiovascular disease: challenges and opportunities for
the Jackson Heart Study.
AB - African Americans have higher rates of cardiovascular disease (CVD) than Whites
and the racial gap in heart disease is widening over time. There are especially
striking patterns of the earlier onset of disease, greater severity of illness
and large racial differences in CVD even when Blacks and Whites are compared at
the same level of economic status. This paper outlines critical research
opportunities for the Jackson Heart Study to advance the science base for
understanding and effectively addressing racial disparities in CVD. These
include: 1) the study of CVD by using a life course perspective; 2)
comprehensively characterizing social stressors; 3) expanding our analysis of how
racism affects health; 4) explicating variation in the levels and impact of risk
factors; 5) advancing our understanding of the contribution of genetics to CVD;
6) understanding resilience and its effects on CVD; and 7) identifying how
economic crises can shape CVD risk.
PMID- 23156835
TI - The revolution in risk assessment and disease detection made possible with non
invasive imaging: implications for population science.
AB - The ability to quantify subclinical disease to assess cardiovascular disease is
greatly enhanced by modern medical imaging techniques that incorporate concepts
from biomedical engineering and computer science. These techniques' numerical
results, known as quantitative phenotypes, can be used to help us better
understand both health and disease states. In this report, we describe our
efforts in using the latest imaging technologies to assess cardiovascular disease
risk by quantifying subclinical disease of participants in the Jackson Heart
Study. The CT and MRI exams of the Jackson Heart Study have collected detailed
information from approximately 3,000 participants. Analyses of the images from
these exams provide information on several measures including the amount of
plaque in the coronary arteries and the ability of the heart to pump blood. These
measures can then be added to the wealth of information on JHS participants to
understand how these conditions, as well as how clinical events, such as heart
attacks and heart failure, occur in African Americans.
PMID- 23156836
TI - The impact of traditional risk factor development on the life course of
cardiovascular diseases.
AB - This report discusses the profound impact of established risk factors for
coronary heart disease (CHD) and cardiovascular disease (CVD), from the
perspective of both shortterm and lifetime risks. Emerging data have confirmed
the major importance of aggregate risk factor burden in middle and older age on
remaining lifetime risks for CVD. The relatively new concept of the ideal
cardiovascular health factor profile will play a central role in plans to improve
the longevity, healthy longevity, and quality of life and health care costs of
all Americans. In this context, the agenda of the Jackson Heart Study should
promote understanding of and identify means for enhancing the roles of CVD
prevention and health promotion among African Americans.
PMID- 23156837
TI - CVD health factors and CVD risk factors: state of the science, emerging
priorities part 2: obesity prevention.
AB - This report outlines a course of action to prevent obesity and stall the obesity
epidemic now underway in the United States and other parts of the world. While
African Americans and Hispanics are most vulnerable to obesity, the etiology of
obesity shows that both genetic and environmental factors are responsible for
overweight and obesity. Although obesity is familial, genes may not be the main
culprit; and, in fact, explain < 20% of the obesity prevalence. Clearly,
environmental factors (specifically those related to energy intake [diet] and
energy output [physical activity]) are more often associated with obesity.
Patients with multiple risk factors, including obesity, for cardiovascular
disease need to be treated aggressively with lifestyle modifications and
medications, when necessary, to affect positive cardiovascular health outcomes.
However, a wiser, healthier approach to obesity is to prevent it from occurring
in the first place.
PMID- 23156838
TI - Genes and environments: moving toward personalized medicine in the context of
health disparities.
AB - Understanding gene-environment interactions that may influence disease is the
cornerstone of a personalized medicine approach built on diagnostics, risk
assessment/risk modification, pharmacogenetics and biology. Although genetic and
personalized medicine can influence clinical decision making, currently most
genetic information is based on populations of European ancestry. Additional
human genome research must include diverse populations in order to assess the
impact DNA sequence variation and environmental influences have on human disease
risk. Within this article, we present a brief overview of human genome variation
and discuss how epigenomics may influence gene expression. Examples of gene
environment interactions are explored and linked to several health disparities
and health outcomes among communities of color. With the Jackson Heart Study
poised to take the next steps in examining genes and the environment in ways that
other cohorts cannot, we will be closer to a more inclusive personalized medicine
goal that transforms medicine from curative to preemptive for all.
PMID- 23156839
TI - The Jackson Heart Study of the future.
PMID- 23156840
TI - Part 1. Biologic responses in rats and mice to subchronic inhalation of diesel
exhaust from U.S. 2007-compliant engines: report on 1-, 3-, and 12-month
exposures in the ACES bioassay.
AB - The Health Effects Institute and its partners conceived and funded a program to
characterize the emissions from heavy-duty diesel engines compliant with the 2007
and 2010 on-road emissions standards in the United States and to evaluate
indicators of lung toxicity in rats and mice exposed repeatedly to diesel exhaust
(DE*) from 2007-compliant engines. The preliminary hypothesis of this Advanced
Collaborative Emissions Study (ACES) was that 2007-compliant on-road diesel
emissions ". . . will not cause an increase in tumor formation or substantial
toxic effects in rats and mice at the highest concentration of exhaust that can
be used . . . although some biological effects may occur." This hypothesis is
being tested at the Lovelace Respiratory Research Institute (LRRI) by exposing
rats by chronic inhalation as a carcinogenicity bioassay, measuring indicators of
pulmonary toxicity in rats after 1, 3, 12, and 24-30 months of exposure (final
time point depends on the survival of animals), and measuring similar indicators
of pulmonary toxicity in mice after 1 and 3 months of exposure. This report
provides results of exposures through 3 months in rats and mice. Emissions from a
2007-compliant, 500-horsepower-class engine and aftertreatment system operated on
a variable-duty cycle were used to generate the animal inhalation test
atmospheres. Four treatment groups were exposed to one of three concentrations
(dilutions) of exhaust combined with crankcase emissions, or to clean air as a
negative control. Dilutions of exhaust were set to yield average integrated
concentrations of 4.2, 0.8, and 0.1 ppm nitrogen dioxide (NO2). Exposure
atmospheres were analyzed by daily measurements of key components and periodic
detailed physical-chemical characterizations. Exposures were conducted 16 hr/dy
(overnight), 5 dy/wk. Rats were evaluated for hematology, serum chemistry,
bronchoalveolar lavage (BAL), lung cell proliferation, and histopathology after 1
month of exposure, and the same indicators plus pulmonary function after 3
months. Mice were evaluated for BAL, lung cell proliferation, and respiratory
tract histopathology after 1 month of exposure, and the same indicators plus
hematology and serum chemistry after 3 months. Samples from both species were
collected for ancillary studies performed by investigators who were not at LRRI
and were funded separately. Exposures were accomplished as planned, with average
integrated exposure concentrations within 20% of the target dilutions. The major
components were the gaseous inorganic compounds, nitrogen monoxide (NO), NO2, and
carbon monoxide (CO). Minor components included low concentrations of diesel
particulate matter (DPM) and volatile and semivolatile organic compounds (VOCs
and SVOCs). There were no exposure-related differences in mortality or clinically
evident morbidity. Among the more than 100 biologic response variables evaluated,
the majority showed no significant difference from control as a result of
exposure to DE. There was evidence of early lung changes in the rats, accompanied
by a number of statistically significant increases in inflammatory and oxidative
stress indicators, and some evidence of subtle changes in pulmonary function. In
general, statistically significant effects were observed only at the highest
exposure level. The mice did not have the same responses as the rats, but did
have small but statistically significant increases in lavage neutrophils and the
cytokine IL-6 at 1 month (but not at 3 months). These findings suggest that the
rats were more sensitive than mice to the subchronic exposures.
PMID- 23156841
TI - Part 2. Assessment of genotoxicity after exposure to diesel exhaust from U.S.
2007-compliant diesel engines: report on 1- and 3-month exposures in the ACES
bioassay.
AB - Micronucleus (MN*) formation is a well-established endpoint in genetic
toxicology; studies designed to examine MN formation in vivo have been conducted
for decades. Conditions that cause double-strand breaks or disrupt the proper
segregation of chromosomes during division result in an increase in MN frequency.
Thus this endpoint is commonly employed in preclinical studies designed to assess
the potential risks of human exposure to a myriad of chemical and physical
agents, including inhaled diesel exhaust (DE). As part of the Advanced
Collaborative Emissions Study (ACES) this investigation examined the potential of
inhaled DE to induce chromosome damage in chronically exposed rodents. The ACES
design included exposure of both rats and mice to DE derived from 2007-compliant
heavy-duty engines. The exposure conditions consisted of air control and
dilutions of DE resulting in three levels of exposure. At specified times, blood
samples were collected, fixed, and shipped by the bioassay staff to Litron
Laboratories for further processing and analysis. Significant improvements have
been made to MN scoring by using objective, automated methods such as flow
cytometry, which allows for the detection of micronucleated reticulocytes (MN
RET), micronucleated normochromatic erythrocytes (MN-NCE), and reticulocytes
(RETs) in peripheral blood samples from mice and rats. By using a simple staining
procedure coupled with rapid and efficient analysis, many more cells were
examined in less time than was possible in traditional, microscopy-based MN
assays. Thus, for each sample, 20,000 RETs were scored for the presence of MN. In
the chronic-exposure bioassay, blood samples were obtained from independent
groups of exposed animals at specific time points throughout the course of the
entire study. This automated method is supported by numerous regulatory
guidelines and meets the requirements for an Organization of Economic Cooperation
and Development (OECD)-compliant assay for genotoxicity. Statistical approaches
employed analysis of variance (ANOVA) to compare effects of sex, exposure
condition, and duration, as well as their interactions. This initial assessment
of MN was performed on both mouse and rat blood samples from the 1-month and 3
month exposures. The data from mice demonstrate the well established, sex-based
difference in MN-RET and MN-NCE frequencies regularly observed in this species,
with females exhibiting slightly lower frequencies. There were no sex-based
differences observed in rats. An examination of the mean frequencies across the
exposure groups and durations of exposure did not show an appreciable induction
of MN at the 1- or 3-month exposures in either species. Further statistical
analyses did not reveal any significant exposure-related effects. An examination
of the potential genotoxic effects of DE is clearly valuable as part of a large
scale chronic-exposure bioassay. The data and observations from the 1-and 3-month
exposure studies will eventually be combined with the results from the 1- and 2
year exposure studies to provide a comprehensive examination of chronic exposure
to DE in a rodent model. This examination of chromosome damage serves an
important role in the context of the entire ACES bioassay, which was designed to
assess the safety of diesel combustion engines.
PMID- 23156842
TI - Part 3. Assessment of genotoxicity and oxidative stress after exposure to diesel
exhaust from U.S. 2007-compliant diesel engines: report on 1- and 3-month
exposures in the ACES bioassay.
AB - Human health hazards due to diesel exhaust (DE*) exposure have been associated
with both solvent and combustion components. In the past, diesel engine exhaust
components have been linked to increased mutagenicity in cultures of Salmonella
typhimurium and mammalian cells (Tokiwa and Ohnishi 1986). In addition, DE has
been shown to increase both the incidence of tumors and the induction of 8
hydroxy-deoxyguanosine adducts (8-OHdG) in ICR mice (Ichinose et al. 1997).
Furthermore, DE is composed of a complex mixture of polycyclic aromatic
hydrocarbons (PAHs) and particulates. One such PAH, 3-nitrobenzanthrone (3-NBA),
has been identified in DE and found in urban air. 3-NBA has been observed to
induce micronucleus formation in DNA of human hepatoma cells (Lamy et al. 2004).
The purpose of the current research, which is part of the Advanced Collaborative
Emissions Study (ACES), a multidisciplinary program being carried out by the
Health Effects Institute and the Coordinating Research Council, is to determine
whether improvements in the engineering of heavy-duty diesel engines reduce the
oxidative stress and genotoxic risk associated with exposure to DE components. To
this end, the genotoxicity and oxidative stress of DE from an improved diesel
engine was evaluated in bioassays of tissues from Wistar Han rats and C57BL/6
mice exposed to DE. Genotoxicity was measured as strand breaks using an alkaline
modified comet assay. To correlate possible DNA damage found by the comet assay,
measurement of DNA-adduct formation was evaluated by a competitive enzyme-linked
immunosorbent assay (ELISA) to determine the levels of free 8-OHdG found in the
serum of the animals exposed to DE. 8-OHdG is a specific modified base indicating
an oxidative type of DNA damage to DNA nucleotides. In addition, a thiobarbituric
acid reactive substances (TBARS) assay was used to assess oxidative stress and
damage in the form of lipid peroxidation in the hippocampus region of the brains
of DE-exposed animals. Results from the comet assay showed no significant
differences in rats between the control and exposed groups (P = 0.53, low
exposure; P = 0.92, medium exposure; P = 0.77, high exposure) after 1 month of DE
exposure. There were no differences between sexes in the responses of rats to
these exposures. Likewise, there were no significant differences found after 3
months of exposure. Similarly, no significant differences were found between the
mice exposed for 1 and 3 months to DE, nor were any differences found between
sexes. Measurements of 8-OHdG in both mice and rats showed no significant
difference among DE exposure groups (P = 0.46, mice; P = 0.86, rats). In mice,
measured 8-OHdG was lower in the 3-month group than the 1-month group. In rats,
the inverse was true. In mice, no significant differences in the levels of lipid
peroxidation, as measured by TBARS, were found between the controls and DE
exposure groups (P = 0.92), nor were there any differences between sexes. In
rats, comparisons between the control and low-exposure groups approached
significance, but no significant differences were found between the other DE
exposure groups. Additionally, in rats, there were no significant differences
between the 1- and 3-month DE exposure groups.
PMID- 23156843
TI - Part 4. Effects of subchronic diesel engine emissions exposure on plasma markers
in rodents: report on 1- and 3-month exposures in the ACES bioassay.
AB - Although epidemiologic and experimental studies suggest that exposure to diesel
exhaust (DE*) emissions causes adverse cardiovascular effects, neither the
specific components of DE nor the mechanisms by which DE exposure could induce
cardiovascular dysfunction and exacerbate cardiovascular disease (CVD) are known.
Moreover, because the advance of new technologies has resulted in cleaner fuels
and decreased engine emissions, there is even more uncertainty about the
relationship between DE exposure and cardiovascular health effects. To address
this ever-changing baseline of engine emissions, we tested for exposure-, sex-
and duration-dependent alterations in plasma markers following subchronic
exposure of mice and rats to DE emissions from a 2007-compliant diesel engine.
Many plasma markers--several recognized as known human CVD risk factors--were
measured in the plasma of rodents exposed to 1 or 3 months of air (the control)
or DE emissions. Few changes in plasma markers resulted from exposure to DE,
although significant exposure-level-dependent increases in total cholesterol and
high-density lipoprotein (HDL) cholesterol were observed in male rats after 1
month of DE exposure, an effect that was neither sustained nor observed in any
other group. These data indicate that DE emissions from a 2007-compliant diesel
engine as tested in this study had little adverse effect on CVD markers in
rodents.
PMID- 23156844
TI - Immune system is an important system of the body for maintenance of health.
PMID- 23156845
TI - Staphylococcus aureus superantigens and their role in eosinophilic nasal polyp
disease.
AB - Nasal polyposis is a chronic disease of the upper airways which adversely affects
the quality of life of patients. Its pathophysiology is still unclear. Recently,
several studies have shown different inflammatory pathways which relate to both
innate and adaptive immune responses. Moreover, different phenotypes may exist in
different ethnic groups of patients. This article will review recent data
regarding the type of inflammation, cytokine profiles, involvement of macrophages
and dendritic cells, and the impact of various organisms (especially
Staphylococcus aureus and its superantigens) and their association with lower
airway disease (especially asthma).
PMID- 23156846
TI - A double-masked comparison of 0.1% tacrolimus ointment and 2% cyclosporine eye
drops in the treatment of vernal keratoconjunctivitis in children.
AB - OBJECTIVE: To compare the efficacy of 0.1% tacrolimus (FK-506) ophthalmic
ointment with 2% cyclosporine eye drops in the treatment of vernal
keratoconjunctivitis (VKC). DESIGN: Prospective double-masked randomized
comparative trial. PARTICIPANTS: Twenty-four VKC patients were enrolled into the
study. Their mean age was 9.61 +/- 2.55 years. Twelve patients were allocated
into the FK-506 group and the other twelve into the cyclosporine group. Their
baseline characteristics were similar between groups. METHODS: After a 2 week run
in period, patients were randomized into 2 groups in a double-masked, parallel
fashion. Group A received 0.1% FK-506 eye ointment twice daily with placebo eye
drops four times daily for 8 weeks. Group B received 2% cyclosporine eye drops
with placebo ointment for the same duration. All patients received an open
treatment with 0.1% FK-506 eye ointment for another 4 weeks. Subjective ocular
symptoms and side effects were recorded by patients once daily, during the entire
period. Objective ocular signs were evaluated and scored at each follow up visit.
MAIN OUTCOME MEASURE: Improvement of total subjective symptom scores per day
(TSSS) within group and between groups at various time points. RESULTS: For
within group comparison, there was a significant decrease in TSSS, compared to
their baselines, at weeks 4 and 8, in both treatment groups. However, no
statistical difference in TSSS was noted between groups at any time point. Total
ocular sign scores (TOSS) in the FK-506 group decreased significantly at weeks 4
and 8 compared to baseline. Although there was a decrease of TOSS in the
cyclosporine group, the difference did not reach statistical significance. Side
effect scores reduced significantly in both groups at week 4 compared to their
respective baselines (p = 0.034 in the FK506 group and p = 0.003 in the
cyclosporine group). There was no significant difference in the comparison
between groups on TOSS and side effect scores at any time point of the study.
During the open FK-506 period, patients in cyclosporine group showed further
reduction of both TSSS and TOSS. However, these changes were not statistically
significant (p > 0.05). CONCLUSION: 0.1% FK-506 eye ointment and 2% cyclosporine
were both effective in treatment of VKC. 0.1% FK-506 could become another viable
therapeutic option for VKC.
PMID- 23156847
TI - The effect of acute exhaustive and moderate intensity exercises on nasal cytokine
secretion and clinical symptoms in allergic rhinitis patients.
AB - BACKGROUND: Allergic rhinitis is an inflammation of the nasal mucosa in response
to allergens. There is evidence that exercise can significantly improve personal
health and has positive effects on immune function. However, the effects of acute
exercise on the inflammatory response and clinical symptoms in patients with
allergic rhinitis are still unclear. PURPOSE: The aim of the present study was to
determine the effects of acute exhaustive and moderate exercises on cytokine
levels and clinical symptoms in patients with allergic rhinitis. METHODS:
Thirteen allergic rhinitis patients (AR) and 14 healthy subjects (C) were
required to complete two running exercise protocols, which included an exhaustive
exercise bout using the Bruce protocol performed to exhaustion and moderate
exercise performed at 65-70% HRR for 30 minutes. Physiological characteristics,
allergic rhinitis symptoms, and cytokine secretions and serum levels were
comparatively analyzed before and after each type of exercise. RESULTS: The total
immunoglobulin E levels in the AR group were significantly higher than in C group
(p < 0.05). Rhinitis symptoms scores were significantly decreased (p < 0.05)
after both exhaustive exercise (7.69 to 1.23 points) and moderate exercise (6.46
to 0.53 points) in the AR group. The ratio of interleukin-2 and interleukin-4 (IL
2/IL-4) in nasal secretions after moderate exercise was significantly higher than
those after exhaustive exercise in both the C and AR groups (p < 0.05).
CONCLUSIONS: The data demonstrate that both exhaustive and moderate-intensity
exercise resulted in a significant improvement in the symptoms of allergic
rhinitis. However, a significantly enhanced IL-2/IL-4 ratio was found following
acute moderate exercise intensity. We propose that moderate-intensity exercise is
more effective than exhaustive exercise in enhancing immune function for allergic
rhinitis patients.
PMID- 23156848
TI - Inpatient asthma mortality in a tertiary referral hospital from 2000 to 2010.
AB - OBJECTIVE: Asthma is a common respiratory disease, the prevalence of which varies
according to multiple demographic and economic factors. The availability of
therapy and implimentation of treatment guidelines has made the asthma mortality
rate stable or gradually in decline. This study was conducted to evaluate the
mortality trend of asthmatic patients who died during hospitalization in a
tertiary care center. METHODS: A retrospective study of hospitalized asthmatic
patients was conducted by reviewing medical records selected on the basis of
primary or secondary diagnosis of asthma, between January 2000 and December 2010.
The record review focused on the patients admitted to the institution who died
with the principal diagnosis of asthma or having asthma as a co-morbidity.
RESULTS: Between January 2000 and December 2010, a total of 540,365 patients were
hospitalized. Of these, 553 patients were admitted with their primary or the co
principal diagnosis of asthma. In the asthma group that were admitted, 3 male and
9 female patients died during this period, or 2.17% of asthma admissions. Eight
patients died in the first five years of the study, compared to 4 in the second
half. CONCLUSION: The mortality rate of asthma in hospitalized patients has been
declining in the last ten years. This finding has shown the importance of long
term medication used to provide good disease control and the use of asthma
treatment guidelines which may lead to the overall decreases in mortality rate.
PMID- 23156849
TI - Potent inflammatory cytokine response following lung volume recruitment maneuvers
with HFOV in pediatric acute respiratory distress syndrome.
AB - OBJECTIVE: Lung volume recruitment maneuver (LVRM) may improve gas exchange but
inflating the lungs to nearly vital capacity may cause further lung injuries. Our
aim was to determine the potent inflammatory cytokine response following lung
volume recruitment (LVRM) with high frequency oscillator ventilation (HFOV) in
pediatric acute respiratory distress syndrome (ARDS). METHODS: We prospectively
recruited pediatric patients (age >1 month - <15 year old) with a diagnosis of
ARDS within 72 hrs of PICU admission. They underwent the LVRM protocol combined
with HFOV. Any enrolled subject who had a 20% improvement in PaO2/FiO2 (PF ratio)
1 hr after the LVRM we classified as a responder. Baseline clinical data were
recorded. Blood was also drawn at baseline, 1 & 24 hrs after LVRM and kept for
further sICAM-1, IL-6 & IL-8 analysis. RESULTS: Eighteen children with ARDS were
enrolled. Their mean age was at 6.8 +/- 6.1 years (mean +/- SD). The initial
oxygen index (iOI) was at 26.8 +/- 17.8 (11.5-84.9). There was no significant
differences in sICAM-1, IL-6 and IL-8 levels at baseline; (34 +/- 17.5, 121.7 +/-
115.15, 601.5 +/- 675 pg/ml); 1 hr (39.6 +/- 28.7, 99.8 +/- 75.5, 617.4 +/- 692.5
pg/ml) and at 24 hrs (44.23 +/- 34.4, 109.4 +/- 63.9, 737.6 +/- 922.3 pg/ml)
following LVRMs, respectively. However, there was significant difference in the
elevation of sICAM-1 levels (%change) from baseline in responders (-1.8 +/-
12.2%) vs. non-responders (47.65 +/- 43.5%) at 1 hr. Additionally, sICAM-1 levels
were also significantly higher at baseline, 1 hr and 24 hrs in non-survivors as
compared with survivors. CONCLUSION: There was no significant elevation of potent
inflammatory cytokines that may indicate further lung injuries in the majority of
our patients. However, there was significant elevation of sICAM-1 levels in non
responders and in those who did not survive that may indicate more lung injuries
in these individuals.
PMID- 23156851
TI - The effect of desloratadine on patch test reactions in Chinese patients.
AB - BACKGROUND: Few data on the effect of antihistamines on patch test results in
Chinese patients are currently available. OBJECTIVES: To evaluate the effect of
desloratadine on patch test reactions. METHODS: Patients known to have at least
one strongly positive (+ +) test with an allergen were re-patch tested after 14
to 70 days (average time interval 26.3 days) of administering oral desloratadine
5 mg twice a day for 5 days before and during the test. Patch testing was
performed with the previously recognized allergen according to the guidelines of
the ICDRG. The -to + + + system was converted into numeric values (0, 1, 2, 3, 4)
for statistic evaluation. RESULTS: Of the 58 chambers (47 patients), which were
all strongly positive (+ +) during the 1st patch test, the situation was
unchanged in 51 chambers; 4 + reactions and 2 + + + reactions were observed; and
1 chamber was negative. There was no statistically significant difference when
comparing the scores of the 1st assessment with those of the 2nd (p = 0.206). If
the patch test reaction of the patient who dropped out of the trial had changed
from strongly positive (+ +) to negative, there would still have been no
statistically significant difference between the score of the 1st assessment with
those of the 2nd ( p = 0.107). CONCLUSIONS: The reaction of a patch test is not
hampered by doubling dose of desloratadine. The anti-inflammatory effects of
desloratadine on patch test reaction may be limited.
PMID- 23156850
TI - Caesarean section and asthma in Malaysian children: a case-control study.
AB - BACKGROUND: Birth cohort studies in some countries have shown a link between
caesarean section and asthma. AIM: To determine if there is an association
between asthma and delivery via caesarean section in Malaysian children. METHOD:
This is a case-control study involving 156 children aged 3-15 years old, in a
tertiary hospital in Kuala Lumpur, Malaysia. Seventy-eight children with a
confirmed diagnosis of asthma and seventy-eight age-matched controls (no history
of asthma or wheezing) were enrolled. Demographic data including mode of delivery
and family history of allergic disorders was obtained. Total serum immunoglobulin
E (IgE) was measured and skin prick tests (SPT) to 6 common aeroallergens were
performed. RESULTS: The median age of the patients was 8 years old. One hundred
and three (66%) children were delivered via normal vaginal delivery, 8 (5.1%) via
assisted vaginal delivery and 45 children (28.9%) via caesarean section. Delivery
via caesarean section was not significantly associated with asthma (OR = 1.21
[95% CI 0.60-2.41], p = 0.596). Children delivered via caesarean section did not
have higher IgE levels nor were they more sensitized to aeroallergens. Multiple
logistic regression showed that asthma was significantly associated with a
positive family history of atopy (OR = 13.8 [95% CI 5.96, 32.1], p < 0.001).
Introduction of semi-solid food after 6 months old had a protective effect
against asthma (OR = 0.97 [95% CI 0.94, 0.99], p = 0.034). CONCLUSION: Childhood
asthma in Malaysian children was not associated with delivery by caesarean
section.
PMID- 23156852
TI - A two-step non-flowcytometry-based naive B cell isolation method and its
application in Staphylococcal enterotoxin B (SEB) presentation.
AB - BACKGROUND: To study the role of human naive B cells in antigen presentation and
stimulation to naive CD4+ T cell, a suitable method to reproducibly isolate
sufficient naive B cells is required. METHODS: To improve the purity of isolated
naive B cells obtained from a conventional one-step magnetic bead method, we
added a rosetting step to enrich total B cell isolates from human whole blood
samples prior to negative cell sorting by magnetic beads. The acquired naive B
cells were analyzed for phenotypes and for their role in Staphylococcal
enterotoxin B (SEB) presentation to naive CD4+ T cells. RESULTS: The mean (SD)
naive B cell (CD19+/CD27-) purity obtained from this two-step method compared
with the one-step method was 97% (1.0) versus 90% (1.2), respectively. This two
step method can be used with a sample of whole blood as small as 10 ml. The
isolated naive B cells were phenotypically at a resting state and were able to
prime naive CD4+ T cell activation by Staphylococcal enterotoxin B (SEB)
presentation. CONCLUSIONS: This two-step non-flow cytometry-based approach
improved the purity of isolated naive B cells compared with conventional one-step
magnetic bead method. It also worked well with a small blood volume. In addition,
this study showed that the isolated naive B cells can present a super-antigen
"SEB" to activate naive CD4 cells. These methods may thus be useful for further
in vitro characterization of human naive B cells and their roles as antigen
presenting cells in various diseases.
PMID- 23156853
TI - Multiplex PCR for identifying common dust mites species (Dermatophagoides
pteronyssinus, Dermatophagoides farinae and Blomia tropicalis).
AB - INTRODUCTION: Dust mites are known to be an important source of inhalant
allergens causing allergic rhinitis and asthma worldwide. The sizes of dust mite
populations in patients' houses are useful to monitor the risk of allergen
exposure. However, mite identification using the conventional microscopic
technique requires specific expertise and is time consuming; therefore a
molecular technique has been developed in order to solve these drawbacks.
OBJECTIVE: To develop a multiplex PCR assay for identifying the three common dust
mite species in Thailand, namely Dermatophagoides pteronyssinus (Dp), D. farinae
(Df) and Blomia tropicalis (Bt), and to evaluate the efficacy of the technique.
METHODS: Pairs of primers were designed and tested in either singleplex PCR or
multiplex PCR. The multiplex PCR technique was also optimized in order to obtain
specific products. The reaction mixture contained 5 pmole of individual primers,
10 mM dNTP, 5 units Taq DNA polymerase and genomic DNA (gDNA). The reaction was
run for 25 cycles at 94 degrees C for 20 seconds, 58 degrees C for 20 seconds and
72 degrees C for 30 seconds. The PCR products were analyzed by 1.5% agarose gel
electrophoresis with GelRed fluorescence dye. The optimized multiplex technique
was also tested with 30 house dust samples and dust samples spiked with DNA from
other insect and mite species. RESULTS: Three PCR products were obtained with the
relevant gDNA templates as expected; 143 bp for DF, 221 bp for DP and 318 bp for
BT, respectively. The detection limit of the tests was found to be as low 1 ng of
gDNA, whereas mixed gDNA species confirmed the 100% specificity of this assay.
The total duration from the preparation of the PCR reaction mixture until the
analysis by agarose gel electrophoresis was approximately 2 hours. No amplified
product was obtained from mites and insects of other species. CONCLUSION: The
multiplex PCR was successfully developed for identifying 3 common dust mite
species. This technique can be helpful, not only for non-acarologist personnel
for dust mite identification, but also for patients who are allergic to dust
mites.
PMID- 23156854
TI - Comparison of allergenic components and biopotency in whole body extracts of wild
and laboratory reared American cockroaches, Periplaneta americana.
AB - BACKGROUND AND OBJECTIVE: Most allergen extracts/vaccines used today in clinical
practice are derived from natural allergen sources. Therefore, their allergic
components may vary as these are prone to natural variation. This study aims to
compare the allergenic components and biological potency of crude extracts from
wild and laboratory reared American cockroaches. METHODS: Crude extracts of male
and female of wild and laboratory reared American CR, were prepared by the same
method. Their allergenic components were evaluated by in vitro assays such as
protein contents, protein profiles, quantification of major allergens (Per a 1
and Per a 9) and IgE inhibition ELISA assay. RESULTS AND DISCUSSION: There was no
statistically significant difference between the protein contents and the
concentrations of Per a 1 in the crude extracts from both groups. However, the
Per a 9 levels in extracts of wild CR were significantly higher than those from
the extracts of laboratory reared CR. The protein patterns of the extracts of
laboratory reared CR exhibited more consistency in the number of bands with
higher intensity than those of wild CR. Pooled extracts of laboratory reared CR
could inhibit IgE binding to that of wild CR up to 78%. The endotoxin content of
extracts of laboratory reared CR were ten times less than those of the the wild
CR. We have successfully determined the allergenic potency of the extracts of
laboratory reared CR versus those of the wild CRs by in vitro assays. Further
studies should be performed to determine the biological potency of CR extracts by
in vivo assays for clinical application. CONCLUSION: Our finding indicates that
the laboratory reared CR would be the better source of material in vaccine
production than the wild CR.
PMID- 23156855
TI - Medullary ischemia due to vertebral arteritis associated with Behcet syndrome: a
case report.
AB - Here we report an extremely rare case of Behcet syndrome (BS) that showed acute
onset of Wallenberg syndrome and was treated successfully by corticosteroids. A
51-year-old woman with BS had a sudden onset of Wallenberg syndrome. Three days
after the onset, she was transferred to our institute. In the magnetic resonance
imaging (MRI) study on admission, T2-weighted and fluid-attenuated inversion
recovery images showed a high intensity area in the left paramedian region of the
medulla oblongata. Contrast-enhanced T1-weighted images showed enhancement in the
vessel wall of the left vertebral artery. We diagnosed her as having Wallenberg
syndrome due to the acute vertebral arteritis associated with BS. After
initiation of high-dose steroid therapy, her symptoms gradually improved. Two
months after admission, she was discharged from our institute with mild
hemihypesthesia. We hypothesized that vertebral arteritis due to BS had caused
hypoperfusion of the medullary perforators causing Wallenberg syndrome in our
patient.
PMID- 23156856
TI - Sodium nitroprusside and toxic epidermal necrolysis.
AB - Sodium nitroprusside (SNP) is one of the most widely used parenteral
antihypertensive agents in severe hypertension management. Toxic epidermal
necrolysis (TEN) is a rare, mostly drug-induced, severe muco-cutoneous reaction
with various complications and high mortality. A fifteen years old girl who is on
hemodialysis for chronic renal insufficiency and was hospitalized for emergency
management of hypertension, developed a diffuse maculopapular rash within minutes
after SNP infusion. In 72 hours, approximately 40% of the body surface was
involved with skin detachment indicating epidermal necrolysis and a skin biopsy
confirmed the diagnosis of TEN. To the best of our knowledge there is no report
of an association of SNP and TEN in the English literature and the clinical data
exemplifying consequent IgE and non-IgE mediated hypersensitivity reactions are
scanty. With this report we wanted to present a rare complication of SNP infusion
indicating another rare occurrence of sequential IgE and non-IgE mediated
hypersensitivity reactions.
PMID- 23156857
TI - [Joint pain and swelling. What kind of tumor in the toe? Gout tophi].
PMID- 23156858
TI - [Summer in the intensive care unit. Why did the patient get blisters on the
abdomen? Miliaria cristallina].
PMID- 23156859
TI - [2012 Nobel Prize in Medicine. Cellular rejuvenation for diversity].
PMID- 23156860
TI - [New STIKO recommendations. Booster vaccinations may be used generously].
PMID- 23156861
TI - [Emergency decision at the death bed. When should the defibrillator be shut
off?].
PMID- 23156862
TI - [German guidelines are overdue. When ICD's impede dying (interview by Dr. med.
Jochen Aumiller)].
PMID- 23156863
TI - [New diabetes guidelines in the EU and USA. Rigid HbA1c specifications are
history!].
PMID- 23156864
TI - [Heart and lung functioning normally. Where does the dyspnea come from?].
PMID- 23156865
TI - [In CNS symptoms remember: sepsis is an encephalopathy!].
PMID- 23156866
TI - [Investigative strategies in increased liver values. Necrosis or cholestasis?].
PMID- 23156867
TI - [Effectiveness of phytochemicals. Broccoli in intestinal infections? (interview
by Dr. Beate Schumacher)].
PMID- 23156868
TI - [District level as kicker, but at the top in action].
PMID- 23156869
TI - [Rehabilitation medications].
PMID- 23156870
TI - [Abdomen in social network].
PMID- 23156871
TI - [My student has a psychosis. How should I behave?].
PMID- 23156872
TI - [Tinnitus and hearing loss. Can a cochlear implant help in this case?].
PMID- 23156873
TI - [Renal denervation. How high is the rate of complications?].
PMID- 23156874
TI - [No tumor in colonoscopy 2 years ago. Now the patient has a positive hemoccult
test - how to proceed?].
PMID- 23156875
TI - [Angiology is more than peripheral vascular disease].
PMID- 23156876
TI - [Congenital vascular malformations].
PMID- 23156877
TI - [Scarlet fever].
PMID- 23156878
TI - [Problems in intravenous access in outpatient emergency? There are
alternatives!].
PMID- 23156879
TI - [Vaccinations for travelers].
PMID- 23156880
TI - [Hypertension: most important risk factor of a stroke].
PMID- 23156881
TI - [Migration and pain].
PMID- 23156882
TI - [Chronic ischemic heart diseases. Effectively alleviating ischemia symptoms].
PMID- 23156883
TI - [Relative improvement of the quality of life (interview by Philip Grazel)].
PMID- 23156884
TI - [New fixed combination for asthma patients. Fluticasone plus formoterol - proven
drugs for the first time in fixed combination].
PMID- 23156885
TI - Damas hospital compliance to American College of Cardiology reperfusion therapy
during acute ST-elevation myocardial infarction.
AB - Despite improvements in care, up to one-third of patients presenting with ST
elevation myocardial infarction (STEMI) within 12 hours of symptom onset receive
no reperfusion therapy. Despite effective pre- and in-hospital reperfusion
strategies becoming standard over the past two decades, time-to-admission and
time-to-treatment remains prolonged. Prompt reperfusion treatment is essential to
decrease mortality. The ACC/AHA guidelines recommend that the interval between
arrival at the hospital and intracoronary balloon inflation during percutaneous
coronary intervention should be within ninety minutes of patient arrival to the
ED or less and within 30 minutes for fibrinolytic therapy. However, few hospitals
meet this objective. We did a retrospective analysis of patients with STEMI from
January 2008 to December 2010. From an initial list of 57 patients, only 45
patients presented with confirmed STEMI. Of these, 35 had indication for
reperfusion therapy. 97% received fibrinolytic therapy versus 3% who underwent
percutaneous coronary intervention (PCI). The reperfusion time goal was achieved
in 45% of cases treated with fibrinolytic therapy. Most of the patients
presenting with STEMI undergo reperfusion therapy with fibrinolytic therapy. PCI
was not performed as initial reperfusion therapy, even at regular duty hours.
Reperfusion therapy was performed beyond the expected time goal in more that half
of the cases. The most significant delay was related to nursing staff
performance.
PMID- 23156886
TI - Evaluation of a vancomycin dosing regimen for patients on high flux hemodialysis:
an observational study.
AB - Vancomycin is the mainstay antibiotic used in hemodialysis group due to high
prevalence of methicillin resistant Staphylococcus Aureus. For years regimens of
vancomycin in high flux hemodialysis (HFHD) patients were designed to achieve a
pre-dialysis vancomycin concentration between 5-20 ug/mL. Recent guidelines
increased the recommended pre-dialysis level to 15-20 ug/ml for health care
associated infections, bacteremia and osteomyelitis. The purpose of this study
was to determine if the loading dose (LD) before HFHD and the maintenance dose
(MD) of vancomycin achieved a pre-dialysis concentration between 15-20 ug/ml on
HFHD in-patients with a suspected infection. The second purpose was to predict an
adequate vancomycin dosage to achieve the new recommended levels. MATERIAL AND
METHODS: An observational prospective study on hospitalized adult patients on
HFHD with evidence of infection treated with 1 gm LD of vancomycin and 500 mg MD.
Plasma levels of vancomycin were measured before each HFHD for three consecutive
times. Age, gender, weight at admission, blood flow rate, dialyzer flow rate,
type of filter and HFHD length were evaluated. RESULTS: Twenty-one patients met
the inclusion criteria. All of them were treated with 1 gm LD of vancomycin and
500 mg MD protocol. The mean pre-dialysis concentration #1 was 10.8 ug/mL. The
mean pre-dialysis concentration #2 was 13 ug/mL, and the mean pre-dialysis
concentration #3 was 12 ug/mL. Only 36% of HFHD sessions achieved an adequate
vancomycin level. A liner regression analysis predicted that a loading dose of 23
mg/kg LD and 8 mg/kg MD achieved the recommended pre-dialysis vancomycin
concentration. CONCLUSIONS: Current dose regimen of 1 gm LD and 500 mg MD of
Vancomycin are not adequate to achieve recommended pre-dialysis level of 15-20
ug/mL for health care associated infections, bacteremia and osteomyelitis in most
patients on HFHD. Based on our statistical analysis, we recommended that 23 mg/kg
of LD and 8 mg/kg of MD would achieve an adequate vancomycin level.
PMID- 23156887
TI - Severe hypertriglyceridemia in Puerto Rico blood donors: a population study 2009
2011.
AB - Puerto Rico blood donor issues has been identified in cases of severe
hypertriglyceridemia presenting as turbid. Blood donations resulting in milky
serum must be discarded. They are discarded because we cannot properly test the
donation. This is the first report where we correlate turbidity and
cardiovascular risk factors in the Puerto Rico population as well as blood types
O and A, Rh (+) with dyslipidemia. Blood donors should be screened in more
details regarding cardiovascular and metabolic risks to avoid problems with
recruitment and retention strategies.
PMID- 23156888
TI - Outcomes of glycemic control in Hispanic geriatric diabetic patients admitted to
a general ward community hospital in Puerto Rico.
AB - BACKGROUND: Diabetes mellitus is one of the most prevalent medical conditions
among the Hispanic population. Although studies with patients in intensive care
units have shown poor outcomes among those with uncontrolled glucose, more recent
data have shown increased mortality associated with a tighter inpatient glucose
control. In view of the lack of information regarding geriatric Hispanic patients
with diabetes this study evaluated the effect of glucose control in the outcomes
of this population in a community hospital in Puerto Rico. METHODS: Through
analysis of data from a previous study we evaluated 502 admissions of Hispanic
geriatric patients with diabetes as comorbidity, for glucose control, management
of diabetes and outcome. Data was stratified by age groups (65-74 years, 75-84
years and > or = 85 years) and outcomes were compared between the groups using
chi-square and odds ratio. RESULTS: The most common admission diagnosis was
pneumonia. Hypoglycemia was the most common complication and was associated with
tighter glucose control in the age group of 75-84 years. An increased risk of
having an acute coronary syndrome/acute myocardial infarction among uncontrolled
patients was observed in the 75-84 year old group. Finally, although we found a
high prevalence of uncontrolled blood glucose, only 54% of the patients received
interventions for their glucose control. CONCLUSIONS: Poor glucose control seems
to be associated with a tendency for decreased risk of hypoglycemia and higher
risk of acute coronary syndrome/acute myocardial infarction as complications
among geriatric patients with diabetes admitted to a general ward.
PMID- 23156889
TI - [Orbital tumors: experience with 35 cases].
AB - Tumors of the orbit are pathology of considerable complexity in management due to
the diverse anatomic and muscular, vascular, cartilagenous and neural components
present. We review a series of 35 cases managed at the National Institute of
Cancer in Bogota, Colombia. We determine variables such as age, sex, symptoms,
histology, location and surgical procedure of these tumors. This review suggest
that this complex pathology should be managed by a multidisciplinary team with
extensive neurosurgical experience to obtain satisfactory results.
PMID- 23156890
TI - Pulmonary metastasectomy for children with malignant tumors.
AB - In children with primary solid malignant tumors the most frequent site of
metastasis is usally the lung. Pulmonary metastasectomy is part of the standard
of care in adult malignancies but its role in pediatric patients has been poor
characterized. This review article discusses the benefits, outcomes according
tumor histology, selection criteria, adjuvant therapies and surgical techniques
employed in the resection of pulmonary metastases in children with malignant
tumors.
PMID- 23156891
TI - No asthma, no parasites is a rare type of leukemia: chronic myeloid neoplasm with
eosinophilia and abnormality of platelet-derived growth factor receptor alpha.
AB - Chronic myeloid neoplasm with eosinophilia and abnormality of platelet-derived
growth factor receptor alpha (PDGFRA), referred as chronic eosinophilic leukemia,
is an extremely rare neoplasm where long-term prognosis is uncertain though a
high grade of responsiveness to Imatinib has been reported. The mortality and
morbidity associated with chronic eosinophilic leukemia is associated with the
degree of tissue involvement, damage, or both at diagnosis. We discuss a case of
a young male patient with past medical history of hypoglycemia that presented to
the emergency room with a complaints of a sharp abdominal pain localized in the
upper quadrants. Laboratories were remarkable for elevated white blood cells with
eosinophils predominance, anemia and thrombocytopenia. Bone marrow biopsy
dislocated a FIP1L1-PDGFRA fusion gene chronic eosinophilic leukemia. Physicians
need to have a high index of suspicion of this rare entity since not all
eosinophilias can be interpreted as asthma or parasitis infections.
PMID- 23156892
TI - Intrathoracic kidney in a child: case report and review of literature.
AB - Intrathoracic ectopic kidney is a rare congenital abnormality with a prevalence
estimated as less than one in 10000 and with only thirteen cases reported in the
pediatric age group over the past twenty-five years. Herein, we report the
uncommon case of a 20 month-old-male exhibiting a left ectopic intrathoracic
kidney diagnosed as an incidental finding in image studies. Uncomplicated
incidentals diagnosis has demonstrated normal function and development of those
kidneys in long-term follow-up with no late bowel herniation.
PMID- 23156894
TI - Synovial sarcoma of the hypopharynx in pregnancy.
AB - Synovial sarcomas of the hypopharynx are a rare form of soft tissue sarcomas. In
the head and neck, they are most commonly found on the pharyngeal wall in areas
that do not have synovial cells. We review a case of a 23 year-old pregnant
female who presented to our hospital with acute airway obstruction due to a large
hypopharynx lesion. She underwent emergency tracheotomy and tumor debulking.
Pathology revealed synovial sarcoma. After the procedure the patient went into
labor delivering a 29 weeks premature child. Six weeks after being discharged
from the hospital the patient had a partial pharyngectomy performed to excise the
remnant base of the tumor. She has had no recurrence at the 30-month post
operative period.
PMID- 23156893
TI - Secondary biliary cirrhosis due to a rare choledochal cyst type II complicated
with portal hypertension and pancytopenia in a young female patient.
AB - Choledochal cyst type II, is an extremely rare cause of portal hypertension,
severe pancytopenia in an adult patient, and a complication of long-standing
disease. We present an uncommon cause of portal hypertension in a young female
patient secondary to an obstructive choledochal cyst type II provoking massive
splenomegaly and severe pancytopenia. A high level of clinical suspicion is
important due to its high mortality rate if it remains undiagnosed. To our
knowledge there are few publications describing this rare type of choledochal
cyst in a Hispanic adult.
PMID- 23156895
TI - [Rapidly progressive compromise of cranial pairs as neurosyphilis manifestation].
AB - Syphilis remains a common disease throughout the world, being neurosyphilis a
relatively common manifestation. A case of a 34 years old male with HIV and
neurosyphilis is presented, characterized by a clinical course evidenced by
progressive palsy of cranial nerves. This case is unusual and a rare presentation
of progressive cranial involvement with swallowing deficit, have found no similar
data in the literature.
PMID- 23156896
TI - Immuno compromised patients: what a challenge!
AB - Mucormycosis is an uncommon but fatal fungal infection of airborne transmission.
Its is usually seen in immunocompromised patients including diabetics,
malignancies, transplant patients and renal insufficiency. We review the case of
an immunocompromised patient unresponsive to broad-spectrum antibiotics and
conventional antifungal therapy with lung mucormycosis.
PMID- 23156897
TI - Relational learning in glaucous-winged gulls (Larus glaucescens).
AB - An experimental approach was created for the comparative investigation of the
cognitive abilities of the glaucous-winged gull (Larus glaucescens) in their
natural habitat. The territoriality of gulls during the breeding period and the
fact that the gulls inhabiting the territory of the Komandorsky Reserve are
practically not in fear of humans allowed us to work with individually recognized
birds directly at their nest sites inside the colony. The possibility of using
this approach to investigate their cognitive abilities was demonstrated on 24
gulls, in particular, to investigate their abilities for relative size
generalization. The first experiment illustrated that the gulls are able to learn
to discriminate two pairs of stimuli according to the feature: 'larger' or
'smaller'. They were then given a test to transfer the discriminative rule in
which novel combinations of the same stimuli were used. The gulls successfully
coped with only a few of these tests. In the next experiment the birds were
taught to discriminate four pairs of similar stimuli. The majority of the birds
coped with the tests to transfer the discriminative rule both to the novel
combinations of familiar stimuli, and also to the novel stimuli of the familiar
category (items of different colour and shape). However, none of the birds
transferred the discriminative rule to stimuli of a novel category (sets
differing by number of components). Thus, in their ability to generalize at a
preconceptual level gulls are more comparable with pigeons, whereas large-brained
birds (crows and parrots), are capable of concept formation.
PMID- 23156898
TI - Working memory capacity and mental rotation: evidence for a domain-general view.
AB - Despite the existence of numerous studies that examined the relationship between
working memory capacity and performance in complex cognitive tasks, it remains
unclear whether this capacity is domain specific or domain general. In addition,
the available empirical evidence is somewhat contradictory. In this work we have
studied the role of verbal working memory capacity in a non-verbal task--mental
image rotation. If this capacity were domain specific it would be expected that
high and low verbal span participants would obtain similar results in the mental
rotation task. We have found that this is not the case as the high span
participants performed better in terms of both speed and accuracy. Moreover,
these differences depended on the processing component of the mental rotation
task: the higher the processing requirements the higher the differences as a
function of the working memory capacity. Therefore, the evidence presented here
supports the domain general hypothesis.
PMID- 23156899
TI - Masked and unmasked priming effects as a function of semantic relatedness and
associative strength.
AB - The study presented in this paper aimed to investigate the pattern of semantic
priming effects, under masked and unmasked conditions, in the lexical decision
task, manipulating type of semantic relation and associative strength. Three
different kinds of word relations were examined in two experiments: only
semantically related words [e.g., codo (elbow)-rodilla (knee)] and
semantic/associative related words with strong [e.g., mesa (table)-silla (chair)
and weak association strength [e.g., sapo (toad)-rana (frog)]. In Experiment 1 a
masked priming procedure was used with a prime duration of 56 ms, and in
Experiment 2, the prime was presented unmasked for 150 ms. The results showed
that there were masked priming effects with strong associates, but no evidence of
these effects was found with weak associates or only-semantic related word pairs.
When the prime was presented unmasked, the three types of relations produced
significant priming effects and they were not influenced by association strength.
PMID- 23156900
TI - The role of perceptual information in familiarity-based scene recognition.
AB - A method to analyze the role of familiarity in recognizing pictures of everyday
scenes is introduced. The idea is to manipulate two within-subjects conditions:
an experimental condition where the scenes repeat perceptual information (e.g.
buildings and/or vehicles) and a control condition. The results show the two
conditions did not differ in terms of hit rates, but in the experimental
condition there were significantly fewer false alarms, yielding better results,
which supports the findings of past research studies that have used verbal
materials. This perceptual facilitation was maintained throughout a week-long
retention interval. Finally, a detailed analysis of this facilitation shows it
was due to a significant reduction in false alarms on know judgments, emphasizing
familiarity's role in explaining this effect.
PMID- 23156901
TI - Aversive priming: cognitive processing of threatening stimuli is facilitated by
aversive primes.
AB - It would be reasonable to expect that our previous experience regarding a
stimulus that predicts harm would make the subsequent identification of that
stimulus easier when harm happens again. Forty-eight volunteers were submitted to
both phases of this sequence of events: learning of the predictive relationship
and later priming. A face with neutral expression (CS+) was paired with a
moderately aversive electric shock and another (CS-) with a neutral tone.
Subsequently, these two faces, as well as other known and new faces, were
presented for familiarity judgments. Both the CS+ and the CS- faces were preceded
by an aversive stimulus (aversive prime) in one occasion and by a neutral
stimulus (neutral prime) in another. The familiarity judgment regarding the CS+
was faster after the aversive prime than after the neutral prime, but there was
no difference regarding the CS-. The differential effect of the aversive prime
over the CS+ and the CS- showed a significant but small correlation with the
differential skin conductance response to CS+ and CS- (signal learning), and with
the differential evaluation of those stimuli in terms of like-dislike (evaluative
learning). The scope of these results, as well as the usefulness of this
methodological model, is discussed.
PMID- 23156902
TI - Impulsivity, intelligence, and discriminating reinforcement contingencies in a
fixed-ratio 3 schedule.
AB - Research conducted in academic contexts suggests a moderating effect of impulsive
behavior on the relationship between aptitude and achievement. According to these
studies, intelligence scores being equal, higher levels of impulsivity have an
adverse effect on achievement (Helmers, Young, & Pihl, 1995; Vigil-Colet &
Morales-Vives, 2005; Zeidner, 1995). The present study aims to contrast the
aforementioned moderator effect in the context of a discriminant learning task,
carried out under a fixed-ratio 3 reinforcement schedule. To that end, an
impulsive behavioral pattern was identified in a sample of 1,600 participants'
task execution based on response rate and latency. Said pattern was consistent
and stable across several trials and can be ascribed to subjects' interactive
style (Hernandez, 2000). The observed interaction effect supports the hypothesis
that impulsivity has a moderating effect on the aptitude-achievement
relationship, highlighting how it impacts achievement differentially depending on
the subject's level of aptitude.
PMID- 23156903
TI - Clinical efficacy of a new automated hemoencephalographic neurofeedback protocol.
AB - Among the ongoing attempts to enhance cognitive performance, an emergent and yet
underrepresented venue is brought by hemoencefalographic neurofeedback (HEG).
This paper presents three related advances in HEG neurofeedback for cognitive
enhancement: a) a new HEG protocol for cognitive enhancement, as well as b) the
results of independent measures of biological efficacy (EEG brain maps) extracted
in three phases, during a one year follow up case study; c) the results of the
first controlled clinical trial of HEG, designed to assess the efficacy of the
technique for cognitive enhancement of an adult and neurologically intact
population. The new protocol was developed in the environment of a software that
organizes digital signal algorithms in a flowchart format. Brain maps were
produced through 10 brain recordings. The clinical trial used a working memory
test as its independent measure of achievement. The main conclusion of this study
is that the technique appears to be clinically promising. Approaches to cognitive
performance from a metabolic viewpoint should be explored further. However, it is
particularly important to note that, to our knowledge, this is the world's first
controlled clinical study on the matter and it is still early for an ultimate
evaluation of the technique.
PMID- 23156904
TI - Comparison of neuropsychological performance between students from public and
private Brazilian schools.
AB - Neuropsychological assessment reveals that certain cognitive changes that take
place during the neural development process may be associated with
biopsychosocial issues. A substantial body of research has focused on cognitive
development in children and adults, but few such studies have been carried out on
adolescents. Therefore, research into the processing of neuropsychological
functions in adolescents, taking into account the role of major socio-cultural
factors such as school type (public vs. private), is highly relevant. The present
study sought to assess whether differences in neuropsychological development
exist between adolescent students of public (government-funded) and private
schools. A total of 373 grade-matched students between the ages of 12 and 18, 190
from public schools and 183 from private schools, took part in the study. All
subjects had no self-reported neurologic or psychiatric conditions and sensory
disorders. The NEUPSILIN Brazilian Brief Neuropsychological Assessment Battery
was administered to this sample. Comparison of mean scores (one-way ANCOVA with
socioeconomic score and age as covariates) showed that adolescents attending
private schools generally outperformed their public-school peers in tasks
involving sustained attention, memory (working and visual), dictated writing, and
constructional and reflective abilities. We conclude that school type should be
taken into account during standardization of neuropsychological assessment
instruments for adolescent and, probably, child populations.
PMID- 23156905
TI - Symbolic and non-symbolic number magnitude processing in children with
developmental dyscalculia.
AB - The aim of this study was to evaluate if children with Developmental Dyscalculia
(DD) exhibit a general deficit in magnitude representations or a specific deficit
in the connection of symbolic representations with the corresponding analogous
magnitudes. DD was diagnosed using a timed arithmetic task. The experimental
magnitude comparison tasks were presented in non-symbolic and symbolic formats.
DD and typically developing (TD) children showed similar numerical distance and
size congruity effects. However, DD children performed significantly slower in
the symbolic task. These results are consistent with the access deficit
hypothesis, according to which DD children's deficits are caused by difficulties
accessing magnitude information from numerical symbols rather than in processing
numerosities per se.
PMID- 23156906
TI - Executive attention and personality variables in patients with frontal lobe
damage.
AB - Executive Control is required to deal with novel situations or when an action
plan is needed. This study aimed to highlight the executive attention deficits of
patients with frontal lobe damage. To do so, the ANT-I task (Attention Network
Test-Interactions) was administered for the first time to a group of 9 patients
with frontal damage caused by traumatic brain injury (TBI) and a matched control
group. This task made it possible to measure the three attentional networks
proposed by Posner and Dehaene (1994) and their interactions. Results on the
alerting and orienting networks did not show any significant differences between
the groups. However, a significant effect of group on the executive control
network was observed. In addition, participants' personality was assessed with a
clinical inventory (the Millon Personality Inventory) that showed a significant
positive correlation between borderline personality disorder and the conflict
index. These results suggest that frontal lobe damage causes an exclusive
impairment in the conflict resolution network that is related to personality
traits characterized by a lack of behavioral control. More research will be
necessary to study this causal relationship.
PMID- 23156907
TI - Infant crying: pattern of weeping, recognition of emotion and affective reactions
in observers.
AB - This study has three objectives: a) to describe the main differences in the
crying patterns produced by the three affective states most closely related to
crying: fear, anger and pain; b) to study the adults' accuracy in the recognition
of the affective states related to the infant's crying, and c) to analyze the
emotional reaction that infant crying elicits in the observers. Results reveal
that the main differences appear in the ocular activity and in the pattern of
weeping. The infants maintain their eyes open during the crying produced by fear
and anger, but in the case of crying provoked by painful stimuli, the eyes remain
closed almost all the time. In regard to the pattern of weeping, the crying
gradually increase in the case of anger, but the weeping reaches its maximum
intensity practically from the beginning in the case of pain and fear. In spite
of these differences, it is not easy to know the cause that produces crying in
infants, especially in the case of fear or anger. Although observers can't
recognize the cause of crying, the emotional reaction is greater when the baby
cries in pain than when the baby cries because of fear or anger.
PMID- 23156908
TI - Profiles of maternal care observed in a group of Brazilian mothers: an
exploratory study.
AB - The aim of this study is to characterize profiles of maternal care in a sample of
Brazilian mothers, using a cultural-biological perspective. Participants were 315
women who had at least one child younger than six years-old. They were selected
from six Brazilian states. In each state, two groups of mothers were studied, one
from the capital and one from a small city. They were interviewed and answered
scales on allocentrism, social support, adult attachment, and practices of
childcare. Mothers' characteristics, the type of context (capital vs. small
city), and reported childcare practices were used in a Tree analysis. A
Correspondence analysis was performed using the four clusters obtained and
mothers' answers regarding their youngest child. Univariate GLM analyses were
performed to compare mothers in the four clusters in terms of their scores on the
different scales. Four maternal profiles presenting distinctive patterns of
association between mothers' characteristics and care practices displayed to the
youngest child were identified. We conclude that maternal care is a multi
determined phenomenon and that the method employed in this study can give
insights into how the combination of diverse social-biological factors can result
in a set of childcare practices.
PMID- 23156909
TI - Attachment, emotion regulation and coping in Portuguese emerging adults: a test
of a mediation hypothesis.
AB - Although the quality of parent-adolescent emotional bonds has consistently been
proposed as a major influence on young adult's psycho-emotional functioning, the
precise means by which these bonds either facilitate or impede adaptive coping
are not well-understood. In an effort to advance this inquiry, the present study
examined interrelationships among measures of parental attachment, emotion
regulation processes, and preferred coping strategies within a sample of 942
college freshmen. Structural Equation Modelling was used to test whether the link
between attachment to parents and the use of particular coping strategies is
mediated by differences in emotion regulation mechanisms. As hypothesized,
differences in attachment to parents predicted differences in the use of emotion
regulation mechanisms and coping strategies. More specifically, having a close
emotional bond, feeling supported in autonomy processes and having (moderately)
low levels of separation anxiety toward parents predict more constructive emotion
regulation mechanisms and coping strategies. Additionally emotion regulation was
found to (partly or totally) mediate the association between attachment and
coping.
PMID- 23156910
TI - Emotional and social problems in adolescents from a gender perspective.
AB - The present study aims to analyze the relationships between community
involvement, perception of family and school climate, and emotional and social
problems in adolescents (satisfaction with life, non-conformist social
reputation, and school violence). The sample was composed of 1884 (52% boys and
48% girls) adolescents aged from 11 to 17 years old (M = 13.7, SD = 1.4) from the
Valencia Community and Andalusia. A structural equation model was calculated to
analyze the data. The results indicated that adolescent community involvement was
associated with positive perceptions of family and school climate, and school
violence. Associations between the variables of the study included in the
structural model were also analyzed as a function of gender. The relationship
between school climate and social reputation was significant only for boys.
Likewise, the association between community involvement and violent behavior was
found to be significant only for boys. Finally, the results and their possible
implications are discussed.
PMID- 23156911
TI - Substance use in Portuguese and Spanish adolescents: highlights from differences,
similarities and moderating effects.
AB - Many behaviors with lasting health impact are initiated in adolescence. Substance
use is one such behavior. To analyse the factors involved in adolescent substance
use among Portuguese and Spanish boys and girls, an explanatory model was
developed using structural equations modelling. The model proposes that the
impact of social contexts (family, friends, classmates and teachers) on substance
use (tobacco, alcohol and illicit drugs) is mediated by perceptions of well-being
(psychological symptoms, well-being and school satisfaction). Data on 1589
Portuguese (mean age = 13.27, SD = .59) and 4191 Spanish adolescents (mean age =
13.21; SD = .47) who took part in the HBSC/WHO survey were analysed. The model
fits the data of each country (CFI > .90; RMSEA < .03) and the majority of the
relationships proposed in the model have been as expected for both samples. The
relations with a major effect, for both countries, were: the negative effect of
family on psychological symptoms and the positive effect of family on subjective
well-being; the negative effect of classmates on psychological symptoms; the
positive effect of teachers on school satisfaction; the effect of psychological
symptoms (negative) and school satisfaction (positive) on well-being; the
negative effect of school satisfaction on tobacco and alcohol use; and the
positive effect of tobacco on alcohol use, and alcohol use on cannabis. For each
of the dependent factors studied (tobacco, alcohol and illicit drugs), the levels
of explained variance varied between 9% (for tobacco use) and 46% (for alcohol
use). Some non-invariant paths were obtained in country comparisons, controlling
for gender. In multivariate analyses the paths from tobacco use to cannabis and
from alcohol to cannabis were significant, but much stronger for Spanish girls
than Portuguese girls.
PMID- 23156912
TI - Effect of different professions' clothing on children's height perception.
AB - Height is a biological factor that can affect how others perceive and behave
toward an individual. Height is a biological factor that can affect how others
perceive and behave toward an individual. Clothing, as a non-biological factor,
can affect these perceptions of height. In this study weClothing, as a non
biological factor, can affect these perceptions of height. In this study we
investigated the effect of different professions' clothing on children's
perceptions of height. One investigated the effect of different professions'
clothing on children's perceptions of height. One hundred and eighty primary
school students participated in this study and estimated the height of an actor
in the clothing of four different professions which differed in terms of
prestige. The results of study showed that the difference between the perceived
and actual height was larger when participants estimated the height of socially
esteemed professions. Also there was no difference between girls' and boys'
estimation of different professions' height. The implications of these findings
are discussed.
PMID- 23156913
TI - Academic goal profiles: a comparison of blind and sighted students.
AB - Based on academic goal theory, we compared the goals of visually impaired and
sighted students. Participants included 171 students affiliated with ONCE (the
National Spanish Organization for the Blind) and 163 sighted students, ranging
from 8 to 27 years of age, who responded to the Spanish adaptation (Gonzalez,
Torregrosa, & Navas, 2002) of the goals questionnaire created by Hayamizu, Ito,
and Yohiazaki (1989) and Hayamizu and Weiner (1991). Factor analysis indicated
that goals varied among these students and that new ones arose in this study;
furthermore, the model remained invariable regardless of students' status
(visually impaired versus sighted). Cluster analysis revealed three distinct
profiles in terms of academic goals, while discriminant function analysis
suggested these profiles vary as a function of students' status (visually
impaired versus sighted). It seems that visually impaired students hold more
learning-oriented academic goals.
PMID- 23156914
TI - Academic effects of the Prestige oil spill disaster.
AB - The effect of a large scale oil spill disaster on the academic achievement and
classroom behavior of children and adolescents who lived on the Galician coast
(Spain) is studied from an ecological perspective. 430 participants divided into
three age groups of 5, 10, and 15 years of age, were studied. The participants
came from three areas differently affected by the disaster. Dependent variables
were academic achievement and classroom behavior of the participants after the
Prestige disaster. Degree of exposure and other protective or risk factors were
investigated as well. Repeated measures ANOVA to assess the main effects of the
oil spill and hierarchical regression analyses to assess the contribution of the
protective/vulnerability factors were performed. The results indicate that the
effects of the disaster were relatively scarce. Some protective factors accounted
for a certain degree of variance of different schoolroom behaviors. These results
point to the intervention of protective factors in the adaptation to the
disaster.
PMID- 23156916
TI - A correlational and predictive study of creativity and personality of college
students.
AB - The goals of this study were to examine the relationship between creativity and
personality, to identify what personality variables better predict creativity,
and to determine whether significant differences exist among them in relation to
gender. The research was conducted with a sample of 87 students at the
Universidad Publica de Navarra, Spain. We administered the Creative Intelligence
Test (CREA), which provides a cognitive measure for creativity and the
Situational Personality Questionnaire (SPQ), which is composed of 15 personality
features. Positive and significant correlations between creativity and
independence, cognitive control, and tolerance personality scales were found.
Negative and significant correlations between creativity and anxious, dominant,
and aggressive personalities were also found. Moreover, four personality
variables that positively predicted creativity (efficacy, independence, cognitive
control, and integrity-honesty) and another four that negatively predicted
creativity (emotional stability, anxiety, dominance, and leadership) were
identified. The results did not show significant differences in creativity and
personality in relation to gender, except in self-concept and in social
adjustment. In conclusion, the results from this study can potentially be used to
expand the types of features that support creative personalities.
PMID- 23156915
TI - Motivational and emotional profiles in university undergraduates: a self
determination theory perspective.
AB - Previous research has focused on specific forms of self-determined motivation or
discrete class-related emotions, but few studies have simultaneously examined
both constructs. The aim of this study on 472 undergraduates was twofold: to
perform cluster analysis to identify homogeneous groups of motivation in the
sample; and to determine the profile of each cluster for emotions and academic
achievement. Cluster analysis configured four groups in terms of motivation:
controlled, autonomous, both high, and both low. Each cluster revealed a distinct
emotional profile, autonomous motivation being the most adaptable with high
scores for academic achievement and pleasant emotions and low values for
unpleasant emotions. The results are discussed in the light of their implications
for academic adjustment.
PMID- 23156917
TI - Coping strategies: gender differences and development throughout life span.
AB - Development during life-span implies to cope with stressful events, and this
coping may be done with several strategies. It could be useful to know if these
coping strategies differ as a consequence of personal characteristics. This work
uses the Coping with Stress Questionnaire with this aim using a sample of 400
participants. Specifically, the effects of gender and age group (young people,
middle age and elderly), as well as its interaction on coping strategies is
studied. With regard to age, on one hand, it is hypothesised a decrement in the
use of coping strategies centred in problem solving and social support seeking as
age increases. On the other hand, the use of emotional coping is hypothesised to
increase with age. With respect to gender, it is hypothesised a larger use of
emotional coping and social support seeking within women, and a larger use of
problem solving within men. A MANOVA found significant effects for the two main
effects (gender and age) as well as several interactions. Separate ANOVAs allowed
us to test for potential differences in each of the coping strategies measured in
the CAE. These results partially supported the hypotheses. Results are discussed
in relation to scientific literature on coping, age and gender.
PMID- 23156918
TI - The impact of helping behavior on outgroup infrahumanization.
AB - Infrahumanization research has verified that in intergroup contexts, there is a
strong tendency to attribute secondary emotions, which are uniquely human, to the
ingroup, while limiting that attribution in outgroups. Experiments have shown it
to be as common as ingroup bias. However, it is not yet known what
characteristics may mitigate this trend. This paper presents two studies. The
first analyzes the impact of helping behavior on attributions of human traits to
two fictitious groups. The second study's objective was to determine if members
of the Spanish ingroup would infrahumanize an Ethiopian outgroup less when that
outgroup performs prosocial behavior towards another group. Infrahumanization was
determined by a lexical decision task, using the names of ingroup and outgroup
members as priming. The results demonstrate that describing a fictitious group in
altruistic terms increases their human profile (experiment one) and reduces
infrahumanization (experiment two).
PMID- 23156919
TI - Are they animals or machines? Measuring dehumanization.
AB - The present research deals with two forms of dehumanization: 1) denying uniquely
human attributes to others (seeing them as animals); 2) denying human nature to
others (seeing them as machines or automata). Studies 1 and 2 explored these two
forms of dehumanization, analyzing whether people associated their ingroup more
with human-related words (vs. animal- vs. machine-related words) than two
different outgroups. A paper and pencil procedure was used to find out which
words were associated with the surnames of the ingroup (Spaniards) or the
outgroup (Germans, Gypsies). Results showed that participants were more ready to
link ingroup than outgroup surnames to human words. They also linked more Gypsy
surnames to animal-related words and German surnames with machine-related words.
Studies 3 and 4 used the Implicit Association Test to analyze the same ideas and
replicated the results of Studies 1 and 2.
PMID- 23156920
TI - The dark and bright sides of self-efficacy in predicting learning, innovative and
risky performances.
AB - The objective of this study is to analyze the different role that efficacy
beliefs play in the prediction of learning, innovative and risky performances. We
hypothesize that high levels of efficacy beliefs in learning and innovative
performances have positive consequences (i.e., better academic and innovative
performance, respectively), whereas in risky performances they have negative
consequences (i.e., less safety performance). To achieve this objective, three
studies were conducted, 1) a two-wave longitudinal field study among 527
undergraduate students (learning setting), 2) a three-wave longitudinal lab study
among 165 participants performing innovative group tasks (innovative setting),
and 3) a field study among 228 construction workers (risky setting). As expected,
high levels of efficacy beliefs have positive or negative consequences on
performance depending on the specific settings. Unexpectedly, however, we found
no time x self-efficacy interaction effect over time in learning and innovative
settings. Theoretical and practical implications within the social cognitive
theory of A. Bandura framework are discussed.
PMID- 23156921
TI - Dynamic criteria: a longitudinal analysis of professional basketball players'
outcomes.
AB - This paper describes the fluctuations of temporal criteria dynamics in the
context of professional sport. Specifically, we try to verify the underlying
deterministic patterns in the outcomes of professional basketball players. We use
a longitudinal approach based on the analysis of the outcomes of 94 basketball
players over ten years, covering practically players' entire career development.
Time series were analyzed with techniques derived from nonlinear dynamical
systems theory. These techniques analyze the underlying patterns in outcomes
without previous shape assumptions (linear or nonlinear). These techniques are
capable of detecting an intermediate situation between randomness and
determinism, called chaos. So they are very useful for the study of dynamic
criteria in organizations. We have found most players (88.30%) have a
deterministic pattern in their outcomes, and most cases are chaotic (81.92%).
Players with chaotic patterns have higher outcomes than players with linear
patterns. Moreover, players with power forward and center positions achieve
better results than other players. The high number of chaotic patterns found
suggests caution when appraising individual outcomes, when coaches try to find
the appropriate combination of players to design a competitive team, and other
personnel decisions. Management efforts must be made to assume this uncertainty.
PMID- 23156922
TI - A comparative study on entrepreneurial attitudes modeled with logistic regression
and Bayes nets.
AB - Entrepreneurship research is receiving increasing attention in our context, as
entrepreneurs are key social agents involved in economic development. We compare
the success of the dichotomic logistic regression model and the Bayes simple
classifier to predict entrepreneurship, after manipulating the percentage of
missing data and the level of categorization in predictors. A sample of
undergraduate university students (N = 1230) completed five scales (motivation,
attitude towards business creation, obstacles, deficiencies, and training needs)
and we found that each of them predicted different aspects of the tendency to
business creation. Additionally, our results show that the receiver operating
characteristic (ROC) curve is affected by the rate of missing data in both
techniques, but logistic regression seems to be more vulnerable when faced with
missing data, whereas Bayes nets underperform slightly when categorization has
been manipulated. Our study sheds light on the potential entrepreneur profile and
we propose to use Bayesian networks as an additional alternative to overcome the
weaknesses of logistic regression when missing data are present in applied
research.
PMID- 23156923
TI - Reciprocity of temporary and permanent workers: an exploratory study in an
industrial company.
AB - The increasing use of temporary work prompts the need to understand to what
degree workers with this type of contract differ from permanent workers as to the
relationship they establish with the organization they work for. This study used
a sample of temporary workers (N = 78) and permanent workers (N = 196) within the
same company of electronics in Portugal. The results show that, regardless of the
type of contract, the perception of human resource practices was related to the
perception of psychological contract fulfillment by the company. Additionally and
according to the norm of reciprocity, we verified that when workers thought the
company was fulfilling its obligations they responded favorably showing more
affective commitment towards the company. However, we found differences between
these two groups of workers: for the permanent performance appraisal, training
and rewards were human resources practices that were significantly related to
psychological contract fulfillment, while for the temporary ones there weren't
any specific practices that had a significant relationship with that variable.
The practical implications of these findings for the management of temporary
workers are discussed.
PMID- 23156924
TI - The roles of constraint-based and dedication-based influences on user's continued
online shopping behavior.
AB - The objective of this study was to determine empirically the role of constraint
based and dedication-based influences as drivers of the intention to continue
using online shopping websites. Constraint-based influences consist of two
variables: trust and perceived switching costs. Dedication-based influences
consist of three variables: satisfaction, perceived usefulness, and trust. The
current results indicate that both constraint-based and dedication-based
influences are important drivers of the intention to continue using online
shopping websites. The data also shows that trust has the strongest total effect
on online shoppers' intention to continue using online shopping websites. In
addition, the results indicate that the antecedents of constraint-based
influences, technical bonds (e.g., perceived operational competence and perceived
website interactivity) and social bonds (e.g., perceived relationship investment,
community building, and intimacy) have indirect positive effects on the intention
to continue using online shopping websites. Based on these findings, this
research suggests that online shopping websites should build constraint-based and
dedication-based influences to enhance user's continued online shopping behaviors
simultaneously.
PMID- 23156925
TI - Social integration of Latin-American immigrants in Spain: the influence of the
community context.
AB - The main goal of this study is to analyze the degree to which several community
elements such as insecurity, discrimination and informal community support might
have an influence on the social integration of Latin-American immigrants, a group
at risk of social exclusion in Spain. Multivariate linear regression analyses
results showed that informal community support is positively related to social
integration whereas insecurity is negatively related. The statistical
relationship between discrimination and social integration disappears once levels
of informal community support are taken into account. A better understanding of
the factors that either promote or inhibit the social integration progress of
immigrant population is important to orientate public policies and intervention
programs that contribute to the adaptation of this population to the host
society.
PMID- 23156926
TI - Language use and stereotyping: the role of approach and avoidance motivation
goals.
AB - The use of more abstract language to describe expected behaviors as opposed to
unexpected behaviors has traditionally been considered a way of stereotype
maintenance. This tendency is known as linguistic expectancy bias. Two
experiments examined the influence of approach and avoidance motivational
orientations on the production of this linguistic expectancy bias. It was
predicted that approach strategic orientation is likely to describe expectancy
consistent behaviors at a higher level of linguistic abstraction than expectancy
inconsistent behaviors. In contrast, avoidance strategic orientation is likely to
describe both expectancy consistent behaviors and expectancy inconsistent
behaviors at a lower level of linguistic abstraction, thus facilitating the
disappearance of linguistic expectancy bias. Two experiments confirmed these
expectations, using strategic orientation manipulations based either on
communication goals or on motor action, and measuring linguistic abstraction
either on forced-choice answer format or on free descriptions. Implications for
the generalisation of linguistic expectancy bias are discussed.
PMID- 23156927
TI - On methods of access to the structure of social representations: the example of
Europe.
AB - The aim of this study is to identify the logic behind a range of statistical
methods used to reveal the structure of social representations. Subjects (N =
317) were asked to answer the following question: "For each category of European
person, please indicate which other European he would most like to have contact
with". The results of the similarity analysis lead us to the conclusion that
there is an ethnocentric bias, and reveal the central factor of the
representation. The representation obtained by factorial correspondence analysis
seems closer to current reality and enables us to understand the divisions that
have structured Europe and remained embedded in the subjects. Thus, the choice of
analytical method is not merely anecdotal, given that representations obtained
from the same data can vary immensely.
PMID- 23156928
TI - Social representations, correspondence factor analysis and characterization
questionnaire: a methodological contribution.
AB - The characterization questionnaire is inspired by Q-sort methodologies (i.e.
qualitative sorting). It consists in asking participants to give their opinion on
a list of items by sorting them into categories depending on their level of
characterization of the object. This technique allows us to obtain distributions
for each item and each response modality (i.e. characteristic vs. not chosen vs.
not characteristic). This contribution intends to analyze these frequencies by
means of correspondence factor analysis. The originality of this contribution
lies in the fact that this kind of analysis has never been used to process data
collected by means of this questionnaire. The procedure will be detailed and
exemplified by means of two empirical studies on social representations of the
good wine and the good supermarket. The interests of such a contribution will be
discussed from both methodological points of view and an applications
perspective.
PMID- 23156929
TI - Degree of proximity in the construction of social representations: the case of
intelligence.
AB - The present article is devoted to the empirical endeavor of studying the effect
of the degree of proximity, defined by specific socio-educational insertions, on
the organization of social representations of intelligence. A questionnaire was
answered by a sample of 752 participants belonging to five different social
categories with different degrees of proximity and knowledge about intelligence:
mothers, fathers, mother-teachers and non-parent students (psychology and science
students). The questionnaire included different topics, namely concerning the
concept of intelligence, its development and the effectiveness of teaching
procedures. Results show that the principles organizing the contents of
representations are linked to the personal involvement in intelligence, on which
subjects more or less implied take different positions. Results produced suggest,
therefore, that the content of representations is directly linked to the
activation of social roles and the salience of the object, reflecting the
functional character that the organization of representations has to specific
social dynamics.
PMID- 23156930
TI - Dispositional optimism is unidimensional or bidimensional? The Portuguese revised
Life Orientation Test.
AB - The aim of the study is to adapt and then discuss the appropriateness of the Life
Orientation Test as a one or two dimension scale. The research includes two
studies; one is composed of a sequential sample of 280 people with multiple
sclerosis, 71% female, and another includes a convenience sample of 615
individuals from the community, 51.1% female. Because the construct is built upon
a theoretical assumption that has one dimension, we examine the hypothesis of one
or two factor solutions through confirmatory factor analysis, and the two
dimension solution premise demonstrates better adjustment for both samples. The
other psychometric properties explored show appropriate results for the
Portuguese sample, and similar to the original ones; the Test therefore seems
appropriate for use in cross cultural studies. Based on our results, we discuss
whether the questionnaire is a one or two dimension instrument, concluding that
it appears appropriate to accept the recommendations of the original authors to
use it as a one-dimensional tool and, when necessary, to use both dimensions.
PMID- 23156931
TI - Personality traits and sick leave in workers diagnosed with nonorganic neck pain.
AB - Previous research has suggested that personality can influence the perception and
reporting of physical symptoms, such as pain. To assess the relationship between
the course of nonorganic neck pain and the individual's personality, we studied
the association between two indicators of neck pain prognosis, such as the
duration of sick leave associated with neck pain and sick leave recurrence, and
15 personality traits in a sample of 64 workers suffering from disabling neck
pain without any signs of physical abnormalities in the neck area. The TEA
Personality Test (TPT), a self-report instrument designed to evaluate personality
traits related to organizational behaviors, was used. Compared to the normative
data, the study sample obtained high scores in the Depression, Anxiety and
Emotional Instability scales, thus suggesting a personality profile primarily
characterized by high neuroticism-related scores. Controlling for age, gender,
and any rehabilitation undergone, we found a positive relationship between
Depression and the duration of sick leave (in weeks). Moreover, lower scores on
the TPT personality trait Dynamism and activeness were associated with higher
likelihood of sick leave recurrence. These findings highlight the need for
further research into the role played by personality at the onset and in the
maintenance of nonorganic neck pain. Furthermore, they suggest that a
complementary psychological approach may be useful to nonorganic neck pain
management.
PMID- 23156932
TI - Autonomy support, basic psychological needs and well-being in Mexican athletes.
AB - Based on Basic Needs Theory, one of the mini-theories of Self-determination
Theory (Ryan & Deci, 2002), the present study had two objectives: (a) to test a
model in the Mexican sport context based on the following sequence: perceived
coach autonomy support, basic psychological needs satisfaction, and psychological
well-being, and b) to analyze the mediational effect of the satisfaction of
perceived coach autonomy support on indicators of psychological well-being
(satisfaction with life and subjective vitality). Six hundred and sixty-nine
young Mexican athletes (Boys = 339; Girls = 330; M(age) = 13.95) filled out a
questionnaire assessing the study variables. Structural equations analyses
revealed that perceived coach autonomy support predicted satisfaction of the
basic psychological needs for autonomy, competence, and relatedness. Furthermore,
basic need satisfaction predicted subjective vitality and satisfaction with life.
Autonomy, competence and relatedness partially mediated the path from perceived
coach autonomy support to psychological well-being in young Mexican athletes.
PMID- 23156933
TI - Well-being and prejudice toward obese people in women at risk to develop eating
disorders.
AB - The literature has found that eating disorders (ED) patients usually have a
depression and anxiety diagnosis. However, not many investigations have studied
the relationship between ED and well-being. One of the main problems of patients
with ED is their body image. These individuals usually see themselves too big but
there are not many investigations that focus on how these patients see people
with real weight problems. For this reason in this study it is analyzed how women
in risk to develop ED see obese people. 456 female students were selected. It was
found that women with high scores in the different subscales of the Eating
Attitudes Test 26 (EAT-26; dieting, bulimia and oral control) had lower well
being (both subjective and psychological) and worse attitudes toward obese people
(measured with Antifat Attitudes Test, AFA, Beliefs About Obese People Scale,
BAOP, and Attitudes Toward Obese People Scale, ATOP) compared with women with low
scores in the EAT-26.
PMID- 23156934
TI - Quality of life and emotional distress among HIV-positive women during transition
to motherhood.
AB - The purpose of this preliminary study was to describe the quality of life (QOL)
and emotional distress during pregnancy and early postpartum, and to examine the
ability of psychopathological symptoms to predict QOL at early postpartum. A
sample of 75 pregnant women (31 HIV-positive and 44 HIV-negative) was assessed
during the second trimester of pregnancy and two to four days postpartum. QOL was
assessed with the WHOQOL-Bref. The emotional distress was assessed with the Brief
Symptom Inventory, and with the Emotional Assessment Scale. Seropositive women
reported increased negative emotional reactivity and lower scores in social
relationships and overall QOL during pregnancy than HIV-negative women. Both HIV
positive and HIV-negative women reported better QOL after the birth of their
child, when compared with the pregnancy period. Among HIV-positive women, lower
anxiety and depressive symptoms during pregnancy were, respectively, significant
predictors of better psychological QOL and overall QOL at early postpartum. Less
intense somatic symptoms predicted better physical QOL. Longitudinal assessment
of QOL and emotional status may provide potentially useful information for
tailoring psychological interventions in the maternity care of HIV-infected
women, during their transition to motherhood.
PMID- 23156935
TI - Portuguese adolescents: the importance of parents and peer groups in positive
health.
AB - The purpose of this study is to examine the influence of peer groups and parents
on adolescents' health. It was examined how communication relationships with peer
groups and parents affect youngsters life satisfaction, sadness, irritability,
being nervous, fear and troubles in falling asleep. The sample was comprised of
individuals that participated in the study in continental Portugal, integrating
the European study HBSC - Health Behavior in School - aged Children. The study
was made during January 2006 and included a total of 4,877 students attending the
6th, 8th and 10th grades from Portuguese public schools, with an average age of
14 years of age. The instrument used was the HBSC questionnaire. The results
showed that adolescents' health is influenced by their relationship with their
parents and peers. When the communication with both is easy, youngsters are more
satisfied with life and have less health negative symptoms. When compared with
peers, parents influence positively the adolescents' health.
PMID- 23156936
TI - Professionals' criteria for detecting and reporting child sexual abuse.
AB - Professionals who are likely to come into contact with children play an essential
role in the protection of children, thus we aimed to study the criteria they use
to identify and report child sexual abuse cases. Based on the Factorial Survey
design, we presented 974 Spanish (90%) and Latin American professionals from six
fields (Psychology, Social Services, Education, Health, Law and Security) with
hypothetical situations of sexual interaction with minors (systematically varying
the type of sexual act, the child's and the other person's sex and age, the use
of coercion and the type of strategy employed to involve the child), in order to
examine their perception of abuse and willingness to report. According to
results, the factors or criteria that most impact assessments are age asymmetry
and use of coercion. Specifically, professionals are significantly more likely to
perceive abuse and intend to report it if the other person involved in the
interaction is much older than the minor and/or uses a coercive strategy,
especially force, drugs or blackmail. Another relevant criterion is the type of
sexual act, since acts involving intercourse, digital penetration or oral sex are
significantly more likely to be deemed as abuse and reported.
PMID- 23156937
TI - Prediction of PTSD in police officers after six months--a prospective study.
AB - The aim of this prospective study was to explore the predictors for the
development of PTSD in police officers six months after encountering situations
of a potentially traumatic nature. Fifty-nine police officers were studied
immediately after the event (T1) and six months later (T2). At T2 PTSD was
assessed using the Structured Clinical Interview for DSM-IV (SCID-I). PTSD was
predicted by intrusions (Impact of Event Scale-Revised; IES-R), the impairment
scale (is), global assessment of functioning scale (GAF), gender, age and sense
of coherence scale (SOC). The diagnosis of an acute stress disorder (ASD) at T1
had a high specificity for identifying PTSD at T2. The strongest predictor for
the development of PTSD was found to be the factor intrusions. Contrary to our
expectations, age was not a significant predictive factor for PTSD. Thus, acute
stress disorder (ASD) and a high degree of intrusions experienced immediately
after a traumatic incident helped to identify early police officers at risk of
developing chronic PTSD.
PMID- 23156938
TI - What predicts retention on an in-prison drug treatment program?
AB - The effectiveness of treatments for substance use disorders is strongly related
to retention, since early dropout from treatment is associated with greater
likelihood of relapse. The purpose of this prospective, ex post facto study is to
analyze the effect of individual variables on retention in a treatment program
carried out in a prison drug-free unit. The Addiction Severity Index, motivation
and personality profile of fifty inmates were assessed on entry to the prison.
Inmates were monitored for a year to identify length of stay. RESULTS: Motivation
variables at intake play a vital role in the prediction of retention in a prison
drug-free unit; scores on the Aggressive-Sadistic and Narcissistic scales are
also strong predictors of treatment retention.
PMID- 23156939
TI - Impact of acceptance-based nursing intervention on postsurgical recovery:
preliminary findings.
AB - Research has shown that teaching individuals to experience pain and anxiety as
inevitable products of the actions they freely and responsibly undertake yields
healthier reactions to suffering. This preliminary study assesses whether a brief
acceptance-based psychological intervention along with the usual presurgical
protocol for a laparoscopic cholecystectomy will produce healthier reactions to
postsurgical pain, and will reduce anxiety, duration of postsurgical
hospitalization, and demand of analgesics. After admission, screening, and
consent procedures, we assessed pain and anxiety. Patients in the experimental
condition (n = 6) then received a brief acceptance-based nursing intervention
addressing the individual meaning of surgery, and including a metaphor and
defusion practice, along with routine care. Patients in the control condition (n
= 7) received routine care only. Twenty-four hr following the intervention,
surgery took place. Pain, anxiety, and patients' demand for analgesics were
assessed 24 hr or 48 hr after surgery. All six experimental patients, as compared
to three of seven control patients, demanded fewer analgesics and left the
hospital within 24 hr or 48 hr from surgery even in the presence of frequent
and/or intense pain. Anxiety slightly decreased in the experimental patients. The
brief acceptance-based intervention was effective in improving postsurgical
recovery. These preliminary findings support the potential of this type of
intervention as a cost-effective strategy to be implemented in the sanitary
context.
PMID- 23156940
TI - Effectiveness of rhythmic movement therapy for disordered eating behaviors and
obesity.
AB - The aims of the present study were: a) to examine associations between pre
treatment BMI, body dissatisfaction, perfectionism, alexithymia, and restraint,
emotional and external eating behaviour in obese patients; b) to analyze the
impact of the pre-treatment measures in psychological variables on the outcome of
cognitive-behavioral therapy (CBT) program; c) to test the effectiveness of
rhythmic movement therapy (RMT) in the treatment of disordered eating behaviors
and obesity with the CBT non-responders. At the first stage of treatment a total
of 104 patients (32 males and 72 females, mean age was 37.6 +/- 6.7 years) self
referred or referred by professionals to CBT weight management program were
selected at random. At the second stage 58 obese CBT-non-responders were randomly
divided among the continuing CBT individual treatment group and RMT group.
Control group was included. Results revealed that: a) significant associations
existed between pre-treatment BMI, external eating and two dimensions of
perfectionism, as well as between emotional and external eating and all
dimensions of perfectionism, alexithymia and body image dissatisfaction; b) pre
treatment means of psychological variables significantly impacted the CBT program
outcome; c). the efficacy of RMT approach for weight reduction as well as for the
improvement of psychological status for CBT-non-responders was confirmed.
PMID- 23156941
TI - Effectiveness of cognitive-behavioral treatment for major depressive disorder in
a university psychology clinic.
AB - Major Depressive Disorder (MDD) is the most prevalent mental disorder in our
environment, and one of the main causes of disability. While several empirically
supported treatments (ESTs) for MDD exist, some doubts have been cast on the
applicability--in time, components, and effectiveness--of these ESTs in routine
clinical practice. A few attempts have been made to contrast the effectiveness of
ESTs, but usually the precise components of the treatment developed are not
considered in detail. The purpose of this study is to analyze the components of
an EST-based treatment on a sample of 69 MDD cases from a University Psychology
Clinic, and to benchmark them against the results of published efficacy studies
on ESTs (behavioral activation, cognitive therapy, interpersonal therapy).
Results show that treatments delivered at this clinical facility are similar in
components, length, and effectiveness (in effect size, completers and improved
ratio) to the benchmarked studies. Cognitive restructuring is the most frequent
component of the delivered treatments. Therapy results show a 3.12 effect size,
and a 55.1% improved ratio over initial sample, an 80% of completers. Results and
limitations of the current study, especially those related to sample and center
characteristics, are discussed.
PMID- 23156942
TI - Validation of Children's Depression Scale in the Basque-speaking population.
AB - The aim of this study was to validate the Basque version of the CDS (Children's
Depression Scale, Lang & Tisher, 1978), one of the most widely used
questionnaires for the assessment of childhood depression, which has already been
proved to be a valid and reliable tool in different cultures. The questionnaire
was administered to a community sample of 886 participants (432 males and 454
females) aged between 8 and 16. A two-factor solution was obtained (Depressive
dimension and Positive Dimension), which accounted for 29.86 % of the variance.
Reliability with regard to internal consistency level and long-term stability was
good (alpha = .95 and .79; and R = .73 and .59 for Depressive and Positive
dimensions, respectively). Analysis of Differential Item Functioning with respect
to age and gender showed that 91% and 88% of the items, respectively, did not
present DIF. External validity evidence for the questionnaire was also obtained.
We consider that the present work offers researchers and professionals interested
in this area of study a valid and reliable tool for assessing depressive symptoms
in Basque-speaking children and adolescents.
PMID- 23156943
TI - When I don't like myself: Portuguese version of the Internalized Shame Scale.
AB - In the past two decades, there has been a growing theoretical and empirical
interest on the role of shame, namely internal shame, on the conceptualization of
human functioning and several interpersonal and emotional problems. The current
study explores the psychometric properties of the Portuguese version of the
Internalized Shame Scale (ISS), a self-report measure which assesses trait shame,
composed by an Internal Shame subscale, measuring internalized shame, and a Self
Esteem subscale. The factor structure, internal consistency, test-retest
reliability and convergent and discriminant validity for both subscales, are
presented, in a sample of 385 college students. The Principal Components Analyses
reveal that both Internal Shame and Self-Esteem subscales present a one
dimensional structure which explains, respectively, 48.54% and 57.7% of the
variance. The subscales present high internal consistency, with high Cronbach'
alphas (.95 and .85) and moderate to high item-total correlations. The two
subscales present an excellent temporal stability. Convergent and discriminant
validity of the subscales was corroborated through the moderate correlations with
a measure of shame and of social comparison, and through the low and moderate
correlations with the subscales depression, anxiety, and stress. The Portuguese
version of the ISS is a valid and reliable instrument to measure internalized
shame.
PMID- 23156944
TI - The Memory Failures of Everyday (MFE) test: normative data in adults.
AB - One approach to the study of everyday memory failures is to use multiple-item
questionnaires. The Memory Failures of Everyday (MFE) test is one of the most
frequently used in Spain. Our objective is to provide normative data from the MFE
in a sample of healthy, Spanish, adult participants for use in clinical practice.
The sample consists of 647 employees at a large company ranging in age from 19-64
years-old. Everyday memory failures were evaluated by means of the MFE with the
following response format: 0-2 (0 = never or rarely; 1 = occasionally, sometimes;
2 = frequently, often). RESULTS: Mean MFE = 15.25 (SD = 7.50), range 0-40.
Correlation with age: .133 (p = .001); and with years of education: - .059
(n.s.). A constant increase in MFE was not observed across age groups (F = 4, 59;
p = .003, eta2 = .02), but differences were revealed between the 19-29 and 40-49
age groups; no differences were observed between the remaining age groups. Only
slight differences between men and women occurred, the women's mean being
slightly higher than the men's, but the confidence intervals overlapped (F = 5,
71; p = .017, eta2 = .01). These results indicate that age, years of education,
and sex had no significant effects. In light of the above, the sample was viewed
as a whole when computing the percentiles reported here.
PMID- 23156945
TI - Measuring the desire for control: a Spanish version of Burger and Cooper's Scale.
AB - The following study will present findings on the validity of the adaptation of
the Burger and Cooper's Desirability of Control Scale into Spanish. Two samples
are present: the first involving 1,999 people to study their psychometric
properties. In the second sample, 111 people were included to estimate
test/retest reliability. Cultural adaptation was performed using the translation
& back-translation method. Item analysis, internal consistency and test/retest
reliability were assessed, then evidence of the validity of the internal
structure was determined by using exploratory and confirmatory factor analysis.
Subject recruitment was performed to gather the 1,999 subjects stratified by age,
gender quotas as designed in the sampling plan. Of the subjects, 51% were female,
average age of 45 years old (SD = 17.5). All items from the original scale were
understood correctly, while five items presented ceiling effect. Cronbach's alpha
= .736 and a test-retest correlation r = .713 were obtained. The factor structure
indicated the presence of four dimensions: forecast, autonomy, power and
influence and reactance which were reassured in the confirmatory analysis
(chi2/df = 4.805, CFI = .932, TLI = .954, RMSEA = .062). The basic dimensions of
the scale have shown to be stable and well-defined, though not perfect. The
scope, possible applications of the scale and further research are later proposed
and discussed.
PMID- 23156946
TI - School Motivation Questionnaire for the Portuguese population: structure and
psychometric studies.
AB - It is presented the structure and psychometric studies of the "School Motivation
Questionnaire". The SMQ is a self-report questionnaire with 101 items, organized
in sixteen scales that measure the students' goal orientations, the perceived
classroom goal structures, the perceived teacher's autonomy support and the use
of learning strategies. Twelve scales are adapted from the "Learning Climate
Questionnaire", "Perceptions of Instrumentality" and "Cuestionario a
Estudiantes". Four scales and five additional items are created new. The
psychometric studies rely on a convenience sample consisting of 9th and 12th
grade students (N = 485) of Portuguese schools. The factorial and construct
validity, verified through several exploratory factorial analyses to the data,
presents a final solution of six factors, labelled Strategies (F1), Teacher
Extrinsic Goals (F2), Student Extrinsic Goals, Externally Regulated (F3) Teacher
Intrinsic Goals (F4), Student Extrinsic Goals, Internally Regulated (F5), and
Student Intrinsic Goals (F6). The six-factor solution explains a significant
variance of the scale results (53.95%). Good coefficients of internal consistency
are obtained for all factors, never below (.858; F6). In sum there is strong
evidence to support the multi-dimensionality of SMQ, upholding that the data
obtained is exploratory and applies for future validation studies.
PMID- 23156947
TI - Development and validation of a measuring instrument for burnout syndrome in
teachers.
AB - This paper is part of a research done on Burnout Syndrome, and its objective is
to develop and validate an instrument for measuring the syndrome in Secondary
School teachers, taking as a principal starting point Maslach, Schaufeli, and
Leiter's theory (2001). After developing and testing the instrument on a sample
of 794 teachers in the Community of Madrid (Spain), we analyzed the reliability,
content and construct validity (the latter by means of Structural Equations
Models implemented with Software AMOS 7.0). The reliability analysis (alpha =
.911 for the total instrument; .849, .899 and .674 for the dimensions of
Exhaustion, Reduced Personal Accomplishment and Depersonalization respectively)
and the Confirmatory Factorial Analysis (CMIN/DF = 4.163, CFI = .904, RMSEA =
.60, PRATIO = .874) showed highly satisfactory results. The discrimination
coefficient scores for items in the final instrument ranged between .22 and .74.
Thus, the instrument presented combines the necessary technical characteristics
for it to be considered a valid and reliable tool for measuring the syndrome.
PMID- 23156948
TI - Measuring autonomy support in university students: the Spanish version of the
Learning Climate Questionnaire.
AB - The goals of this research were to translate and analyze the psychometric
properties of the Learning Climate Questionnaire (LCQ) and to develop a short
form. The LCQ is a 15-item self-report measure that assesses autonomy support in
educational settings. A total of 422 students (60 men and 362 women) took part in
this study. Results showed evidence of construct validity and adequate
reliability for the LCQ. The short form consists of five items that showed sound
psychometric properties. Results of Pearson correlation and Gower index showed
high agreement between the long and short forms. In conclusion, both forms can be
considered as preliminary versions of the original questionnaire to assess
autonomy support in educational settings.
PMID- 23156949
TI - School Social Behavior Scales: an adaptation study of the Portuguese version of
the social competence scale from SSBS-2.
AB - This study analyses the psychometric proprieties of a Portuguese version of the
social competence scale from the School Social Behavior Scales (SSBS-2, Merrell,
2002). It is a rating instrument of children and adolescents behavior, to be used
by teachers and other school personnel. This scale includes 3 subscales: self
management/compliance, peer relations and academic behavior. In our first sample,
175 teachers rated 344 students from grade 1 through 12. On the second sample 13
teachers rated 251 3rd and 4th grades students. The results from the Portuguese
adaptation support the multidimensional structure of the social competence scale
from the SSBS-2, although an alternative model demonstrated a better fit to the
data than the model originally proposed by the author. The scale showed good
internal consistency and good intercorrelations between subscales, as well as
between subscales and the total scale. The final model was well replicated in the
second sample. These results encourage us to pursue the SSBS-2 Portuguese
adaptation, in order to provide a useful and validated instrument for the
assessment of social competence and for educational interventions.
PMID- 23156950
TI - Spanish version of the Time Management Behavior Questionnaire for university
students.
AB - The main objective of the study is to analyze the psychometric properties and
predictive capacity on academic performance in university contexts of a Spanish
adaptation of the Time Management Behavior Questionnaire. The scale was applied
to 462 students newly admitted at the Universitat de Valencia in the 2006-2007
school year. The analyses performed made it possible to reproduce the factorial
structure of the original version of the questionnaire with slight modifications
in the ascription of various items. The underlying factorial structure includes
four interrelated dimensions (Establishing objectives and priorities, Time
management tools, Perception of time control and Preference for disorganization),
which present satisfactory levels of reliability and an adequate convergent
validity with the Time management subscale of the Motivated Strategies for
Learning Questionnaire. The scores on the dimensions of time management show
significant levels of association with academic performance in the first year of
university studies, especially highlighting the predictive capacity of the
subscale dealing with the Establishment of objectives and priorities. These
results show the reliability and validity of this adaptation of the scale for
evaluating how the students manage their academic time, and predicting their
performance in the year they initiate the degree program, thus aiding in the
development of intervention proposals directed towards improving these skills.
PMID- 23156951
TI - Spanish version of the Positive Expectancies for Drinking and Driving for Youth.
AB - In most developed countries, motor vehicle accidents are a leading cause of death
among young people, and a large proportion of motor vehicle accidents are alcohol
related. In Spain there are no currently available instruments for assessing
positive expectancies related to drinking and driving behavior. Attempting to
modify these expectancies may be an effective prevention approach, so there is a
need for a valid and reliable scale to measure the construct. The aims of the
present study were to translate, culturally adapt, and examine the psychometric
properties of a Spanish-language version of the Positive Expectancies for
Drinking and Driving for Youth (PEDD-Y) in a sample of Spanish young adults. A
total of 352 college students with drivers licenses were recruited at a
university in southeast Spain. We examined the factor structure, psychometric
properties (reliability and validity) and temporal stability of the Spanish
version of the PEDD-Y among Spanish young adult drivers. Findings indicated that
the Spanish version of the PEDD-Y demonstrated satisfactory psychometric
properties and was shown to significantly predict lifetime prevalence and future
intentions to drink and drive as well as riding with a drunk driver. The
Convenience factor performed with the most consistent reliability and predictive
validity. Limitations and future research questions are discussed.
PMID- 23156952
TI - A revised Thai Multi-Dimensional Scale of Perceived Social Support.
AB - In order to ensure the construct validity of the three-factor model of the Multi
dimensional Scale of Perceived Social Support (MSPSS), and based on the
assumption that it helps users differentiate between sources of social support,
in this study a revised version was created and tested. The aim was to compare
the level of model fit of the original version of the MSPSS against the revised
version--which contains a minor change from the original. The study was conducted
on 486 medical students who completed the original and revised versions of the
MSPSS, as well as the Rosenberg Self-Esteem Scale (Rosenberg, 1965) and Beck
Depression Inventory II (Beck, Steer, & Brown, 1996). Confirmatory factor
analysis was performed to compare the results, showing that the revised version
of MSPSS demonstrated a good internal consistency--with a Cronbach's alpha of .92
for the MSPSS questionnaire, and a significant correlation with the other scales,
as predicted. The revised version provided better internal consistency,
increasing the Cronbach's alpha for the Significant Others sub-scale from 0.86 to
0.92. Confirmatory factor analysis revealed an acceptable model fit: chi2 128.11,
df 51, p < .001; TLI 0.94; CFI 0.95; GFI 0.90; PNFI 0.71; AGFI 0.85; RMSEA 0.093
(0.073-0.113) and SRMR 0.042, which is better than the original version. The
tendency of the new version was to display a better level of fit with a larger
sample size. The limitations of the study are discussed, as well as
recommendations for further study.
PMID- 23156953
TI - A method to analyse measurement invariance under uncertainty in between-subjects
design.
AB - In this research we have introduced a new test (H-test) for analyzing scale
invariance in between group designs, and considering uncertainty in individual
responses, in order to study the adequacy of disparate rating and visual scales
for measuring abstract concepts. The H-test is easy to compute and, as a
nonparametric test, does not require any a priori distribution of the data nor
conditions on the variances of the distributions to be tested. We apply this test
to measure perceived service quality of consumers of a sports services. Results
show that, without considering uncertainty, the 1-7 scale is invariant, in line
with the related works regarding this topic. However, de 1-5 scale and the 1-7
scale are invariant when adding uncertainty to the analysis. Therefore, adding
uncertainty importantly change the conclusions regarding invariance analysis.
Both types of visual scales are not invariant in the uncertainty scenario.
Implications for the use of rating scales are discussed.
PMID- 23156954
TI - Behavioral regulation assessment in exercise: exploring an autonomous and
controlled motivation index.
AB - The main purpose of this study was to examine the psychometric properties of the
Portuguese version of the Behavioral Regulation in Exercise Questionnaire (BREQ
2) and to test the hypothesis that the different types of behavioral regulation
can be combined on a single factor to assess autonomous and controlled
motivation. Data were collected from 550 members of private fitness centres who
ranged in age from 14 to 69 years. The analysis supported an 18-item, 5-factor
model after excluding one item (S-B chi2 = 221.7, df = 125, p = .000, S-B chi2/df
= 1.77; SRMR = .06; NNFI = .90; CFI = .92; RMSEA = .04, 90% CI = .03-.05).
However, the analysis also revealed a lack of internal consistency. The results
of a hierarchical model based on 2 second-order factors that reflected controlled
motivation (external and introjected regulation) and autonomous motivation
(identified and intrinsic regulation) provided an acceptable fit to the data (S-B
chi2 = 172.6, df = 74, p = .000, S-B chi2/df = 2.33; SRMR = .07; NNFI = .90; CFI
= .92; RMSEA = .05, 90% CI = .04-.06), with reliability coefficients of .75 for
controlled motivation and .76 for autonomous motivation. The study findings
indicated that when item 17 was excluded, the Portuguese BREQ-2 was an
appropriate measure of the controlled and autonomous motivation in exercise.
PMID- 23156955
TI - Adaptation of the Athlete Burnout Questionnaire in a Spanish sample of athletes.
AB - In this paper, we offer a general version of the Spanish adaptation of Athlete
Burnout Questionnaire (ABQ) designed to measure the syndrome of burnout in
athletes of different sports. In previous works, the Spanish version of ABQ was
administered to different samples of soccer players. Its psychometric properties
were appropriate and similar to the findings in original ABQ. The purpose of this
study was to examine the generalization to others sports of the Spanish
adaptation. We started from this adaptation, but we included three alternative
statements (one for each dimension of the questionnaire), and we replaced the
word "soccer" with the word "sport". An 18-item version was administered to a
sample of 487 athletes aged 13 and 29 years old. Confirmatory factor analyses
replicated the factor structure, but two items modification were necessary in
order to obtain a good overall fit of the model. The internal consistency and
test-retest reliability of the questionnaire were satisfactory.
PMID- 23156956
TI - Tornados and terrorists.
PMID- 23156957
TI - The burden of disaster: Part I. Challenges and opportunities within a child's
social ecology.
AB - Child development and adaptation are best understood as biological and
psychological individual processes occurring within the context of
interconnecting groups, systems, and communities which, along with family,
constitute the child's social ecology. This first of two articles describes the
challenges and opportunities within a child's social ecology consisting of Micro
, Meso-, Exo-, and Macrosystems. The parent-child relationship, the most salient
Microsystem influence in children's lives, plays an influential role in
children's reactions to and recovery from disasters. Children, parents, and other
adults participate in Mesosystem activities at schools and faith-based
organizations. The Exosystem--including workplaces, social agencies,
neighborhood, and mass media--directly affects important adults in children's
lives. The Macrosystem affects disaster response and recovery indirectly through
intangible cultural, social, economic, and political structures and processes.
Children's responses to adversity occur in the context of these dynamically
interconnected and interdependent nested environments, all of which endure the
burden of disaster Increased understanding of the influences of and the
relationships between key components contributes to recovery and rebuilding
efforts, limiting disruption to the child and his or her social ecology A
companion article (R. L. Pfefferbaum et al., in press) describes interventions
across the child's social ecology.
PMID- 23156958
TI - Church attendee help seeking priorities after Hurricane Katrina in Mississippi
and Louisiana: a brief report.
AB - After a disaster, survivors find themselves seeking many types of help from
others in their communities. The purpose of this exploratory study was to assist
in mental health service planning by determining the type and priority of support
services sought by church attendees after Hurricane Katrina. Surveys were given
to church attendees from two Mississippi coast and four New Orleans area churches
that were directly affected by Hurricane Katrina participants were asked to
review a list of 12 potential sources of help and were asked to rank the items
chronologically from whom they had sought help first after Hurricane Katrina.
Overall, participants sought out assistance from informal social networks such as
family and friends first, followed by governmental and clergy support. This study
also showed there may be differences in help-seeking behaviors between church
attendees in more urban areas versus church attendees in more rural areas.
Moreover, findings highlighted that very few church attendees seek out mental
health services during the initial impact phase of a disaster. Since timely
engagement with mental health services is important for resolving trauma,
strategies that link professional mental health services with clergy and
government resources following a disaster could improve the engagement with
mental health professionals and improve mental health outcomes. Disaster mental
health clinical implications and recommendations are offered for psychologists
based on these findings.
PMID- 23156959
TI - The influence of indirect collective trauma on first responders' alcohol use.
AB - Previous research has suggested increased risk for negative outcomes such as
increased alcohol use among first responders who are involved with the response
to a community disaster; however it is not clear how indirect exposure to a
critical incident impacts first responders. This work examined the impact of
secondary or indirect trauma on changes in alcohol use among urban firefighters
who were not directly involved in the response to a large scale community-level
disaster. Firefighters enrolled in larger trial of health outcomes whose
interview period coincided with the crash of a commercial airplane were the basis
for the current report. Aggregate level data on changes in alcohol consumption
for these firefighters were examined pre- and post-incident. There was a
significant increase in alcohol use following the critical incident. This
increase did not occur immediately; it was observed within several days and
peaked about 8 days post-incident. Post-hoc analyses revealed that the increased
alcohol consumption persisted for several months, finally returning to pre
incident levels by 8 months post-incident. Indirect trauma effects, likely
operationalized in part through the "brotherhood" of the firefighters, clearly
placed firefighters at risk for negative outcomes following a disaster.
Intervention/prevention efforts aimed at distress reduction among first
responders should not solely focus on responders with direct involvement in a
disaster.
PMID- 23156960
TI - The effectiveness of cumulative stress debriefings with law enforcement
personnel.
AB - This article describes an intervention based on the Mitchel and Everly (1995)
model of Critical Incident Stress Management, yet used to address the cumulative
stress associated with being a police officer. This intervention occurred for
eight weeks with thirty-eight police officers, while on duty. Half of this group
met once a week as part of the treatment condition. There was no statistical
difference between the control and treatment group. These officers viewed the
intervention as helpful and reported that it should continue, which it did with
one of the treatment groups. Implications for addressing the psychological needs
of police officers and for future research are discussed.
PMID- 23156961
TI - Behind the blue shadow: a theoretical perspective for detecting police suicide.
AB - Police officers are at increased risk for suicide. Reluctance by this population
to self-report suicidal thoughts requires detection on a different level. Based
on existing theory, this paper discusses a possible alternative method for
detecting suicidal tendencies among police officers: the suicide Implicit
Association Test (IAT). The IAT measures the implicit strength of cognitive
identification with death opposed to life. Previous work has demonstrated that a
cognitive identification with death over life is associated with both suicide
attempts and completions. The clinical application of implicit cognitions, along
with other proven clinical measures, may be of value in detecting suicide
ideation in police officers or other high suicide risk groups who are hesitant to
explicitly report suicidal thoughts. More research is needed to help clarify the
clinical usefulness of the IAT and its validity over time.
PMID- 23156962
TI - Hostage (crisis) negotiation: the potential role of negotiator personality,
decision-making style, coping style and emotional intelligence on negotiator
success.
AB - This article explores the potential role of hostage negotiator characteristics
and the impact of psychological constructs on negotiator success. It explores the
role of Personality, Decision-Making Style, Coping Style, Cognitive Coping Style
and Emotion Regulation and Emotional Intelligence within high stress environments
and occupations. The findings suggest that certain individual traits and
characteristics may play a role in negotiator success, via the mediation of
specific styles, which are conducive to effective crisis negotiation skills. It
is proposed that these findings have application within the field of
hostage/crisis negotiation in the format of guidance regarding the recruitment
and selection of hostage negotiators and the identification of potential training
needs within individual negotiators in order to maximize their efficacy within
the field. In line with this, it is argued that a psychometric tool that assesses
these constructs is developed in order to aid the process of hostage negotiation
selection.
PMID- 23156963
TI - Orofacial myofunctional therapy: why now?
PMID- 23156964
TI - Technology is here to stay.
PMID- 23156965
TI - Masseter and temporalis excursive hyperactivity decreased by measured anterior
guidance development.
AB - The purpose of this study was to determine if a statistically significant
reduction in muscle activity (p<0.05) occurs when prolonged disclusion time (>0.4
sec/excursion) is shortened to <0.4 sec/excursion with the Immediate Complete
Anterior Guidance Development (ICAGD) enameloplasty. Forty-five symptomatic,
fully informed subjects (29 female, 16 male) had their right and left disclusion
times recorded with T-Scan III, while simultaneously, the bilateral masseter and
anterior temporalis muscle activity was recorded electromyographically with
BioEMG III (n=180 muscles). This recording was done twice, once pretreatment and
again posttreatment (same day) after undergoing the ICAGD enameloplasty on the
same day without changing electrodes. The Student's paired t-test was utilized to
detect any significant change in the muscle activity levels between the pre- and
posttreatment lateral excursive muscle contractions. Highly significant
reductions were found in all four muscles' activities after shortening the
pretreatment prolonged disclusion time to less than 0.4 seconds (p<0.0014); after
Bonferroni correction (p<0.006). When properly performed, such that the
posttreatment disclusion time is <0.4 sec/excursion, the ICAGD enameloplasty
predictably reduces excursive muscle activity levels in the bilateral anterior
temporalis and masseter muscles. Excursive muscle hyperactivity can be a source
of lactic acid accumulation, muscular ischemia, and chronic myalgic
temporomandibular joint dysfunction (TMD) symptoms. The ICAGD enameloplasty
significantly reduces excursive muscle contractions after completion of the first
ICAGD treatment session.
PMID- 23156966
TI - Assessment of the reliability and repeatability of landmarks using 3-D
cephalometric software.
AB - The aim of this study was to analyze the reliability and repeatability of
identification landmarks using 3-D cephalometric software. Ten orthognathic
patients were selected for this study and underwent the following protocol: 1.
radiographic evaluation (CBCT technique); 2. stone casts; 3. photos; and 4. 3-D
cephalometric evaluation. Twenty-one hard tissue landmarks and 14 cephalometric
measurements were taken three times (T1, T2, and T3) on each patient, with an
interval of one week by two experts in orthodontics (A, B). Standard deviation
and Pearson's correlation coefficient were calculated to evaluate intra- and
inter-observer repeatability. The results showed a strong correlation for both
intra- and inter-observer Pearson's correlation coefficient (>0.7). The current
preliminary study showed that the reliability and repeatability of the
identification landmarks were very high if the 3-D cephalometric landmarks are
defined correctly in the three planes of the space. Further evaluation is
necessary to better define the 3-D cephalometric system.
PMID- 23156967
TI - Low level laser therapy as an adjunctive technique in the management of
temporomandibular disorders.
AB - The purpose of this study was to assess the effect of low level laser therapy on
subjects with intra-articular temporomandibular disorders (IA-TMD), and to
quantify and compare severity of signs and symptoms before, during, and after the
laser applications. The sample consisted of 45 subjects randomly divided into
three groups (G) of 15 subjects each: G-I: 15 individuals with IA-TMD submitted
to an energy dose of 52.5 J/cm2; G-II: dose of 105.0 J/cm2; and G-III: placebo
group (0 J/cm2). In all groups, the applications were performed on condylar
points on the masseter and anterior temporalis muscles. Two weekly sessions were
held for five weeks, totaling 10 applications. The assessed variables were:
mandibular movements and painful symptoms evoked by muscle palpation. These
variables were measured before starting the study, then immediately after the
first, fifth, and tenth laser application, and finally, 32 days after completing
the applications. The results showed that there were statistically significant
differences for G-I and G-II at the level of 1% between the doses, as well as
between assessments. Therefore, it was concluded that the use of low level laser
increased the mean mandibular range of motion and reduced painful symptoms in the
groups that received effective treatment, which did not occur in the placebo
group.
PMID- 23156968
TI - Sequential analysis of head movement during mandibular open-close movements in
TMD patients with disc displacement with reduction.
AB - This study examined relationships between starting points of head and mandibular
movements in 11 female control subjects and 10 TMD patients showing disc
displacement with reduction during consecutive open-close movements, using a six
degree-of-freedom measuring device. During the first mandibular opening cycle, in
the TMD group, head movement was significantly preceded in relation to mandibular
movement when compared with the control group, and major differences in onset
were seen between maximum and minimal values at the beginning of mandibular
movements. After the second cycle, significant differences in starting points
were not evident. In TMD patients showing disc displacement with reduction, in
the first cycle, at the commencement of opening movements, it is proposed that
the head precedes the mandible in order to compensate for irregular condylar
movements, and the degree of the condylar movement irregularity might affect the
onset relation between the head and the mandible.
PMID- 23156969
TI - Is low level laser effective for the treatment of orofacial pain?: A systematic
review.
AB - The aim of this study was to assess the effectiveness of low level laser therapy
(LLLT) as a treatment for orofacial pain considering the methodology of the
studies. PubMed (1983-2009) and one conference proceeding were searched. Studying
quality was assessed using a validated instrument. A high-quality score was
defined as high or low. Outcomes were defined as either positive (+), neutral
(0), or negative (-). Thirty-three studies met inclusion criteria. The best
evidence synthesis method was used to formulate outcome of LLLT for each type of
control group. LLLT vs. placebo pooling revealed high-quality trials in three of
eight positive studies. In LLLT vs. other active treatment pooling, two high
quality studies out of nine neutral trials were found. Quality of the trial was
not significantly associated with neutral results (p=0.05). Only limited evidence
indicated that LLLT is more effective than placebo, sham laser, and other active
treatments.
PMID- 23156970
TI - Degenerative changes in rat condylar cartilage induced by non-matching occlusion
created by scattered orthodontic teeth-moving.
AB - The effect of occlusion on the temporomandibular joint (TMJ) is debated. By
inserting rubber-bands that were replaced by self-curing resin one week later,
the left maxillary and the right mandibular first-molars were moved and kept
mesially in Sprague-Dawley (SD) rats in both experimental I (EXP-I) and II (EXP
II) groups, aiming to establish a non-matching cusp-to-fossa occlusal relation.
Four weeks later, the left maxillary and the right mandibular third-molars were
moved and kept distally in the EXP-II group. Degenerative changes, typically as a
cell-free area, were observed in TMJs of the EXP groups. Binary logistical
analysis indicated that the odds ratio of EXP group, EXP-II vs. EXP-I, on the
incidence of a cell-free area, was 2.8 (p=.036). Time point, gender, and side did
not have such effects (p>0.05). The results indicate that the persistence of more
scattered non-matching cusp-to-fossa occlusion is more harmful to the condylar
cartilage in terms of the incidence of degenerative changes.
PMID- 23156971
TI - The use of electrognathography in jaw movement research: a literature review.
AB - The measurement of mandibular movements is a complex task that can be simplified
through the use of electrognathography (EGN), an examination that can be applied
as an auxiliary method for the diagnosis or follow-up of the evolution of
specific therapeutics applied to the stomatognathic system. The aim of the
present study was to review the literature pertaining to the use of EGN as a
method for monitoring jaw movements in the research and treatments related to the
stomathognathic system. A literature review was made by searching for articles in
PubMED, MEDLINE (1997-2010), MEDLINE (1966-1996), LILACS, Ovid, BBO and SciELO
databases. In this systematic review, 373 articles were found, of these, 23
articles were selected. The study concluded that EGN can be used with advantages
in varied clinical situations, although it is a technique still not widely
applied.
PMID- 23156972
TI - Low level laser therapy for the treatment of temporomandibular disorders: a
systematic review of the literature.
AB - The authors performed a review of the literature to evaluate the efficacy of low
level laser therapy (LLLT) for the treatment of temporomandibular disorders
(TMD). Selection criteria included: 1) human subjects, 2) articles written in
English, and 3) randomized placebo-controlled trials. Evaluation was performed
according to the CONSORT 2010 criteria. A total of 14 articles were included in
the review. Studies varied considerably in terms of methodological design,
particularly regarding the site of application of the laser beam, the number of
applications performed, their duration, the laser beam features (wavelength,
frequency, output, dosage), and outcome measures. The outcome of the trials was
controversial and not particularly related to any features of the laser beam, to
the number of laser applications, and their duration. Based on the results of
this review no definitive conclusions can be drawn on the efficacy of LLLT for
the treatment of TMD. Many methodological differences among the studies,
especially regarding the number and duration of laser applications and
characteristics of the laser beam (wavelength, frequency, output), do not allow
for standardized guidelines for effective treatment with LLLT. The only
indication seems to be that LLLT is probably more effective for the treatment of
TMJ disorders, and less effective for the treatment of masticatory muscle
disorders.
PMID- 23156973
TI - Hematologic and plasma biochemical values of hyacinth macaws (Anodorhynchus
hyacinthinus).
AB - The hyacinth macaw (Anodorhyncus hyacinthinus), considered the largest psittacine
bird species in the world, is an endangered species, with a remaining population
of approximately 6500 birds in the wild. To establish hematologic and plasma
biochemical reference ranges and to verify differences related to sex, samples
from 29 hyacinth macaws (14 males, 15 females) were obtained from birds
apprehended from illegal wildlife trade and subsequently housed at the Sorocaba
Zoo, Brazil. No significant differences in hematologic or plasma biochemical
values were found between females and males. Compared with published reference
values, differences were found in mean concentrations of total red blood cell
count, corpuscular volume, corpuscular hemoglobin level, total white blood cell
count, aspartate aminotransferase level, creatine kinase concentration, alkaline
phosphatase concentration, and phosphorus level. Baseline hematologic and plasma
biochemical ranges were established, which may be useful as reference values for
clinicians working with this endangered species in captivity or rehabilitation
centers.
PMID- 23156974
TI - Sedation and physiologic response to manual restraint after intranasal
administration of midazolam in Hispaniolan Amazon parrots (Amazona ventralis).
AB - Administration of intranasal midazolam (2 mg/kg) was evaluated for sedation and
effects on cloacal temperature, respiratory rate, and heart rate in manually
restrained Hispaniolan Amazon parrots (Amazona ventralis). Adult parrots (n=9)
were administered either midazolam (2 mg/kg) or an equal volume of saline
solution intranasally before a 15-minute manual restraint in a complete crossover
study. Respiratory rate and sedation scores were recorded before and during
capture and during and after 15 minutes of manual restraint. Heart rate and
cloacal temperature were recorded during manual restraint. After restraint, the
parrots received intranasal flumazenil (0.05 mg/kg) or an equal volume of saline
solution, and the recovery time was recorded. In those birds that received
midazolam, sedation was observed within 3 minutes of administration, and
vocalization, flight, and defense responses were significantly reduced during
capture. During manual restraint, the mean rate of cloacal temperature increase
was significantly slower and remained significantly lower in birds that received
midazolam compared with controls. Mean respiratory rates were significantly lower
for up to 12 minutes in parrots that received midazolam compared with those
receiving saline solution. Flumazenil antagonized the effects of midazolam within
10 minutes. No overt clinical adverse effects to intranasal midazolam and
flumazenil administration were observed. Further studies on the safety of
intranasal midazolam and flumazenil in this species are warranted.
PMID- 23156975
TI - Effects of ultracentrifugation on plasma biochemical values of prefledged wild
peregrine falcons (Falco peregrinus) in northeastern Illinois.
AB - Centrifugation is performed on whole blood samples to obtain serum or plasma for
biochemical analysis. Although blood samples centrifuged in a microhematocrit
tube may maximize recovery of plasma from small-volume samples, plasma
biochemical values from such samples have been implicated as causing erroneous
results. To compare blood biochemical values obtained by microhematocrit
centrifugation and centrifugation with a commercial tilt-rotor machine, blood
samples were collected from peregrine falcon (Falco peregrinus) eyases aged 32-40
days (n=51). The samples were separated into 2 equal aliquots with 1 aliquot
centrifuged in a tilt-rotor machine and the other aliquot ultracentrifuged in
microhematocrit tubes. Separated plasma from both processes was sent to a
commercial veterinary reference laboratory for routine clinical biochemical
analysis. No significant differences were found in the biochemical results of the
paired samples by the 2 centrifugation methods. These results show that the
centrifugation method has no effect on the plasma quality for biochemical
analysis in young peregrine falcons.
PMID- 23156976
TI - The detection of avian bornavirus within psittacine eggs.
AB - Avian bornavirus (ABV) is a known cause of proventricular dilatation disease in
parrots and encephalitis in waterfowl and is a significant cause of both
morbidity and mortality in captive birds. Transmission is thought to occur
primarily by the fecal-oral route. In an aviary setting, controlling the disease
involves a thorough understanding of the complete transmission cycle, including
determining whether vertical transmission occurs. In this study, vertical
transmission of ABV was evaluated by using 61 eggs obtained from birds in 2
aviaries where proventricular dilatation disease was prevalent, and the presence
of ABV had been confirmed by fecal reverse transcription-polymerase chain
reaction by using a primer set designed to detect ABV M protein. The contents of
these eggs were then tested for the presence of ABV RNA. Of the eggs tested, 10
were determined to contain ABV RNA. These eggs ranged from apparently nonviable
to those that contained developing embryos. ABV was detected in the brain tissue
of 2 embryos. It remains to be proven that infected chicks can hatch from these
eggs to complete the vertical transmission cycle; however, these findings suggest
that vertical transmission of ABV may occur.
PMID- 23156977
TI - Nutritional levels of diets fed to captive Amazon parrots: does mixing seed,
produce, and pellets provide a healthy diet?
AB - Poor nutrition is a serious problem in captive psittacine birds. Seed-based diets
are known to contain excess fat, low calcium:phosphorus ratios, and other
nutrient deficiencies, whereas many consider nutritionally superior, formulated
diets to be monotonous. As a result, many bird owners feed a mixture of seed,
produce, and formulated diet. However, the nutritional contents of such mixed
diets have rarely been evaluated. In this study, we describe the nutrient
contents of diets consumed by 7 adult (>6 years old), captive Amazon parrots
offered produce (50% fresh weight), formulated diet (25%), and seed (25%). Diets
consumed were deficient in calcium, sodium, and iron and contained more than the
recommended amount of fat. In addition, the birds chose foods that exacerbated
these imbalances. Birds offered low-seed diets (60% pellet, 22% produce, 18%
seed, wet weight) consumed diets with more fat than recommended but acceptable
levels of calcium and all other nutrients measured, as well as acceptable
calcium:phosphorus ratios. This suggests that small quantities of seeds may not
result in nutritionally imbalanced diets. Birds fed 75% formulated diet and 25%
produce consumed diets within the recommendations for nearly all measured
nutrients, demonstrating that owners of psittacine birds should be encouraged to
supplement manufactured diets with low energy-density, fresh produce items to
provide stimulation and foraging opportunities without fear of causing major
nutritional imbalances.
PMID- 23156978
TI - Pharmacokinetics of nebulized terbinafine in Hispaniolan Amazon parrots (Amazona
ventralis).
AB - Aspergillosis is one of the most difficult diseases to treat successfully in
avian species. Terbinafine hydrochloride offers numerous potential benefits over
traditionally used antifungals for treatment of this disease. Adding nebulized
antifungals to treatment strategies is thought to improve clinical outcomes in
lung diseases. To determine plasma concentrations of terbinafine after
nebulization, 6 adult Hispaniolan Amazon parrots were randomly divided into 2
groups of 3. Each bird was nebulized for 15 minutes with 1 of 2 terbinafine
solutions, one made with a crushed tablet and the second with raw drug powder.
Blood samples were collected at baseline and at multiple time points up to 720
minutes after completing nebulization. Plasma and nebulization solutions were
analyzed by high-performance liquid chromatography. The terbinafine concentration
of the solution made with a crushed tablet (0.87 +/- 0.05 mg/mL) was
significantly lower than was that made with raw powder (1.02 +/- 0.09 mg/mL).
Plasma concentrations of terbinafine did not differ significantly between birds
in the 2 groups. Plasma terbinafine concentrations in birds were maintained above
in vitro minimum inhibitory concentrations for approximately 1 hour in birds
nebulized with the crushed tablet solution and 4 hours in birds nebulized with
the raw powder solution. Higher concentrations of solution, longer nebulization
periods, or more frequent administration are likely needed to reach therapeutic
plasma concentrations of terbinafine for clinically relevant periods in
Hispaniolan Amazon parrots.
PMID- 23156979
TI - Implantation of a titanium partial limb prosthesis in a white-naped crane (Grus
vipio).
AB - A female white-naped crane (Grus vipio) was presented with an open, oblique
fracture of the distal right tarsometatarsus and concomitant vascular and nerve
damage. Conventional fracture fixation repairs failed, which led to implantation
of a custom titanium limb prosthesis. After subsequent revisions with 2 different
prosthetic devices, limb function was ultimately restored but a later yolk
embolism caused a circulatory compromise in the opposite leg, which necessitated
euthanasia. Histopathologic results revealed limited ingrowth of bone into the
porous coated implant, which indicated that a limb prosthesis may provide salvage
for long-legged, heavy-bodied birds with fractures of the tarsometatarsus.
PMID- 23156980
TI - Ingluviotomy tube placement for lead-induced crop stasis in the California condor
(Gymnogyps californianus).
AB - Six free-flying California condors (Gymnogyps californianus) were diagnosed with
acute lead toxicosis that caused crop distension and stasis. Between January 2006
and January 2007, the birds were referred to the Phoenix Zoo in Arizona for
emergency treatment. In 5 birds, an ingluviotomy was performed to place a feeding
tube from the crop to the proventriculus, which allowed a temporary bypass of the
dysfunctional esophagus until normal function and motility were regained. A crop
support pressure bandage was placed in 4 birds to improve crop emptying into the
proventriculus and to prevent crop distension. Although chelation therapy is the
gold standard treatment for lead toxicosis, severe cases of lead-induced crop
stasis are not acutely reversible with pharmaceuticals. In these condors,
placement of a feeding tube was deemed prudent to ensure a viable enteric route
of nutritional support during the standard treatment and recovery period in acute
lead toxicosis with crop stasis.
PMID- 23156981
TI - "Use of a locking compression plate as an external fixator for repair of a
tarsometatarsal fracture in a bald eagle (Haliaeetus leucocephalus)".
PMID- 23156982
TI - A few years out of veterinary school: are you happy as a veterinarian?
PMID- 23156983
TI - HPLC analysis and cytotoxic activity of Vernonia cinerea.
AB - The extracts of five Cambodian medicinal plants (Aganosma marginata, Dracaena
cambodiana, Harrisonia perforata, Hymenodictyon excelsum and Vernonia cinerea)
were evaluated in vitro for their cytotoxic activity against HT29 colon
adenocarcinoma cells and HepG2 hepatoma cells, using the MTT assay. Among these
five plants, Vernonia cinerea displayed potent cytotoxicity. One main
sesquiterpene lactone, 8alpha-tigloyloxy-hirsutinolide-13-O-acetate was isolated
from the whole plant of V. cinerea. This compound was active against both cancer
cell lines (IC50 = 3.50 microM for HT29 and IC50 = 4.27 microM for HepG2). To
quantify this compound in the plant, an analytical high-performance liquid
chromatography (HPLC) method was developed and validated.
PMID- 23156984
TI - Antiplasmodial activity of the ethnobotanical plant Cassia fistula.
AB - In our ongoing investigation of new compounds with activity against malaria
parasites, we tested the in vitro antiplasmodial activity of fractions and
purified compounds from Cassia fistula L., a plant traditionally used by native
populations of Tanzania, Zimbabwe, Mozambique and Brazil to treat malaria or
symptoms associated with this disease. Crude extracts from leaves, bark and
fruits were tested for their antiplasmodial activity against the chloroquine
sensitive strain of Plasmodium falciparum (D10), where leaf extracts showed the
highest activity. The chloroform extract of the leaves was further bioassay
guided fractionated using a combination of centrifugal partition chromatography
and flash column chromatography. Three main antiplasmodial principles, phytol (1)
(IC50 18.9 +/- 0.60 microM), lutein (2) (IC50 12.5 +/- 0.35 microM), and di
lineolylgalactopyranosyl-glycerol (DLGG) (IC50 5.8 +/- 0.27 microM) (3), were
isolated and identified using spectroscopic methods. When the three active
principles were tested for their cytotoxicity using a Chinese Hamster Ovarian
(CHO) cell line, compound 3 showed very weak toxicity (IC50 75.9 +/- 0.28
microM), while the other two compounds were nontoxic, even at the highest
concentration tested. The study provides evidence to support the use of Cassia
fistula as an antimalarial remedy and describes the antiplasmodial constituents
from the leaves.
PMID- 23156985
TI - Trichilone, a new C21 steroid from Trichilia connaroides.
AB - Phytochemical investigation of the leaves of Trichilia connaroides led to the
isolation of a new pregnane, trichilone (1), featuring a 2-methoxycyclopent-2
enone moiety, along with a related known compound, 3beta,4alpha-dihydroxypregnane
16-one (2). The structure of 1 was established on the basis of extensive
spectroscopic analysis. Compound 1 showed significant root-growth inhibition
activity against Amaranthus. mangostanus with an IC50 value of 23.1 ppm.
PMID- 23156986
TI - Three novel immunosuppressive steroidal glycosides from the stems of Stephanotis
mucronata.
AB - Three novel and one known C21 steroidal glycosides were isolated from the stems
of Stephanotis mucronata. Their structures were determined on the basis of
chemical evidence and extensive spectroscopic methods. The four C21 steroidal
glycosides displayed significant immunosuppressive activities in vitro.
PMID- 23156987
TI - Optimization of carbon source for hairy root growth and withaferin A and
withanone production in Withania somnifera.
AB - This study optimized carbon sources in half MS liquid medium for maximum biomass
accumulation and withanolides production in hairy root culture of Withania
somnifera. The highest production of withaferin A and withanone was achieved when
sucrose and sucrose+glucose were used individually as carbon sources. The hairy
root suspension culture supplemented with a lower level of sucrose (2%) favored
hairy root biomass accumulation (1.41 g DW) followed by sucrose+glucose (2+1)
when compared with other carbon sources in half MS liquid medium after 40 days of
culture. The hairy roots grown on sucrose (4%) enriched half MS liquid medium
stimulated higher production of withaferin A (2.21 mg/g DW) and withanone (2.41
mg/g DW) on the 40th day of culture, followed by sucrose+glucose (4+1%) compared
with glucose, fructose, maltose and other combinations tested.
PMID- 23156988
TI - Quantitative analysis of substituted N,N-dimethyl-tryptamines in the presence of
natural type XII alkaloids.
AB - This paper reports the qualitative and quantitative analysis (QA) of mixtures of
hallucinogens, N,N-dimethyltryptamine (DMT) (1), 5-methoxy- (la) and 5-hydroxy
N,N-dimethyltryptamine (1b) in the presence of beta-carbolines (indole alkaloids
of type XII) ((2), (3) and (5)}. The validated electronic absorption
spectroscopic (EAs) protocol achieved a concentration limit of detection (LOD) of
7.2.10(-7) mol/L {concentration limit of quantification (LOQ) of 24.10(-7) mol/L)
using bands (lambda max within 260+/-0.23-262+/-0.33 nm. Metrology, including
accuracy, measurement repeatability, measurement precision, trueness of
measurement, and reproducibility of the measurements are presented using N,N
dimethyltryptamine (DMA) as standard. The analytical quantities of mixtures of
alkaloids 4, 6 and 7 are: lambda max 317+/-0.45, 338+/-0.69 and 430+/-0.09 for 4
(LOD, 8.6.10(-7) mol/L; LOQ, 28.66(6), mol/L), as well as 528+/-0.75 nm for 6 and
7 (LOD, 8.2.10(-7) mol/L; LOQ, 27.33(3), mol/L), respectively. The partially
validated protocols by high performance liquid chromatography (HPLC),
electrospray ionization (ESI), mass spectrometry (MS), both in single and tandem
operation (MS/MS) mode, as well as matrix/assisted laser desorption/ionization
(MALDI) MS are elaborated. The Raman spectroscopic (RS) protocol for analysis of
psychoactive substances, characterized by strong fluorescence RS profile was
developed, with the detection limits being discussed. The known synergistic
effect leading to increase the psychoactive and hallucinogenic properties and the
reported acute poisoning cases from 1-7, make the present study emergent, since
as well the current lack of analytical data and the herein metrology obtained
contributed to the elaboration of highly selective and precise analytical
protocols, which would be of interest in the field of criminal forensic analysis.
PMID- 23156989
TI - HPLC analysis of stemokerrine and oxystemokerrine in the Thai medicinal plant
Stemona kerrii.
AB - A HPLC-UV method was developed and validated for determination of stemokerrine
and oxystemokerrine in Stemona kerrii roots. The chromatographic separation was
performed on a Hypersil BDS Cl8-column eluted with methanol: 50 mM ammonium
acetate solution using a gradient system with a flow rate of 1 mL/min and
detection at 300 nm. Stemokerrine and oxystemokerrine showed a linear
relationship within the range of 0.5-100 microg/mL. The method was shown to be
precise with a RSD <2%. The average percent recovery of stemokerrine was 101.6%
and for oxystemokerrine 99.5%. Two samples of S. kerrii were analyzed and the
average contents of stemokerrine and oxystemokerrine were 0.2 and 0.05%, w/w,
respectively. The present work will provide a useful standardization method for
S. kerrii raw materials for further pharmaceutical development.
PMID- 23156990
TI - Identification of pavinane alkaloids in the genera Argemone and Eschscholzia by
GC-MS.
AB - The genera Eschscholtzia and Argemone (Papaveraceae) represent a rich source of
pavinane alkaloids, the identification of which in alkaloid extracts is generally
problematic without standards. The alkaloid extracts of three Argemone and four
Eschscholtzia species were analyzed using GC-MS. The alkaloids were identified
based on comparison of their mass spectra with commercial libraries, with
reported data in the literature and with spectra of reference compounds. A total
of 23 alkaloids of six structural types (pavinane, protopine, benzylisoquinoline,
benzophenanthridine, aporphine and protoberberine) were identified. The
fragmentation pathway of pavinane alkaloids was used for their identification. O
Methylneocaryachine has been reported for the first time from a natural sources
and the alkaloid pattern of Eschscholzia pulchella has been analyzed and
described for the first time.
PMID- 23156991
TI - Effect of piperine on the pharmacokinetics and pharmacodynamics of glimepiride in
normal and streptozotocin-induced diabetic rats.
AB - The effect of piperine on the pharmacokinetics and pharmacodynamics of
glimepiride in normal as well as diabetic rats was studied. In normal and
streptozotocin induced diabetic rats the combination of glimepiride with piperine
increased all the pharmacokinetic parameters, such as Cmax, AUC0-n, AUCtotal,
t1/2, and MRT, and decreased the clearance, Vd, markedly as compared with the
control group. In pharmacodynamic studies, the combination of glimepiride with
piperine provided significant protection against the diabetes induced alterations
in the biochemical parameters. In addition, the combination of glimepiride with
piperine also improved the total antioxidant status significantly in diabetic
rats compared with piperine and glimepiride treated groups. The results revealed
that a combination of glimepiride with piperine led to the enhancement of the
bioavailability of glimepiride by inhibiting the CYP2C9 enzyme, which suggested
that piperine might be beneficial as an adjuvant to glimepiride in a proper dose,
in diabetic patients.
PMID- 23156992
TI - In silico prediction of the cosmetic whitening effects of naturally occurring
lead compounds.
AB - The identification of tyrosinase inhibitors is important, not only for the
treatment of skin hyperpigmentation disorders, such as melasma, but also for the
production of cosmetic whitening effects. The aim of this study was the in silico
prediction of the naturally occurring lead compounds in three commonly used skin
whitening herbs: Ampelopsis japonica, Lindera aggregata, and Ginkgo biloba. The
active ingredients responsible for the whitening effect of these herbs remain
largely unknown. The tyrosinase binding affinities and skin permeation, skin
irritancy, and corrosive properties of43 natural constituents of the three herbs
were predicted by docking simulations using Surflex-Dock and the QSAR-based
Dermal Permeability Coefficient Program (DERMWIN) and Skin Irritation Corrosion
Rules Estimation Tool (SICRET) implemented in Toxtree. Nine constituents of the
three herbs were found to have more advanced binding energies than the gold
standard whitening agents, arbutin and kojic acid, but 40 were indicative of at
least one skin sensitization alert, and many exhibited poor skin permeability.
Linderagalactone c and (+)-n-methyllaurotetanine were found to have the strongest
prospects for use in topical formulations, as they achieved high predicted
tyrosinase binding scores and displayed good skin permeation properties and
minimal potential for skin sensitization and irritation.
PMID- 23156993
TI - Profiling flavonoid cytotoxicity in human breast cancer cell lines: determination
of structure-function relationships.
AB - Flavonoids have been shown to be cytotoxic to cancer cells. However, the
mechanism of cytotoxicity has not been clearly defined. It has previously been
reported that HER2/ERBB2, the estrogen receptor, progesterone receptor, and p53
were required for flavonoid induced cytotoxicity in breast cancer cell lines. We
have used a panel of breast cancer cell lines, known to contain as well as be
deficient in these signaling pathways, to screen fourteen different flavonoids.
Comparing the cytotoxicity for all flavonoids allows us to determine if a
structure-functional relationship exists between cytotoxicity and flavonoid, and
if a particular signaling pathway is required for cytotoxicity. We show that
several flavonoids are cytotoxic to all cell lines including primary mammary
epithelial cells tested. The cytotoxic flavonoids are also able to inhibit
Mitochondrial Outer Membrane Permeability while at the same time stimulate ATP
levels whereas the non-cytotoxic flavonoids are not able to do this. We also show
that both cytotoxic and non-cytotoxic flavonoids can transverse the cell membrane
to enter MDA-MB-231 cells at different levels. Finally, all flavonoids regardless
of their cytotoxicity were able to induce some form of cell cycle arrest. We
conclude that for flavonoids to be strongly cytotoxic, they must possess the 2,3
double bond in the C-ring and we believe the cytotoxicity occurs through
mitochondrial poisoning in both cancer and normal cells.
PMID- 23156994
TI - Two new flavonoids from the seeds of Derris scandens.
AB - Two new flavonoids, (2S)-3',4',5'-trimethoxyflavanone (1) and 2'-hydroxy-2,4
dimethoxy-4'-O-[(E)-3,7-dimethyl-2,6-octadienyl]chalcone (2), together with a
known pterocarpene, flemichapparin B (3), and a known rotenoid, dehydrodeguelin
(4), were isolated from the seeds of Derris scandens. Their structures were
determined by means of extensive 1D and 2D NMR spectral studies.
PMID- 23156995
TI - Dihydroflavonol and flavonol derivatives from Macaranga recurvata.
AB - Two new dihydroflavonol derivatives, macarecurvatins A and B, have been isolated
from the leaves of Macaranga recurvata (Euphorbiaceaae), along with the known
compounds diisoprenylaromadendrin, glyasperin A and broussoflavonol F. The
structures of the new compounds were determined on the basis of spectroscopic
evidence. Upon cytotoxic evaluation against P-388 cells, macarecurvatin B showed
strong activity with an IC50 of 0.83 microM.
PMID- 23156996
TI - Flavonoids bearing an O-arabinofuranosyl-(1-->3)-rhamnoside moiety from
Cladocolea micrantha: inhibitory effect on human melanoma cells.
AB - Eleven known triterpenes (alpha-amyrin, beta-amyrin, lupeol, and their respective
acetates, 3-O-acetyl derivatives of betulinic, oleanolic, and ursolic acids,
cycloartenol, and tirucall-7,24-dienol), two new flavonols presenting an uncommon
interglycosidic O-(1-->3) linkage (kaempferol 3-O-alpha-L-arabinofuranosyl(1-->3)
alpha-L-rhamnoside and quercetin 3-O-alpha-L-arabinofuranosyl-(1-->3)-alpha-L
rhamnoside), beta-sitosterol, stigmasterol, quercetin, and gallic acid were
isolated from the Amazonian medicinal mistletoe, Cladocolea micrantha Kuijt
(Loranthaceae). Their structures were established by spectral methods and
eventual chromatographic comparisons. The quercetin derivative was not cytotoxic
to MV3 human melanoma cells, but was able, when administered at 1 microg/mL, to
promote a twofold inhibition of the migration of the cells through the transwell
system when compared with paclitaxel at 5 microM.
PMID- 23156997
TI - Effect of seasonality on chemical composition and antibacterial and anticandida
activities of Argentine propolis. Design of a topical formulation.
AB - The effect of seasonality on Argentine propolis collected during one year on its
phenolic and flavonoid content and on the growth of Gram-positive and Gram
negative antibiotic resistant bacteria and Candida species was evaluated.
Extracts of propolis samples collected in the summer and spring showed higher
phenolic and flavonoid contents than the samples collected in other seasons (5.86
to 6.06 mg GAE/mL and 3.77 to 4.23 mg QE/mL, respectively). The propolis
collected in summer and autumn showed higher antibacterial activity (30
microg/mL) than the other samples (MIC values between 30 and 120 microg/mL). No
antibacterial activity was detected against Gram-negative bacteria. Also, these
extracts were able to inhibit the development of five Candida species, with MFC
values of 15-120 microg/mL. Pharmaceutical formulations containing the more
active propolis extract were prepared. The hydrogel of acrylic acid polymer
containing summer propolis extract as an antimicrobial agent showed
microbiological, physical and functional stability during storage for 180 days.
The pharmaceutical preparation, as well as the propolis extracts, was active
against Candida sp. and antibiotic-multi-resistant Gram-positive bacteria. These
results reveal that propolis samples collected by scraping in four seasons,
especially in summer in Calingasta, San Juan, Argentina, can be used to obtain
tinctures and hydrogels with antibacterial and antimycotic potential for topical
use.
PMID- 23156998
TI - Larvicidal activity of isoflavonoids from Muellera frutescens extracts against
Aedes aegypti.
AB - The biological activity of extracts from the leaves, bark and roots of Muellera
frutescens, an Amazonian ichtyotoxic plant, were evaluated to find new
environmentally safe insecticides. The n-hexane extracts of bark, leaf, and root
showed a strong toxic activity against Aedes aegypti mosquito larvae. Bioguided
fractionation of the bark extract led to the isolation of seven isoflavonoids
(12a-hydroxyelliptone, elliptone, (-)-variabilin, rotenone, rotenolone, tephrosin
and deguelin). Rotenone and deguelin are responsible for the larvicidal activity
of the plant. M frutescens leaves contain up to 0.6%, w/w, deguelin. These
results justify the traditional ichtyotoxic use of M frutescens. The leaves
contain a relatively high proportion of deguelin and, therefore, can be
considered as a renewable source of this environmentally friendly insecticidal
isoflavonoid.
PMID- 23156999
TI - Phenolic compounds in five Epilobium species collected from Estonia.
AB - Epilobium species have been traditionally used as medicinal plants to treat
benign prostate hyperplasia. The present study investigated the content of
polyphenols, tannins, and flavonoids in Epilobium parviflorum Schreb., E.
hirsutum L., E. adenocaulon Hausskn., E. montanum L., and E. palustre L. growing
in Estonia. The total contents of polyphenols, tannins, and flavonoids were
studied using UV spectroscopy with subsequent HPLC quantification of gallic acid,
ellagic acid, and quercetin as marker compounds. All roots, stems, leaves, and
flowers of the plants investigated contained comparable amounts of polyphenols,
tannins, and flavonoids. There was a clear positive correlation between the
contents of tannins and flavonoids in various plant parts. The content of these
biologically active compounds suggests the use of E. parviflorum, E. hirsutum, E.
adenocaulon, E. montanum, and E. palustre collected from Estonia as herbs both
individually or as a blend.
PMID- 23157000
TI - A new prenylated acetophenone from the root bark of Derris indica.
AB - A new acetophenone, 1-[2,4-dihydroxy-5-(3-methylbut-2-enyl)phenyl]ethanone (1)
was isolated from the root bark of Derris indica, along with 3,7,-dimethoxy-3',4'
methylenedioxyflavone (desmethoxykanugin) (2), 5-methoxyfurano[4",5":6,7]flavone
(pinnatin) (3), and 3'-hydroxyfurano[4",5":7,8]flavone (pongol) (4). The
structures of these compounds were established by means of chemical and spectral
studies. The occurrence of this prenylated acetophenone in D. indica is of
biogenetic and chemotaxonomic significance.
PMID- 23157001
TI - Phytotoxic furanocoumarins from the shoots of Semenovia transiliensis.
AB - Discovery of novel, natural herbicides has become important to manage increasing
weed resistance to synthetic herbicides and environmental issues. The systematic
bioassay-guided fractionation and purification of the methylene chloride/methanol
extract of the shoots of Semenovia transiliensis led to the isolation of several
phytotoxic compounds. Lactuca sativa L. (lettuce, a dicot) and Agrostis
stolonifera L. (bentgrass, a monocot) bioassays were used to identify and isolate
the phytotoxic fractions. A number of furanocoumarin compounds isolated from S.
transiliensis shoots were phytotoxic to both test species. These included
psoralen, isopsoralen, heratomin, isopentenyloxyisobergapten, imperatorin,
bergapten, xanthotoxin, heraclenin, and heraclenol. All the active secondary
metabolites isolated from the shoots of S. transiliensis were furanocoumarins.
Identification of these was accomplished using mass spectrometry and 1- and 2
dimensional NMR techniques. Phytotoxic activity o f isolated compounds w a s
evaluated in a dose-response manner from 0.3 to 1000 microM. Ingeneral, all of
the compounds were more active on A. stolonifera than L. sativa. Bergaptin and
xanthotoxin were the most active of the compounds, with moderate activity at 100
microM. Imperatorin and xanthotoxin inhibited growth of Lemna paucicostata
Hegelm. by 50% at 29 and 60 microM, respectively. Our results show that S.
transiliensis is rich in furanocoumarins, which are probably involved in various
aspects of the chemical ecology of the species. Unfortunately, the general
cytotoxicity of furanocoumarins makes them an unlikely candidate for pesticide
discovery.
PMID- 23157002
TI - Chemoenzymatic synthesis of two new halogenated coumarin glycosides as potential
antifungal agents.
AB - Two new potential antifungal coumarin glycosides, 6-chlorocoumarin 7-O-beta-D
glucopyranoside (1) and 7-hydroxy-4-trifluoromethyl-coumarin 5-O-beta-D
glucopyranoside (2), were synthesized via enzyme-mediated glycosylation of the
respective aglycone, 6-chloro-7-hydroxycoumarin and 5,7-dihydroxy-4
trifluoromethylcoumarin, using transgenic hairy roots of Polygonum multiflorum.
Instead of application of the isolated enzyme and exogenous sugar donors, hairy
roots of P. multiflorum were successfully adapted as a whole-cell biocatalyst.
PMID- 23157003
TI - Two new naphthoquinone derivatives from the stem bark of Callicarpa maingayi.
AB - Two new naphthoquinones designated as 3alpha-hydroxy-2-(2-hydroxypropan-2-yI)
9alpha-methoxy-2,3,3alpha,9alpha-tetra-hydronaphtho[2,3-b]furan-4,9-dione
(callicarpa-quinone A, 1) and 5-hydroxy-2-(2-hydroxypropan-2-yl)naphtho[2,3
b]furan-4,9-dione (callicarpaquinone B, 2) were isolated from the chloroform
fraction of Callicarpa maingayi. Three other known compounds, identified as
avicequinone-C (3), wodeshiol (4) and paulownin (5), were reported for the first
time from this species. The structure elucidation of compounds was established by
comprehensive 1D and 2D NMR spectroscopic analyses as well as EIMS, UV and IR
spectral data. Compounds 1 and 2 were tested in vitro for their cytotoxic
activity against human breast cancer MCF-7cells. Compound 2 exhibited strong
cytotoxic activity with an IC50 value of 1.9 +/- 0.2 microM, while 1 showed
moderate activity with an IC50 value of 25.0 +/- 4.3 microM.
PMID- 23157004
TI - Novel sorbicillin analogues from the marine fungus Trichoderma sp. associated
with the seastar Acanthaster planci.
AB - Two novel sorbicillinoid analogues, (4'Z)-sorbicillin (1) and (2S)-2,3-dihydro-7
hydroxy-6-methyl-2-[(E)-prop-1-enyl]-chroman-4-one (2), together with three known
compounds, (2S)-2,3-dihydro-7-hydroxy-6,8-dimethyl-2-[(E)-prop-1-enyl]-chroman-4
one (3), sorbicillin (4), and 2',3'-dihydrosorbicillin (5), were isolated from
the culture broth of the fungus Trichoderma sp. associated with the seastar
Acanthaster planci. Their structures were determined by analysis of the NMR and
MS data. Compound I was the first example with a Z-configuration of the C-4'/C-5'
double bond in the sorbyl side chain. Compounds 2 and 3 were uncommon monomeric
sorbicillinoids with a cyclic sorbyl chain. 2, 3 and 5 showed moderate cytotoxic
activities against various cancer cell lines.
PMID- 23157005
TI - Cytotoxic bioactivity of some phenylpropanoic acid derivatives.
AB - In this study, we synthesized a series of phenylpropanoic acid derivatives based
on modifications at four selected points of the molecular scaffold. The in vitro
antiproliferative activities of the compounds were examined in representative
human solid tumor cell lines. A SAR was established pointing out the relevance of
the substituents. The best activity profiles were obtained for the derivatives
bearing more lipophilic esters (GI50 3.1-21 microM).
PMID- 23157006
TI - Anti-Helicobacter pylori activities of natural isopentenyloxycinnamyl derivatives
from Boronia pinnata.
AB - In this study we investigated the anti-Helicobacter pylori activity of four
isopentenyloxycinnamyl derivatives from the Australian shrub Boronia pinnata Sm.
(Rutaceae), structurally related to boropinic acid: (E)-3-(4-(3-methylbut-2
enyloxy)-3,5-dimethoxyphenyl)acrylaldehyde (1), boropinol C (2), boropinal (3)
and boropinol A (4). In vitro growth of H. pylori strains 26695 and B128 was
analyzed in liquid culture with increasing doses of these compounds. Bacterial
morphology was visualized by scanning electron microscopy. The in vivo effects of
the two most efficient molecules that reduced bacterial growth in vitro,
compounds 3 and 4, were investigated on H. pylori gastric colonization in the
mouse model. The presence of these compounds in the bacterial cultures led to
alterations of bacterial surface and flagella. In vivo, both compounds 3 and 4 at
250 microM reduced significantly the ability of H pylori to colonize the gastric
mucosa of mice, compared with untreated ones. These data indicate that these
natural isopentenyloxycinnamyl derivatives related to boropinic acid can be
considered as novel antibacterial agents with anti-H. pylori activity.
PMID- 23157007
TI - Thymofolinoates A and B, new cinnamic acid derivatives from Euphorbia thymifolia.
AB - Two new cinnamic acid derivatives, thymofolinoates A (1) and B (2) have been
isolated from the chloroform soluble fraction of Euphorbia thymifolia and their
structures assigned from 1H and 13C NMR spectra, DEPT and by 2 D COSY, HMQCand H
MBC experiments. In addition, p-hydroxy cinnamic acid(3), 5-hydroxy-6,7,8,4'
tetramethoxy flavone (4), and 5-hydroxy-3',4',6,7,8-pentamethoxy flavone (5) have
also been isolated for the first time from this species.
PMID- 23157008
TI - Efficient counter-current chromatographic isolation and structural identification
of two new cinnamic acids from Echinacea purpurea.
AB - Two new cinnamic acids, 2-O-caffeoyl-3-O-isoferuloyltartaric (3), and 2, 3-di-O
isoferuloyltartaric acid (5), along with three known caffeic acids, cichoric acid
(1), 2-O-caffeoyl-3-O-feruloyltartaric acid (2) and 2-O-caffeoyl-3-O-p
coumaroyltartaric acid (4), have been successfully isolated and purified from
Echinacea purpurea. In this study, we investigated an efficient method for the
preparative isolation and purification of cinnamic acids from E. purpurea by high
speed counter-current chromatography (HSCCC). The separation was performed using
a two-phase solvent composed of n-hexane-ethyl-acetate-methanol-0.5% aqueous
acetic acid (1:3:1:4, v/v). The upper phase was used as the stationary phase and
the lower phase as the mobile phase, with a flow rate of 1.6 mL/min. From 250 mg
of crude extracts, 65.1 mg of 1, 8.3 mg of 2, 4.0 mg of 3, 4.5 mg of 4, and 4.3
mg of 5 were isolated in one-step, with purities of 98.5%, 97.7%, 94.6%, 94.3%,
and 98.6%, respectively, as evaluated by HPLC-DAD. The chemical structures were
identified by electro spray ionization mass spectrometry (ESI-MS) and one- and
two-dimensional NMR spectra. HSCCC was very efficient for the separation and
purification of the cinnamic acids from
PMID- 23157009
TI - Norlignans from Asparagus cochinchinensis.
AB - A new norlignan glycoside, named iso-agatharesinoside (2), and its aglycone, iso
agatharesinol (1), were isolated from the tuberous roots of Asparagus
cochinchinensis. Their structures were established on the basis of spectral data,
particularly by the use of 1D NMR and several 2D shift-correlated NMR pulse
sequences (1H-1H COSY, HSQC, HMBC and ROESY).
PMID- 23157010
TI - Novel application of Mahua (Madhuca sp.) flowers for augmented protease
production from Aeromonas sp. S1.
AB - The present study explored the utilization of Mahua (Madhuca sp.) flowers, a
major non-timber forest product (NTFP) of India, as a low-cost, natural substrate
for protease production under submerged fermentation. Bacterial strain Aeromonas
sp. Si1, previously reported by us, was used as the protease producer. Using
Mahua flower extract (MFE) as the medium additive, the protease production could
successfully be enhanced by 5.6-fold (564.5 UmL-1) after 24 h of fermentation
under optimized conditions compared with initial production of 99.9 UmL' in the
absence of MFE. The cultural parameters for optimum production of protease were
determined to be: incubation time-24 h; pH-7.0; MFE concentration-5% (v/v);
inoculum size-0.3% (v/v) and agitation rate-200 rpm. The results obtained
demonstrate the potential of cheaper and abundantly available Mahua flowers for
induction of proteases, and thus offer a new approach for value addition to this
biomass through industrial enzyme production.
PMID- 23157011
TI - Chemical composition of the fatty oils of the seeds of Cleome viscosa accessions.
AB - Fatty oils of the seeds of Cleome viscosa accessions from Delhi, Jaipur,
Faridabad, Surajkund and Hyderabad were methylated and analyzed by GC and GC
MS.The major fatty acids, identified as their methyl esters, of the oils from
these five locations were palmitic acid (10.2-13.4%), stearic acid (7.2-10.2%),
oleic acid (16.9-27.1%) and linoleic acid (47.0-61.1%). In addition, palmitoleic
acid,octadec-(11E)-enoicacid, arachidic acid, eicosa-(11Z)-enoic acid, linolenic
acid, heneicosanoic acid, behenic acid, lignoceric acid, pentacosanoic acid,
hexacosanoic acid, 12-oxo-stearic acid, and the alkanes tetracosane, pentacosane,
hexacosane, heptacosane, octacosane, nonacosane, triocontane, hentriacontane and
dotriacontane, were also identified as minor and trace constituents in some of
these oils.
PMID- 23157012
TI - Essential oil and other constituents from Magnolia ovata fruit.
AB - The volatile and non-volatile constituents of the unripe fruits of Magnolia ovata
(A. St.-Hil.) Spreng. (Magnoliaceae) were studied. The essential oils were
obtained by hydrodistillation of the fruit of two plant populations (A and B) and
analyzed by GC/FID and GC/MS. The oil of sample A was rich in sesquiterpenes,
mainly spathulenol (19.3%), while the oil of sample B showed a predominance of
aliphatic compounds, mainly hexadecanoic acid (52.0%). Extracts of the dried
fruit contained fourteen known compounds including nine lignoids (magnovatin A,
magnovatin B, acuminatin, licarin A, oleiferin A, oleiferin C, kadsurenin M, 4-O
demethylkadsurenim M and 7-epi-virolin), two sesquiterpene lactones (parthenolide
and michelenolide) and three alkaloids (lysicamine, lanuginosine and O
methylmoschatoline). Michelenolide, 7-epi-virolin and lisycamine are reported for
the first time in the species, while the remaining compounds have already been
reported in the leaves and/or trunk bark o f Magnolia ovata. Acetylation o f
oleiferin A yielded a ne wcompound, acetyl oleiferin A, whose NMR data and that
of michelenolide are furnished.
PMID- 23157013
TI - Chemical composition of the essential oil of Zingiber zerumbet var. darcyi.
AB - The chemical composition of essential oil obtained by hydrodistillation method
from the rhizomes of Z. zerumbet var. darcyi was determined by GC and GC-MS.
Thirty-three compounds, accounting for 93.6% of the oil were identified including
twenty compounds in minor (0.1-0.6%) and eight in trace (<0.05%) amounts. The
main compounds were zerumbone (69.9%) alpha-humulene (12.9%), humulene epoxide II
(2.5%), caryophyllene oxide (1.1%) and camphene (1.9%). In this analysis, it has
been found that the variety could be used as an additional new source of natural
zerumbone besides Zingiber zerumbet. This is a first report on the analysis of Z.
zerumbet var. darcyi oil.
PMID- 23157014
TI - Compositions of the volatile oils of Citrus macroptera and C. maxima.
AB - The essential oils obtained by hydrodistillation from the fresh peels of Citrus
macroptera Montr. and C. maxima (Burm.) Merr. were analyzed by GC and GC/MS. The
yields of oil ranged from 0.53% in C. macroptera to 0.13% in C. maxima cultivar
(white). Forty-seven compounds were identified in the oils with limonene (55.3
80.0%), dodecyl acrylate (2.2-8.0%), geranial (0.4-3.5%), trans-linalool oxide
(1.0-2.8%), alpha-terpineol (0.7-2.3%), linalool (0.7-1.5%) and cis-linalool
oxide (0.5-1.4%) identified as major compounds. The oil ofC. macroptera contained
limonene (55.3%), beta-caryophyllene (4.7%) and geranial (3.5%) as main
compounds. Similarly, oils from two C. maxima (pink and white) cultivars were
rich in limonene (72.0-80.0%), dodecyl acrylate (8.0-7.2%) and nootkatone (1.6
2.5%). C. maxima (pink and white) cultivars were found to contain higher amount
of limonene (72.0 and 80.0%) as compared with C. macroptera (55.3%). The chemical
compositions of the oils were found to be similar, but nootkatone (1.6-2.5%) was
identified only in C. maxima cultivars.
PMID- 23157015
TI - Chemotaxonomical markers in essential oil of Murraya koenigii.
AB - The composition of the essential oils of Murraya koenigii (L.) Spreng, cultivated
at six locations in Peninsula Malaysia and Borneo are presented. The oils were
obtained from fresh leaves by hydrodistillation and analyzed by gas
chromatography-mass spectrometry (GC-MS); 61 compounds were identified, of which
eleven were present in all the specimens analyzed. The two major volatile
metabolites were identified as beta-caryophyllene (16.6-26.6%) and alpha-humulene
(15.2-26.7%) along with nine minor compounds identified as beta-elemene (0.3
1.3%), aromadendrene (0.5-1.5%), beta-selinene (3.8-6.5%), spathulenol (0.6
2.7%), caryophyllene oxide (0.7-3.6%), viridiflorol (1.5-5.5%), 2
naphthalenemethanol (0.7-4.8%), trivertal (0.1-1.0%) and juniper camphor (2.6
8.3%). The results suggest that beta-caryophyllene and alpha-humulene could be
used as chemotaxonomical markers for Malaysian M. koenigii, hence these specimens
could be of the same stock and different from the ones in India, Thailand and
China.
PMID- 23157016
TI - Essential oil composition and antibacterial activity of Anthemis mixta and A.
tomentosa (Asteraceae).
AB - In the present study the chemical composition of the essential oils from aerial
parts and roots of Anthemis mixta L. and A. tomentosa L. was evaluated by GC and
GC-MS, and their antibacterial activity tested against ten bacterial species.
Hexadecanoic acid (15.2%) was recognized as the main constituent ofA. mixta,
together with tau-cadinol (6.7%), while in both aerial parts and roots of A.
tomentosa nonacosane (21.9% and 20.7%), heptacosane (8.1% and 6.0%), hexadecanoic
acid (8.1% and 27.1%) and hexahydrofarnesylacetone (6.8% and 5.5%) prevailed. The
oils from aerial parts of both species showed a good activity against Gram
positive bacteria. These results suggest that the plants could be potentially
used in food manufacture and cosmetology as preservative agents or in medicine as
new antibiotics.
PMID- 23157017
TI - Antifungal and antibacterial activity of the essential oil of Chamaecyparis
lawsoniana from Spain.
AB - The essential oils extracted from the young stems and leaves of Chamaecyparis
lawsoniana (A.Murray) Parl. have been analysed by Gas Chromatography and Gas
Chromatography coupled to Mass Spectrometry. A total of 66 compounds were
identified representing around the 99% of the total oil. The oil was richer in
monoterpenes than in sesquiterpenes. The only main component was limonene with a
percentage composition of 77.7%. The rest of compounds that contribute to the
fragrance had percentage composition lower that the 3.0%: p-cymen-7-ol (3.0%),
myrcene (2.4%), camphor (2.1%), delta-elemene (1.6%), oplopanonyl acetate (1.6%),
methyl perillate (1.3%), terpinen-4-ol (1.0%) and beta-oplopenone 1.0%. The
antibacterial and antifungal activity of this oil was also tested against
different microorganisms. The only fungus tested, Candida albicans, was very
sensitive to the treatment with an inhibition halos of 20mm. The oil was more
effective with the Gram (+) than with Gram (-) bacteria. The inhibition halos
were 12mm, 12-13mm and 12-13mm for Bacillus subtilis, Staphylococcus aureus and
Micrococcus luteus respectively. We report new data of the antibacterial and
antifungal activity of the essential oil of this species. The essential oil of C.
lawsoniana could be considered as a good natural antibacterial and antifungal
agent.
PMID- 23157018
TI - Chemical composition and biological activities of essential oil from Hyptis
crenata growing in the Brazilian cerrado.
AB - Essential oils from species of the genus Hyptis are well-known for their
significant biological properties, including antimicrobial and acaricidal
activities. The essential oil from the aerial parts of H. crenata was obtained by
hydrodistillation; bomeol (17.8%), 1,8-cineol (15.6%) and p-cimene (7.9%) were
characterized by GC-MS as its major constituents. The essential oil was evaluated
in vitro for its antimicrobial activities against six fungal and five bacterial
strains, by measuring the respective MICs, MFCs and MBCs, using broth
microdilution methods. The strongest bactericidal activities were shown against
Staphylococcus aureus and Enterococcus faecalis, while the strongest fungicidal
activities were against Cryptococcus neoformans, Candida glabrata and Candida
tropicalis. The oil was also assessed for its anti-tick properties and, at a
concentration of 2.5%, it significantly inhibited in vivo oviposition of engorged
females of the cattle tick Rhipicephalus (Boophilus) microplus, using the adult
immersion test., with an effectiveness of 94.4%.
PMID- 23157019
TI - Larvicidal activity against Aedes aegypti of essential oils from northeast
Brazil.
AB - The larvicidal activities of essential oils from the leaves of Artemisia vulgaris
L., Cymbopogon flexuosus (Nees ex Steud.) Wats. and Piper tuberculatum Jacq. were
evaluated using third-instar larvae of Aedes aegypti. The essential oils were
obtained by hydrodistillation and analyzed by GC and GC-MS. The essential oil of
P. tuberculqatum had the lowest LC50 value (106.3 +/- 2.2 microg/mL), followed by
that of A. vulgaris (114.1 +/- 1.7 microg/mL) and C. flexuosus (121.6 +/- 0.8
micro/mL). The results show that these essential oils may be potent sources of
natural larvicides.
PMID- 23157020
TI - Composition and antipseudomonal effect of essential oils isolated from different
lavender species.
AB - The aims of our research include the phytochemical characterization of the
essential oils extracted from different lavender species (Lavandula vera L., L.
intermedia L., L. pyrenaica DC., and L. stoechas subsp. stoechas) that are
important from therapeutic and economic aspects, as well as the optimization of
the tube dilution method for microbiological investigation of the effect of
essential oils on the selected Pseudomonas strain. The chemical and percentage
compositions of the essential oils were analysed by gas chromatography (GC) and
gas chromatography-mass spectrometry (GC-MS). The main component of the essential
oils in the majority of lavender species was linalool, while L-fencone was
identified in the largest amount in L. stoechas subsp. stoechas. Tube dilution is
one of the most frequently used methods for microbiological investigation. Its
advantages are that it is easy to perform and provides information about minimum
bactericidal concentration (MBC). Because of the lipophilic character of
essential oils, the tube dilution method should be optimized for the detection of
antibacterial activity of these plant extracts, and, therefore, emulsions
containing 0.2% polysorbate 80 were prepared from the samples. In each of the
eight investigated essential oils an inhibitory effect was detected, and MBC
values were in the range 12.5-50 microL/mL in seven cases.
PMID- 23157022
TI - Antimicrobial activity of blended essential oil preparation.
AB - Antimicrobial activities of two blended essential oil preparations comprising
lavender oil, petigrain oil, clary sage oil, ylang ylang oil and jasmine oil were
evaluated against various pathogenic microorganisms. Both preparations showed
antimicrobial activity in the agar disc diffusion assay against the Gram-positive
bacteria, Staphylococcus aureus ATCC6538 and S. epidermidis isolated strain, the
fungus, Candida albicans ATCC10231, and the Gram-negative bacterium, Escherichia
coli ATCC25922, but showed no activity against Pseudomonas aeruginosa ATCC9027.
The minimum inhibitory concentration (MIC) of these preparations was evaluated.
By the broth microdilution assay, preparation 1, comprising lavender oil, clary
sage oil, and ylang ylang oil (volume ratio 3:4:3), exhibited stronger
antimicrobial activity than preparation 2, which was composed of petigrain oil,
clary sage oil, and jasmine oil (volume ratio 3:4:3). Moreover, the sum of the
fractional inhibitory concentrations (Sigma fic) of preparation 1 expressed a
synergistic antimicrobial effect against the tested microorganisms (Sigma fic